Chinese medicinal herbs for the common cold

Abstract

Background

Chinese medicinal herbs are frequently used to treat the common cold in China. Until now, their efficacy has not been systematically reviewed.

Objectives

To assess the effectiveness and safety of Chinese medicinal herbs for the common cold.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, issue 2), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register; MEDLINE (1966 to May 2008); EMBASE (1980 to May 2008); AMED (1985 to May 2008); the Chinese Biomedical Database (CBMdisc) (1978 to May 2008); and China National Knowledge Infrastructure (CNKI) (1994 to May 2008).

Selection criteria

Randomised controlled trials (RCTs) studying the efficacy of Chinese medicinal herb(s) for the treatment of the common cold.

Data collection and analysis

Four review authors telephoned the original trial authors of the RCTs identified by our searches to verify the randomisation procedure. Two review authors extracted and analysed data from trials which met the inclusion criteria.

Main results

We found17 studies involving 3212 patients. The methods of 15 studies were at high risk of bias. In only two studies was the risk of bias low. Trials used "positive drugs", of which the efficacy was not known, as controls. Different Chinese herbal preparations were tested in nearly all trials. In only one trial was a Chinese herbal preparation tested twice. In seven trials, six herbal preparations were found to be more effective at enhancing recovery than the control preparations. In the other 10 studies, seven herbal preparations were not shown to be significantly different from the control. One study did not describe the difference between the intervention and control groups.

Authors' conclusions

Chinese herbal medicines may shorten the symptomatic phase in patients with the common cold. However, the lack of trials of low enough risk of bias, or using a placebo or a drug clearly identified as a control, means that we are uncertain enough to be unable to recommend any kind of Chinese medicinal herbs for the common cold.

Plain language summary

Chinese medicinal herbs to treat the common cold

The common cold is the most widespread acute respiratory tract illness affecting all age groups. Many Chinese herbal medicines are used to treat this illness in China. Although we included 17 trials, involving 3212 patients, in this review, the risk of bias was so high that the evidence did not support using any Chinese herbal preparation(s) for the common cold. Well‐designed clinical trials are required.

Background

Description of the condition

The common cold is the most widespread acute respiratory tract illness across all age groups. Young children suffer an average of six to eight colds per year, and adults an average of two to four colds per year (ALA 2003; Kotton 2003). Colds are defined by the presence of a typical set of symptoms, but can be caused by more than 200 different viruses (Kotton 2003). Although the common cold is a mild and self‐limiting illness, it can lead to complications if effective treatment is not commenced early enough. Some cases can lead to serious ear or sinus infections or may develop into pneumonia. Complications such as myocarditis or other connective tissue disorders can also occur.

Symptoms of the common cold typically include a runny nose, congestion, sneezing, weakened sense of taste and smell, scratchy throat and cough. These start developing in the first three days following infection. Infants and young children are more likely than adults and teens to also develop fever. Symptoms usually abate within seven to 10 days but some colds last longer, especially in children, the elderly and those with generally poor health (ALA 2003; Kotton 2003).

Description of the intervention

Treatment by a health care provider is not necessary. Symptoms may be treated in a variety of ways, including combination decongestant/antihistamines, warm salt gargles, lozenges and cough suppressants with dextromethorphan or codeine, or sipping hot chicken soup to increase the clearance of nasal mucous (Kotton 2003).

Other Cochrane Reviews have published important findings in relation to treatment options for the common cold. The available evidence does not support the use of high doses of vitamin C for treating the common cold (Douglas 2004). Likewise, there is insufficient evidence to support the treatment of upper respiratory tract infections with antibiotics, and an increased risk of adverse effects associated with antibiotic use in adult patients (Arroll 2005). Marshall 1999 found that treatment with zinc lozenges did not reduce the duration of cold symptoms. Antihistamines alone do not alleviate nasal congestion, rhinorrhoea and sneezing, or subjective improvement of the common cold in either children or adults (De Sutter 2003). Antihistamines cause adverse effects, especially sedation. Combinations of antihistamines with decongestants have been found to be ineffective in young children. It is unclear whether the effects on general recovery or nasal symptoms are clinically significant in older children and adults (De Sutter 2003). There are no effective licensed antiviral drugs for the common cold (Jefferson 2002).

Many Chinese physicians believe that herbal medicines are effective in alleviating symptoms and shortening the duration of the common cold. Chinese herbal medicines are routinely used for most respiratory diseases in hospitals and by many Chinese people at home.

Chinese traditional medicine follows a particular theoretical and methodological pathway which assesses the cause, leading to diagnosis and treatment. Colds are categorised according to the different causes and symptoms, for example 'chills cold' and 'fever cold'. A 'chills cold' is so classified because the patients themselves feel cold and chilly; they also experience nasal obstruction, do not sweat, generally have a high temperature, develop a thin, white fur on the tongue, and experience a productive cough. 'Fever cold', on the other hand, is defined by the fact that patients do not feel chilly, have an elevated temperature, develop a thin and slightly yellow fur on the tongue, and experience a productive cough.

Herbs are indicated and dispensed in accordance with the symptoms or causes of the cold. For example Shi Gao (Gypsum Fibrosum) compounds can markedly abate fever (Deng 1998a), and Chai Hu (Bupleurum chinesenes DC) and Jing Jie (Herba Schizonepetae) act as analgesics (Wang 1998; Xu 1998). Ma Huang (Herba Ephedrae) can be used to induce perspiration and as an analgesic (Gong 1998); while Ban Xia (Rhizoma Pinelliae) is dispensed to loosen sputum and suppress coughs (Xue 1998). Fang Feng (Radix Saposhnikiviae) and Zhi Shu Ye (Folium Perillae) are given for what is commonly termed 'chill cough'; Jin Ying Hua (Flos Lonicerae) and Bo He (Herba Menthae) for 'fever cough'; and Fructus Gardeniae for fever and convulsions.

Why it is important to do this review

Modern pharmacological experiments demonstrate that some herbs, such as Jin Ying Hua (Flos Lonicerae) (Deng 1998b), Yu Xin Chao (Herba Houttuyniae) (Deng 1998c), and Ban Lan Gen (Radix Isatidis) (Deng 1998d) do have antiviral or antibacterial functions. The principles of traditional Chinese medicine (TCM) state that the ideal effect will result from using Chinese medicinal herbs according to its guidelines. Using the herbs incorrectly may cause harm rather than benefit; for example, the herbs for 'fever cold' should never be used for a 'chills cold'.

In China, more than 100 varieties of herbal preparation are used in the prevention and treatment of the common cold. Hundreds of millions of dollars are spent on treating colds each year (Zuo 2006). Hundreds of clinical studies have been carried out on Chinese medicinal herbs for the common cold. These include five randomised controlled trials (RCTs) involving 880 participants conducted on "Huang Zhi Hua oral preparation" (Cheng 1999; He 1999; Pan 1999; Wang 1999a; Yi 1999a). Almost all of these studies have reported a positive effect.

In high‐income countries there is increasing public interest in, and use of, a wide range of therapies which lie outside the 'mainstream' or traditional Western medical practice. The recent House of Lords Select Committee report on Complementary and Alternative Medicine (CAM) heard that "we are now experiencing a rapid increase in the use of CAM across the Western World" (HLSC 2000). Whether we support or criticise their effectiveness, herbal medicines are widely used.

There is evidence to indicate that not all herbs are risk‐free. There are concerns about adverse events, including allergic reactions and Chinese herbal nephropathy (CHN) (Lampert 2002; Lord 2001; Nortier 2000). Scientific evidence which indicates that Chinese herbal medicines are more effective than antibiotics in the treatment of acute respiratory infections is insufficient (Liu 1998).

Objectives

To assess the efficacy and safety of Chinese medicinal herbs for the treatment of the common cold in children and adults.

Secondary objectives were to compare the efficacy of different Chinese medicinal herbs and record any related adverse events.

When making comparisons between groups intended for treatment with Chinese medicinal herbs and groups allocated to the placebo or other current treatment regimes, or various Chinese medicinal herbs, we tested the following hypotheses:

1. that there is no difference in the number of people cured by the end of the third day; and

2. that there is no difference in the number of adverse events.

Methods

Criteria for considering studies for this review

Types of studies

Randomised controlled trials (RCTs) studying the efficacy of Chinese medicinal herbs for the common cold. If trials did not report the outcome we were looking for, we contacted the trial authors to ask for this additional information; the trials were excluded if this information was not available.

Types of participants

Children (17 years or younger) and adults (18 years or older) with the common cold.

The common cold is defined as acute inflammation of the nasal cavity, pharynx or larynx, caused by viral infection(s). Typical symptoms include runny nose, nasal congestion, sneezing, sore or scratchy throat, cough, fatigue and fever. Ideally, the diagnostic criteria for the common cold should be described in the trial. To allow for changes in classification and diagnostic criteria of the disease, the diagnosis should be established using the standard criteria valid at the time of conducting the trial. Changes in diagnostic criteria may have produced variability in the clinical characteristics of the patients included and the results obtained. We considered, documented and explored these changes in a sensitivity analysis.

We excluded colds caused by influenza in this review ‐ symptoms always included headache, muscle ache and fatigue, high fever, usually a cough, sometimes a runny nose, sneezing, sore throat, and itching eyes, nose, or throat. We also excluded acute bronchitis developing from a case of common cold. These illnesses are assessed in other Cochrane Reviews (Chen 2005; Wei 2005).

We excluded patients concurrently suffering from other infectious or febrile diseases, or both.

Types of interventions

Chinese herbal medicines compared with placebo or other treatments for the common cold. We excluded prohibited or suspended Chinese herbal preparations.

Types of outcome measures

Primary outcomes

Recovery refers to whether the symptoms of common cold were cleared within three days after treatment. Trials use the following outcome measures:

1. 'fast effect' ‐ which means that the fever abated within two to four hours after treatment, with symptoms subsiding after 24 hours. This was considered as a 'recovery';

2. 'marked effect' ‐ which means that the fever abated within 24 to 48 hours after treatment, with symptoms of the common cold subsiding after 48 hours. This was also considered as a 'recovery'.

Secondary outcomes

1. Fever clearance time: fever clearance time refers to the time between commencing treatment and temperature returning to normal.

2. Improvement: temperature returns to normal and most of the symptoms disappear within three days of administration of the Chinese herbal preparation.

3. Partial improvement: fever abatement and some symptoms disappear within three days of administration of the Chinese herbal preparation.

4. No improvement: no significant change in symptoms was noted at the end of the third day following the administration of the Chinese herbal preparation. Patients with a high fever treated with physiotherapy or antibiotics (for clearance of fever during the treatment) were considered in this category.

5. Adverse events: we defined serious adverse events according to the ICH Guidelines (ICHEWG 1997) as any event that leads to death, is life‐threatening, requires inpatient hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability, and any important medical event which may have jeopardised the patient or required intervention to prevent it. We considered all other adverse events to be non‐serious.

6. Additional outcomes: we attempted to analyse the effects of the interventions on TCM signs, which follow a particular theoretical and methodological pathway, as additional outcomes in this review. See the final point in the Discussion section with regards to validating methods used to measure TCM signs.

Search methods for identification of studies

Electronic searches

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, issue 2) which contains the Cochrane Acute Respiratory Infections Group's Specialised Register; MEDLINE (1966 to May 2008); EMBASE (1980 to May 2008); AMED (1985 to May 2008); the Chinese Biomedical Database (CBMdisc) (1978 to May 2008); and China National Knowledge Infrastructure (CNKI) (1994 to May 2008).

The MEDLINE search strategy is shown below. We combined the MEDLINE search string with the highly sensitive search strategy (Dickersin 1994). See Appendix 1 for the CENTRAL search strategy. The search string was adapted for EMBASE, AMED, the Chinese Biomedical Database and China National Knowledge Infrastructure.

MEDLINE (Ovid)

1 exp Common cold/ 
 2 common cold.mp. 
 3 exp Rhinovirus/ 
 4 rhinovirus$.mp. 
 5 (upper respiratory tract infection$ or URTI).mp. 
 6 (upper respiratory infection$ or URI).mp. 
 7 or/1‐6 
 8 exp Medicine, Chinese Traditional/ 
 9 exp Drugs, Chinese Herbal/ 
 10 herbal medic$.mp. 
 11 medicinal herb$.mp. 
 12 chinese herb$.mp. 
 13 chinese medic$.mp. 
 14 or/8‐13 
 15 7 and 14

Searching other resources

We checked the references of published studies to identify additional trials. We contacted trial authors to identify any unpublished papers, but could not contact pharmaceutical companies who produced relevant products. There were no language or publication restrictions.

We also searched for ongoing trials in:

1. National Research Register (http://www.nrr.nhs.uk/);

2. Cancer Clinical Trial Register (http://www.qldcancer.com.au/Research/SubmissionForm.html);

3. Current Controlled Trials (http://www.controlled‐trials.com/);

4. Chinese Clinical Trial Register (http://www.chictr.org);

5. Australian Clinical Trial Registry (http://www.actr.org.au/); and

6. WHO ICTRP search portal (http://www.who.int/trialsearch/).

Data collection and analysis

Selection of studies

Six review authors (WT, ZX, ZJ, XLX, QY, LG) performed the searches and retrieved articles. The same review authors selected the trials to be included in the study and no disagreements were recorded. We retrieved the selected trials which claimed to be randomised. We then confirmed that they were correctly randomised by telephoning the original trial authors.

Data extraction and management

Two review authors (WT, LG) independently extracted data using a piloted data extraction form. We extracted data on study characteristics including methods, participants, interventions and outcomes. There were no disagreements. The formulation contents of included studies and herb names in three languages are described in Table 1 and Table 2.

1. Contents of the formulations used in the included studies.

Study ID	Contents	Method of administration
Chang 2002	Did not provide any information about the contents of interventions including Shanhanjiere Koufuye and Biaoshi Ganmao Chongji	Each ml solution contained 2 g of raw drug material. Each ampoule contained 4 ml. One ampoule for children younger than 4 years of age was administered by the rectal route; and 2 ampoules were administered for children older than 4 years of age, 3 times a day.
Chang 2005	Jinlianhua, Daqinye, Shenshigao, Zhimu, Shendi, Xuanshen, Kuxingren	Oral administration
Chang 2007	Gegen Qingre granule: Chaihu, Gegen, Huangqin, Mahuang, Shigao, Xingren, Gancao	Oral water dilution
Chen 2004	Gegen, Huangqin, Huanglian, Zhigancao	Oral administration
Li 1998c	Qinwinkeli: the author mentioned that Qinwinkeli consisted of 5 herbs, but just listed 2 in the paper: Shigao, Sangye	Oral water dilution
Li 1999b	Qinkailing injection: Niuhuang, Shuiniujiao, Zhenzhumu, Huangqin, Zhizi, Jinyinghua, Banlangen 10 ml contains 50 mg baicalin	Intravenous injection
Liu 2002	Kangbingdupian: Banlangen, Lianqiao, Shigao, Shendi, Guanghuoxiang, Yujin, Shichangpu	Oral administration
Ma 2000b	Shuanhua aerosol: Yejuhua, Jinyinghua, Yuxingchao, Chaihu, Boheyou
Mei 2003	Yujin injection: water extraction of Yuxingcao, Jinyinghua	Intravenous injection
Pan 2000	Xiaoer Riganling Koufuye: Gegen, Taurine (Taurine is not a herb)	Oral administration
Song 2004a	TCM cream Xiaoer Tuiresan: Mahuan 100 g, Jinyinhua 200 g, Shandougen 100 g, Xixin 10 g, Bohe 100 g, Bingpian 80 g, Gancao 60 g, grind them to be very fine powder and mix them. Take 3 to 10 g preparation with the correct amount of vinegar to make a cream and smear on a plastic membrane.	Apply to the skin
Wang 1998	Jianerqinjieye: Jinyinhua, Hangjuhua, Lianqiao, Kuxinren, Shanzha, Chenpi	Oral administration
Wang 2004	Sufeng Ganmao Koufuye: Zisuye, Qianghuo, Jinjie, Guanghexiang, Fangfeng, Qianhu, Fuping, Fulinpi	Oral administration
Wang 2008a	Yiqing Shuangjie capsule and tablet: Huangqin, Chaihu, Rengong Niuhuang	Oral administration
Yang 2000	Huanghu Bag Tea: Huangqin, Lianqiao, Huzhang, Shanzhima, Jinyinhua, Qinhao, Chaihu	Oral administration
Yu 1997	Chaiqin Qingre enema lavage solution: Chaihu, Huangqin, Xixin	Oral administration
Zhang 2001	Rebining: no other information was provided
Zhang 2008	Qingyin injection: Huangqin, Yinhua	Intravenous injection

2. Chinese herbs in different languages.

Pingying name	Latin name	English name
Huangqin	Radix Scutellariae	Baical Skullcap root
Lianqiao	Fructus Forsythiae	Weeping Forsythia capsule
Huzhang	Rhizoma Polygoni Cuspidati	Giant Knotweed rhizome
Shanzhima	Radix Helicteris	Narrowleaf Screwtree root
Jinyinhua	Flos Lonicerae	Honeysuckle flower
Qinhao	Herba Artemisiae	Sweet Wormwood herb
Chaihu	Radix Bupleuri	Chinese Thorowax root /Red Thorowax root
Xixin	Herba Asari	Manchurian Wildginger
Gegen	Radix Puerariae	Kudzuvine root
Huanglian	Rhizoma Coptidis	Colden thread
Zhigancao	Radix Glycyrrhizae	Liquorice root
Hangjuhua	Flos Chrysanthemi	Chrysanthemun flower
Kuxinren	Semen Armeniacae Amarum	Apricot kernel
Shanzha	Fructus Crataegi	Hawthorn fruit
Chenpi	Pericarpium Citri Reticulatae	Dried Tangerine peel
Niuhuang	Calculus Bovis	Bezoar
Shuiniujiao	Cornu Bubali	Buffalo horn
Zhenzhumu	Concha Margaritifera Usta	Nacre
Zhizi	Fructus Gardeniae	Cape Jasmine fruit
Banlangen	Radix Isatidis	Isatis root
Shigao	Gypsum Fibrosum	Gypsum
Sangye	Folium Mori	Mulberry leaf
Yejuhua	Flos Chrysanthemi Indici	Wild Chrysanthemum
Yuxingcao	Herba Houttuyniae	Heartleaf Houttuynia Herb
Boheyou	Herba Menthae oil	Peppermint oil
Sisuye	Folium Perillae	Perilla leaf
Qianghuo	Rhizoma Notopterygii	Incised Notopterygium rhizome/Forbes Notopterygium rhizome
Jinjie	Herba Schizonepetae	Fineleaf Schizonepeta herb
Guanghexiang	Herba Pogostemonis	Cablin Potchouli herb
Fangfeng	Radix Saposhnikoviae	Divaricate Saposhnikovia root
Qianhu	Radix Peucedani	Whiteflower Hogfennel root/Common Hongfennel root
Fuping	Herba Spirodelae	Common Ducksmeat herb
Fulinpi	Poria skin	Indian Buead skin
Jinlianhua	Flos Trollii	Chinese Globeflower flower
Daqingye	Folium Isatidis	Indigowoad leaf
Shenshigao	Gypsum Fibrosum	Gypsum
Zhimu	Rhizoma Anemarrhenae	Common Anemarrhena rhizome
Shendi	Radix Rehmanniae	Rehmannia root
Xuanshen	Radix Scrophulariae	Figwort root
Kuxingren	Semen Armeniacae Amarum	Bitter Apricot Seed
Yujin	Radix Curcumae	Turmeric root‐tuber
Mahuang	Herba Ephedrae	Ephedra herb
Shandougen	Radix Sophorae Tonkinensis	Vietnamese Sophora root
Bohe	Herba Menthae	Peppermint
Bingpian	Borneolum	Borneol
Gancao	Radix Glycyrrhizae	Liquoric root
Shichangpu	Rhizoma Acori Tatarinowii	Grassleaf Sweelflag rhizome
Chuanxinlian	Herba Andrographis	Common Andrographis herb

We performed an intention‐to‐treat (ITT) analysis on three trials (Chang 2005; Chang 2007; Wang 2008a). We performed per‐protocol analyses on the other studies. We reported the number lost to follow up in the notes column of the 'Characteristics of included studies' table.

Assessment of risk of bias in included studies

We assessed the risk of bias of each trial in terms of generation of allocation sequence, allocation concealment, blinding, uncompleted data and selective reporting; and classified them as 'low risk', 'moderate risk', or 'high risk' according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions 5.0.0 (Higgins 2008) and as described in Wu 2007a. There was no disagreement in this process.

Sequence generation

An adequate approach for generating allocation sequence with a low risk of selection bias should be by using a random numbers table or computer software, or other simple randomisation methods, for example, coin tossing or card shuffling. We considered a trial which only mentions 'random' but does not include a description of the approach used as a moderate risk of selection bias.

Allocation sequence concealment

Low risk of selection bias: adequate measures to conceal allocation sequence is defined as the person who generates an allocation sequence not recruiting the participants, for example, by central randomisation. Examples of concealing allocation sequences are using sealed opaque envelopes or storing allocation sequences in a locked computer.

Moderate risk of selection bias: where concealment of the allocation sequence is mentioned but the approach used is not reported.

High risk of selection bias: allocation concealment is reported inadequately, or is not performed at all.

Level of blinding

Masking of both the participants and results assessor was considered as a low risk of performance or/and detection bias.

Single blinding of the results assessor was considered as a moderate risk of performance or/and detection bias. If single blinding was performed on the participants but not the results assessor, it was considered as a high risk of detection bias.

Non‐blinding for detection of outcomes includes quality of life (QoL); adverse events were considered as a high risk of detection bias. Blinding was not considered necessary for reporting mortality.

Incomplete outcome data: assessment for potential bias of exclusions and attrition

Low risk of bias: trials where few exclusions and attrition are noted and an intention‐to‐treat (ITT) analysis is possible.

Moderate risk of bias: trials which report the rate of exclusions or/and attrition to be about 10%, whatever ITT analysis is used.

High risk of bias: the rate of exclusion or/and attrition is higher than 15%, or there are wide differences in exclusions between groups, whatever ITT analysis is used.

Measures of treatment effect

We analysed the data using Review Manager 5 (RevMan 2008). We compared outcome measures for binary data using risk ratios. For continuous data, we used the mean difference. We conducted a pooled analysis for two trials only (Chang 2002; Yu 2005).

Assessment of heterogeneity

We assessed heterogeneity by using the Chi² test with a 10% level of statistical significance and by using the I² statistic to estimate the total variation across studies that was due to heterogeneity rather than chance. Less than 25% was considered as low level heterogeneity; 25% to 50% was considered as a moderate level; and higher than 50% as a high level of heterogeneity (Higgins 2002).

Assessment of reporting biases

No ‐ low risk of reporting bias: all outcomes are reported in detail. 
 Probably yes ‐ moderate risk of reporting bias: at least one of the outcomes are mentioned, but not in detail. 
 Yes ‐ high risk of reporting bias: at least one of the outcomes are not reported.

Data synthesis

We used the random‐effects model for a pooled analysis of the two studies (Chang 2002; Yu 2005) as most of the studies had a high level of heterogeneity. We did not perform a pooled analysis for the other trials due to unknown formulations used in these trials. We listed non‐randomised controlled studies and the reasons of exclusion in the 'Characteristics of excluded studies' table, but did not discuss them further.

Results

Description of studies

Results of the search

A total of 430 trials that claimed to be randomised were retrieved. We successfully contacted 365 trial authors by telephone. Of these trials, 302 were excluded, either because the trial authors misunderstood true random allocation or the trial reports were multiple versions of same study (see the 'Characteristics of excluded studies' table), of those, 67 were additional studies later excluded in this updated version of review.

One hundred and nine are listed in the 'Studies awaiting classification' section. One of these studies, for example, assessed an intervention containing 'Yuxincao', a drug which the State Food and Drug Administration (SFDA) stopped production of, due to unclear adverse events. Other trials are allocated to this section as we could not locate the original trial authors to identify the randomisation method.

Seventeen studies were identified as true RCTs and fulfilled our inclusion criteria (Chang 2002; Chang 2005; Chang 2007; Chen 2004; Li 1998; Li 1999a; Liu 2002; Ma 2000; Pan 2000; Song 2004a; Wang 1998; Wang 2004; Wang 2008a; Yang 2000; Yu 1997; Yu 2005; Zhang 2008), of those, three (Chang 2007; Wang 2008a; Zhang 2008) were additional trials later included in this updated version of review.

Included studies

All 17 included trials used a parallel group design. Four trials (Chang 2007; Li 1999a; Wang 2008a; Zhang 2008) were multi‐centre trials.

A total of 3212 participants were included in the 17 trials, with numbers of participants in each trial varying from 58 to 463. Only three trials (Chang 2005; Chang 2007; Wang 2008a) mentioned that the sample size was calculated according to the SFDA's regulation about sample size of non‐inferiority test studies (that a total number of 200 participants be included); extra participants were also included in these trials to avoid possible attrition bias.

Nine trials included children aged from six months to 14 years (Chen 2004; Li 1998; Liu 2002; Ma 2000; Pan 2000; Song 2004a; Wang 1998; Yang 2000; Yu 1997). Eight trials included adults aged from 18 to 65 or 72 years old (Chang 2002; Chang 2005; Chang 2007; Li 1999a; Wang 2004; Wang 2008a; Yu 2005; Zhang 2008).

Eleven trials included participants according to TCM signs. Nine trials (Chang 2005; Chang 2007; Chen 2004; Li 1998; Li 1999a; Ma 2000; Wang 2008a; Yang 2000; Zhang 2008) included patients with "fever cold". One trial (Yu 1997) included both "fever cold" and "chills cold" patients. Three trials (Chang 2002; Wang 2004; Yu 2005) included "chills cold". Two trials (Pan 2000; Wang 1998) did not sort the patients by TCM signs.

Two trials (Chang 2002; Yu 2005) compared the Chinese herbs Sanhan Jiere Koufuye and (Fenghan) Biaoshi Ganmao Chongji. Other trials used different interventions and comparators. These are listed below:

• Yu 1997 compared Caichen Qinre Weixin Guanchangji with virazole and acetaminophen.

• Li 1998 compared Qinwen Keli granule with Kangbingdu Koufuye.

• Wang 1998 compared Jianer Qinjie Ye with Qinre Jiedu Koufuye.

• Li 1999a compared Qinkailing injection with Lincomycine.

• Ma 2000 compared Shuanghua Penhuji with Shuanghuanglian Qiwuji.

• Pan 2000 compared Xiaoer Reganning with Vitamin C Yinqiao Chongji.

• Yang 2000 compared Huanghu Jiere Daipaoji with Shiqi Ganmao Daipaoji.

• Liu 2002 compared Kangbingdupian with Banlangen Chongji.

• Chen 2004 compared Gegen Cenlianwei Wan with Yinqiao Jiedupian.

• Song 2004a compared self‐prepared TCM cream with penicillin or lincomycin.

• Wang 2004 compared Sufeng Ganmao Koufuye with Ganmao Qinre Koufuye.

• Chang 2005 compared Jinlian Qinre capsules with Jinlian Qinre granules; that is the same ingredients in two different forms. The principle of selecting the control drug was that its "effect was commonly recognised". A double‐dummy placebo was used in both arms.

• Chang 2007 compared Chaige Qingre granule with Fufang Shuanghua granule.

• Wang 2008a used a double‐dummy placebo in both arms, and compared Yiqing Shuangjie granule and Chaihuang tablet placebo with Chaihuang tablet, and compared Yiqing Shuangjie tablet and Caihuang tablet placebo with Chaihuang tablet.

• Zhang 2008 compared Qingyin injection with Qinkailing injection

Recovery (expressed as a dichotomous event) was used as a primary outcome in all trials, except for Pan 2000 and Zhang 2008. Inefficacy was reported in 15 trials. Fever clearance time was reported in six trials (Chang 2002; Chang 2005; Li 1998; Wang 1998; Wang 2008a; Yu 1997). The time point at which the temperature started to abate was reported in four trials (Chang 2005; Li 1998; Wang 1998; Wang 2008a). Six trials (Chang 2002; Chang 2005; Chen 2004; Li 1999a; Wang 2008a; Yu 1997) compared the prevalence of viral respiratory tract infection by a throat swab culture. Five trials reported that liver and kidney function tests were carried out to look for side effects or adverse events (Chang 2002; Chang 2005; Chang 2007; Wang 2008a; Zhang 2008).

Eight trials (Chang 2002; Chang 2005; Chang 2007; Chen 2004; Song 2004a; Wang 2004; Wang 2008a; Yu 2005) evaluated changes of TCM signs, which included "e feng han" (fear of wind and cold); "fa re" (fever); "bi sai liu ti" (snuffles and runny nose); examination of the colour and surface of the tongue; and "mai xiang" (examining the pulse).

Risk of bias in included studies

Randomisation

Three trials (Chang 2002; Song 2004a; Yang 2000) mentioned that a random numbers table was used to generate the allocation sequence. Three trials (Chang 2005; Chang 2007; Wang 2008a) mentioned that SAS software was used to generate the sequences. The other 11 trials mentioned "random allocation", but no description about which methods were used. After telephoning the trial authors, we learned that a random numbers table was used in seven trials (Chen 2004; Li 1998; Liu 2002; Ma 2000; Song 2004a; Yu 1997; Yu 2005). Five trials used computer software (Li 1999a; Pan 2000; Wang 2004; Zhang 2001; Zhang 2008) and one trial (Wang 1998) used the method of "mo jiu" (drawing straws).

Allocation

Only three trials (Chang 2005; Chang 2007; Wang 2008a) mentioned that the allocation sequence was concealed by using opaque, sealed envelopes. The other trials did not provide any information about allocation concealment. The allocation sequence of the three trials Chang 2002, Wang 2004 and Yu 2005 was confirmed to be adequate via communication with the trial authors.

Blinding

Single blinding was used in two trials (Chen 2004; Pan 2000) and double blinding was used in six trials (Chang 2005; Chang 2007; Wang 2004; Wang 2008a; Yang 2000; Zhang 2008). The remaining nine trials did not use blinding.

Chang 2005 and Wang 2008a used a double‐dummy placebo to guarantee successful blinding but there was a high risk of detection bias in these trials. Only one trial (Chang 2007) described the methods of double blinding. Other trials did not mention how they used blinding.

Incomplete outcome data

Assessment for potential bias exclusions and attrition

Six trials (Chang 2002; Chang 2005; Chang 2007; Wang 2004; Wang 2008a; Zhang 2008) reported a loss of participants for the above listed reasons. Three trials (Chang 2005; Chang 2007; Wang 2008a) used both ITT and per‐protocol analysis, and two trials (Chang 2002; Wang 2004) used per‐protocol analysis only.

Selective reporting

Assessment for reporting bias

Selective reporting was not identified in the trials.

Effects of interventions

We performed a pooling analysis on two trials only (Chang 2002; Yu 2005) due to heterogeneity in the interventions and controls.

1. Recovery

Trials showing statistically significant differences between the intervention and comparison

Six trials reported that the intervention group had a statistically significant better recovery than the control group. Of these, three studied children (Li 1998; Ma 2000; Song 2004a) and the other three studied adults (Li 1999a; Wang 2004; Wang 2008a) with the common cold. The results are shown below:

1. Qinwen Keli granule was more effective than Kangbingdu Koufuye (risk ratio (RR) 2.19, 95% confidence interval (CI) 1.61 to 2.96) (Li 1998);

2. Shuanghua Penhuji was more effective than Shuanghuanglian Qiwuji (RR 1.48, 95% CI 1.11 to 1.97) (Ma 2000);

3. TCM cream was more effective than penicillin (RR 2.10, 95% CI 1.20 to 3.67) (Song 2004a);

4. Sufeng Ganmao Koufuye was more effective than Ganmao Qinre Koufuye (RR 1.43, 95% CI 1.02 to 1.99) (Wang 2004);

5. Qinkailing injection was more effective than lincomycin in three doses, respectively (120 ml/day RR 1.41, 95% CI 1.07 to 1.86; 160 ml/day RR 1.41, 95% CI 1.08 to 1.86; and 200 ml RR 1.52, 95% CI 1.15 to 2.00) (Li 1999a);

6. YiQing ShuanJie capsule and YiQing ShuanJie tablet was more effective than Chaihuang tablet respectively (YiQing ShuanJie capsule RR 1.59, 95% CI 1.08 to 2.33, and YiQing ShuanJie tablet RR 1.67, 95% CI 1.14 to 2.43) (Wang 2008a).

Trials showing no statistically significant differences between the intervention and comparison

Another eight trials showed no statistically significant differences in duration of symptoms between the intervention and control groups. Of these, four studied adults (Chang 2002; Chang 2005; Chang 2007; Yu 2005) and the others studied children (Chen 2004; Wang 1998; Yang 2000; Yu 1997).

1. Jinlian Qinre capsule versus Jinlian Qinre granule (RR 0.97, 95% CI 0.58 to 1.62) (Chang 2005);

2. Sanhan Jiere Koufuye versus (Fenghan) Biaoshi Ganmao Chongji (combined RR 1.51, 95% CI 0.79 to 2.90) (Chang 2002; Yu 2005). A sensitivity analysis was performed by deselecting the study by Yu 2005 which had been conducted in same hospital as the preparation provider showed that it had a similar result (RR 1.20, 95% CI 0.85 to 1.69);

3. Gegen Cenlianwei Wan versus Yinqiao Jiedupian (RR 1.17, 95% CI 0.80 to 1.73) (Chen 2004);

4. Jianer Qinjieye versus Qinre Jiedu Koufuye (RR 1.45, 95% CI 0.99 to 2.13) (Wang 1998);

5. Huanghu Jiere Daipaoji versus Shiqi Ganmao Daipaoji (RR 3.62, 95% CI 0.88 to 14.91) (Yang 2000);

6. Caichen Qinre Weixin Guanchangji with virazole and acetaminophen (RR 1.40, 95% CI 0.71 to 2.74) (Yu 1997).

7. A phase II and phase III trial by the same study team compared Chaige Qingre granule versus Fufang Shuanghua capsule, respectively. The combined results of these two studies showed there was no statistically significant difference between the two drugs (RR 1.05, 95% CI 0.75 to 1.48) (Chang 2007).

2. Improvement

The Pan 2000 study showed a statistically significant improvement in the severity of symptoms when using the intervention Xiaoer Reganning, compared to vitamin C (Yinqiao Chongji), for children with the common cold (RR 1.69, 95% CI 1.22 to 2.35). In this trial, the definition of 'improvement' included both shortening of the duration of symptoms and lessening of the severity of symptoms. The other 14 trials and two combined trials showed no differences between the two groups on lessening of severity of symptoms.

Seven trials showed that the number of inefficacies in the intervention group was statistically significantly less than the control group. Of these, one trial (Wang 2004) included adults and the other trials included children:

1. Qinwen Keli granule was more effective than Kangbingdu Koufuye (RR 0.41, 95% CI 0.19 to 0.90) (Li 1998);

2. Kangbingdupian was more effective than Banlangen Chongji (RR 0.20, 95% CI 0.05 to 0.87) (Liu 2002);

3. Shuanghua Penhuji was more effective than Shuanghuanglian Qiwuji (RR 0.16, 95% CI 0.03 to 0.87) (Ma 2000);

4. Jianer Qinjieye was more effective than Qinre Jiedu Koufuye (RR 0.12, 95% CI 0.02 to 0.91) (Wang 1998);

5. Sufeng Ganmao Koufuye was more effective than Ganmao Qinre Koufuye (RR 0.16, 95% CI 0.07 to 0.38) (Wang 2004);

6. Huanghu Jiere Daipaoji was more effective than Shiqi Ganmao Daipaoji (RR 0.10, 95% CI 0.01 to 0.85) (Yang 2000).

7. The Yiqing Shuanjie capsule and Yiqing Shuanjie tablet have a similar effect to Chaihuang tablet (RR 0.94, 95% CI 0.71 to 1.25, and RR 0.91, 95% CI 0.68 to 1.21, respectively) (Wang 2008a).

3. Partial improvement

Five trials showed that partial improvement in the intervention group was statistically higher than the control group. Of these, one trial (Wang 2004) included adults and the remaining four trials included children with the common cold.

1. Qinwen Keli granule was more effective than Kangbingdu Koufuye (RR 1.05, 95% CI 1.00 to 1.11) (Li 1998);

2. Xiaoer Reganning was more effective than vitamin C Yinqiao Chongji (RR 1.24, 95% CI 1.02 to 1.50) (Pan 2000);

3. Jianer Qinjieye was more effective than Qinre Jiedu Koufuye (RR 1.32, 95% CI 1.05 to 1.65) (Wang 1998);

4. Sufeng Ganmao Koufuye was more effective than Ganmao Qinre Koufuye (RR 1.37, 95% CI 1.17 to 1.60) (Wang 2004).

Seven trials and a combined analysis of two trials and showed no statistically significant differences between the two groups. Of these, three trials included adults (Chang 2002; Chang 2005; Yu 2005) and the other five trials included children with the common cold.

1. Sanhan Jiere Koufuye versus (Fenghan) Biaoshi Ganmao Chongji (combined RR 1.04 95% CI 0.92 to 1.16) (Chang 2002; Yu 2005). A sensitivity analysis was performed by deselecting the trial by Yu 2005 which was conducted in the same hospital as the preparation provider, and had a same result (RR 1.01, 95% CI 0.94 to 1.09).

2. Jinlian Qinre capsules had the same efficacy as Jinlian Qinre granules (RR 1.00, 95% CI 0.95 to 1.06) (Chang 2005);

3. Gegen Cenlianwei Wan had the same efficacy as Yinqiao Jiedupian (RR 1.17, 95% CI 0.96 to 1.43) (Chen 2004);

4. Shuanghua Penhuji had the same efficacy as Shuanghuanglian Qiwuji (RR 1.05, 95% CI 0.99 to 1.12) (Ma 2000);

5. Huanghu Jiere Daipaoji had the same efficacy as Shiqi Ganmao Daipaoji (RR 1.15, 95% CI 0.98 to 1.35) (Yang 2000);

6. Caichen Qinre Weixin Guanchangji had the same efficacy as virazole and acetaminophen (RR 1.13, 95% CI 0.91 to 1.39) (Yu 1997).

4. No improvement

Nine trials showed no statistically significant differences in outcomes between the intervention and control groups. Of these, three trials (Chang 2007; Chang 2005; Li 1999a) included adults and the other trials included children.

1. Sanhan Jiere Koufuye had the same efficacy as (Fenghan) Biaoshi Ganmao Chongji (combined RR 0.49, 95% CI 0.14 to 1.73) (Chang 2002; Yu 2005). A sensitivity analysis was performed by deselecting the Yu 2005 trial, which had been conducted in the same hospital as the preparation provider and showed a similar result (RR 0.67, 95% CI 0.06 to 7.09).

2. Chaige Qingre granule had the same efficacy as Fufang Shuanghua capsule in the phase II (RR 2.00, 95% CI 0.19 to 20.86) (Chang 2007);

3. Chaige Qingre granule had the same efficacy as Fufang Shuanghua capsule in the phase III (RR 1.07, 95% CI 0.23 to 4.97) (Chang 2007);

4. Jinlian Qinre capsule had the same efficacy as Jinlian Qinre granule (RR 0.69, 95% CI 0.23 to 2.11) (Chang 2005);

5. Gegen Cenlianwei Wan had the same efficacy as Yinqiao Jiedupian (RR 0.35, 95% CI 0.01 to 8.52) (Chen 2004);

6. Xiaoer Reganning had the same efficacy as vitamin C Yinqiao Chongji (RR 0.50, 95% CI 0.23 to 1.08) (Pan 2000);

7. TCM cream Xiaoer Tuiresan had the same efficacy as penicillin or lincomycin (RR 0.25, 95% CI 0.03 to 2.11) (Song 2004a);

8. Caichen Qinre Weixin Guanchangji had the same efficacy as virazole and acetaminophen (RR 0.52, 95% CI 0.10 to 2.84) (Yu 1997).

9. Qinkailing injection had the same efficacy as lincomycin in three doses, respectively (120 ml/day RR 0.84, 95% CI 0.28 to 2.52; 160 ml/day RR 0.82, 95% CI 0.27 to 2.46; and 200 ml RR 1.35, 95% CI 0.49 to 3.73) (Li 1999a).

5. Duration of fever

Five trials reported no difference in the duration of fever between the intervention and control groups. Two of these trials reported no difference in the number of participants whose temperatures were normalised within 24 hours (Chang 2002), 48 hours and 72 hours (Yu 1997): Sanhan Jiere Koufuye versus (Fenghan) Biaoshi Ganmao Chongji (RR 1.02 95% CI 0.85 to 1.22) (Chang 2002); and Caichen Qinre Weixin Guanchangji versus virazole and acetaminophen (RR 1.46, 95% CI 0.89 to 2.40, and RR 0.33, 95% CI 0.11 to 0.99, respectively) (Yu 1997).

Likewise, another three trials (Chang 2002; Chang 2005; Wang 2008a) showed no difference in duration of fever between the two groups (WMD ‐0.29 hours, 95% CI ‐2.26 to 1.68, WMD ‐3.91 hours, 95% CI ‐8.24 to 0.42, WMD 4.20 hours, 95% CI ‐1.41 to 9.81 and WMD 3.62 hours, 95% CI ‐2.74 to 9.98, respectively).

Three trials (Chang 2005; Li 1998; Wang 1998) reported a statistically significantly shorter duration of fever in the treatment group compared to the control group 2.02, 6.90 and 5.70 hours, respectively (WMD ‐2.02, 95% CI ‐3.86 to ‐0.18; WMD ‐6.90, 95% CI ‐9.94 to ‐3.86, and WMD ‐5.70, 95% CI ‐10.09 to ‐1.31, respectively). One study (Li 1998) showed that in the treatment group the average duration of fever was longer than control group by 11.60 hours (WMD ‐11.60, 95% CI ‐15.65 to ‐7.55).

Another trial (Wang 2008a) showed no statistically significant differences in the time to resolution of fever in the treatment group A and B as compared to the control group (WMD ‐2.06 hours, 95% CI ‐5.02 to 0.90, and WMD ‐1.44 hours, 95% CI ‐4.70 to 1.82).

6. Adverse events

None of the trials reported any adverse events, according to our definitions.

7. Additional outcomes

Seven trials (Chang 2002; Chang 2005; Chang 2007; Chen 2004; Wang 2004; Wang 2008a;Yu 2005) reported effects on TCM signs. We only analysed data in two studies (Chang 2005; Chen 2004). There were no statistically significant differences between the two groups in these trials.

Discussion

Summary of main results

Studies of Chinese herbal medicines for the common cold lack sufficient power to provide reliable estimates of their efficacy, due to poor study design and methodological quality.

Although Chinese herbal medicines as a treatment for the common cold and the methods of manufacturing these medicines are widely accepted in China, most of the constituents of the pharmacologically prepared drugs used in trials cannot be specified. This is in marked contrast to the pharmacological agents used in Western medicine, for which the chemical constituents, their quantities and the percentage of any impurities or contaminants are precisely known. In addition, the variation between different production batches of Western medicines is kept within specified limits. In contrast, variation between formulations and batches of pharmacological agents are inevitable in traditional Chinese medicine (TCM), although the Chinese Government specifies the acceptable limits of variation. This variation is a factor that may contribute to any heterogeneity between different study results.

A large number of the trials initially identified claimed to be randomised controlled trials (RCTs). However, after contacting the trial authors to request information regarding the method of randomisation used, we found that more than 95% of the authors misunderstood the concept of randomisation. In addition to this, some of the studies were conducted several years ago, and the trial authors may have forgotten the details of the methodology they employed. This could lead to a memory bias and undermine the veracity of information.

Some studies (Chang 2002; Li 1998; Li 1999a; Ma 2000; Wang 2004; Yang 2000; Yu 1997) used unequal arms in their design. Of these studies, Yu 1997 used a proportion of 3:1, and only 15 patients were included in the control group (43:15). However, consideration of the sample sizes was not reported in these trials, which makes it difficult to detect the differences between the two groups accurately. This may lead to a low test power.

Finally, we considered it pertinent to attempt to compare selected TCM signs in different groups of participants. TCM signs are difficult to quantify because they use subjective outcomes. For example, 'wu han' means that the participant feels cold whilst also having a fever, and this can be divided into low, medium and high categories, depending on the participants' subjective view. 'Mai xiang' measures the pulse; in TCM it is a complex and difficult technique to judge this accurately and often dependent upon on the physician's experience. TCM researchers and physicians should decide upon an accurate and consistent method of measuring TCM signs.

Quality of the evidence

None of the trials included in this review used a placebo as a control: instead "positive effect drugs" were selected. Two studies (Chang 2005; Chang 2007) mentioned that the rule of selecting the control drug was that "the effect was generally acknowledged". This may result in false positive findings, as a number of interventions are considered effective for the common cold, particularly if trial conductors know that a "positive" drug was used in the trial and the purpose of the study was to demonstrate the same effect as the control (so called "equal effect test"). For example, Chang 2005 compared two different forms of the same ingredient. In this case, "double blinding" would not be a valid term. This may result in false positive findings: if the trialist knows that a "positive" drug was used and the study was an "equal effect test" study, there is a potential risk that the outcome detectors will give same results for the two groups. For example, the purpose of Chang 2005 was to compare two different forms of the same drug; one was in a granule form and the other was in a capsule form and the trialists were aware of this. Therefore, there was a possibility that the results were not scrutinised carefully ‐ particularly the subjective outcomes. In this case "double blinding" does not have any value.

We found that three trials claimed to have used 'double blinding' (Chang 2005; Chang 2007; Yang 2000) and one used 'single blinding' (Chen 2004). These studies found a similar recovery rate as the "positive" control. Two of the 'double blinding' studies (Wang 2004; Wang 2008a) found the recovery rate in the intervention group to be higher than the control group by almost 50% (Wang 2004 RR 1.43; Wang 2008a RR 1.59 and RR 1.67). However, Wang 2004 lacked a description of how to verify the success of the blinding. Another trial (Pan 2000) found the marked improvement rate in the intervention group to be higher than the control group (RR 1.69). For a disease like the common cold, which can go into spontaneous remission within one week, it is very difficult to find that the effect of a new drug is better than the "positive effect" of the control drugs. We have to point out that the possible reason that the relative risk is so high is that a high risk of selection bias, detection bias or both may have existed in the studies where the effects were similar or higher than "positive effect" controls.

Many trials incorrectly used drugs whose effects have not been demonstrated as a control. Thus it is difficult to determine the efficacy of the intervention by comparison. Where the intervention is equal in efficacy to the control, no conclusion can be made. For example, the average rate of recovery from the common cold was the same for those participants taking Jinlian Qinre capsules (intervention) and Jinlian Qinre granules (control) (Chang 2005). Since there is no evidence assessing the efficacy of Jinlian Qinre granules, we therefore cannot determine the efficacy of Jinlian Qinre capsules.

Potential biases in the review process

We found the formulations of interventions in five studies (Ma 2000; Pan 2000; Yang 2000; Yu 1997; Yu 2005) were prepared by either the trial authors or colleagues in their hospital. Furthermore, in these five studies, the trial authors designed the interventions used and trial methods, making them open to bias towards the intervention. For example, the same intervention and control drugs were assessed in two studies (Chang 2002; Yu 2005). The former demonstrated a similar efficacy of the two drugs, however the latter demonstrated that Shanhan Jiere Koufuye was more effective than Biaoshi Ganmao Chongji. A possible explanation for this discrepancy is that the formulation of Shanhan Jiere Koufuye was designed by the trial author's hospital and the reported number of full recovery of symptoms may have been underestimated in Yu 2005. That is, Yu 2005 reported six recoveries from 30 cases, whilst Chang 2002 reported 17 recoveries from 30 participants. Selection bias, detection bias or both in the Yu 2005 trial could be an acceptable explanation for this discrepancy.

It is important that high quality trials should use a valid control group and a small number of preparations or interventions with known compositions, subgrouped by TCM criteria and standardised by Chinese or Western specialists in this field. Study designs and reporting should be improved in future research.

Authors' conclusions

Implications for practice.

We could not find a well‐designed trial to provide strong evidence to support the use of any Chinese traditional herbal medicines for the treatment of the common cold.

Implications for research.

Further randomised clinical trials of herbal medicine for treating the common cold are required. It is essential that such trials have adequate methods of randomisation and allocation sequencing, and use a placebo or no treatment as a control. If a herbal medicine is a control, only those medicines which have a demonstrated effect on the common cold should be used. Blinding of participants, trial authors and outcome detectors is necessary. The design for calculating the sample size should be reported. The information on trial conduction should be reported in detail according to CONSORT (Moher 2001) and CONSORT for traditional Chinese medicine (TCM) (Wu 2007c).

What's new

Date	Event	Description
9 September 2010	Amended	Contact details updated.

History

Protocol first published: Issue 2, 2004
 Review first published: Issue 1, 2007

Date	Event	Description
16 June 2010	Amended	Contact details updated.
13 May 2010	Amended	Contact details updated.
21 January 2010	Amended	Contact details updated.
29 May 2008	New search has been performed	Searches conducted. Some studies were identified as authentic randomised controlled trials and have been included in this updated review. The conclusions remain unchanged.
25 June 2008	Amended	Converted to new review format.
1 August 2006	New search has been performed	Searches conducted.

Notes

The following studies are currently 'awaiting assessment'. In all cases we are attempting to identify the randomisation method they were used:

Cai 2001; Chen 1998; Chen 2000a; Chen 2000b; Chen 2001a; Chen 2002; Ding 2004; Ding 2007; Dong 2004; Fang 2008; Feng 1997; Feng 2008; Gu 2004; Gu 2005a; Guo 1996; Guo 2000b; Han 2003; Han 2003b; Hao 2004; He 2001; Hou 1998; Hu 1997; Hu 2007a; Huang 1997; Huang 2000; Huang 2002; Jiang 1996; Jiang 2003b; Jiang 2008; Li 2000b; Li 2001; Li 2002a; Li 2002b; Li 2002d; Li 2002e; Li 2004b; Li 2004c; Li 2004d; Liang 2000; Lin 1999b; Lin 2001; Ling 1998; Liu 2001a; Liu 2007; Liu 2008b; Luo 2003; Luo 2007; Lv 2001; Ma 2000a; Ma 2000c; Mei 2003; Meng 2000; Meng 2003a; Meng 2003b; Miao 2000; Miao 2002; Nie 2000; Niu 2003; Ren 2003; Rong 1999; Sheng 2001; Shi 1998a; Su 1994; Sun 1999a; Tao 1996; Tao 2001; Wang 1995c; Wang 2008c; Wei 2008; Wu 2002a; Wu 2002b; Wu 2003c; Xu 1999a; Xu 1999b; Yan 2000; Yang 1999a; Yu 2003; Yu 2004a; Yu 2007b; Yuan 1999; Zeng 2005; Zhang 1997; Zhang 1999b; Zhang 2000b; Zhang 2000c; Zhang 2002a; Zhang 2002b; Zhang 2002e; Zhang 2003d; Zhang 2004b; Zhang 2004c; Zhang 2004d; Zhang 2004e; Zhao 2001b; Zheng 1996; Zheng 1998; Zheng 2001; Zhong 2002; Zhou 1999a; Zhou 1999b; Zhou 2003; Zhou 2004a; Zhou 2004c; Zhu 2000a; Zhu 2000b; Zhu 2002a; Zhu 2004b; Zou 1997b; Zuo 2008.

Appendices

Appendix 1. CENTRAL search strategy

CENTRAL (WIS Online)

#1 MeSH descriptor Common Cold explode all trees 
 #2 "common cold" 
 #3 MeSH descriptor Rhinovirus explode all trees 
 #4 rhinovirus* 
 #5 (upper NEXT respiratory NEXT tract NEXT infection*) or URTI 
 #6 (upper NEXT respiratory NEXT infection*) or URI 
 #7 (#1 OR #2 OR #3 OR #4 OR #5 OR #6) 
 #8 MeSH descriptor Medicine, Chinese Traditional explode all trees 
 #9 MeSH descriptor Drugs, Chinese Herbal explode all trees 
 #10 herbal NEXT medic* 
 #11 medicinal NEXT herb* 
 #12 chinese NEXT herb* 
 #13 chinese NEXT medic* 
 #14 (#8 OR #9 OR #10 OR #11 OR #12 OR #13) 
 #15 (#7 AND #14)

Data and analyses

Comparison 1. Chinese herbs versus controls.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change of symptoms	14		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.1 Recovery	9		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 Improvement	13		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.3 Partial improvement	12		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.4 No improvement	11		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.5 Recovery (Qinkailing: 120 ml/day)	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.6 Recovery (Qinkailing: 160 ml/day)	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.7 Recovery (Qinkailing: 200 ml/day)	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.8 No improvement (Qinkailing: 120 ml/day)	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.9 No improvement (Qinkailing: 160 ml/day)	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.10 No improvement (Qinkailing: 200 ml/day)	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Change of symptoms (Sanhan Jiere Houfuye)	2		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
2.1 Recovery (Sanhan Jiere Koufuye and (Fenghan) Biaoshi Ganmao Chongji)	2	180	Odds Ratio (M‐H, Fixed, 95% CI)	2.14 [1.09, 4.18]
2.2 Improvement Sanhan Jiere Koufuye and (Fenghan) Biaoshi Ganmao Chongji)	2	180	Odds Ratio (M‐H, Fixed, 95% CI)	0.68 [0.34, 1.37]
2.3 Partial improvement Sanhan Jiere Koufuye and (Fenghan) Biaoshi Ganmao Chongji)	2	180	Odds Ratio (M‐H, Fixed, 95% CI)	2.04 [0.58, 7.19]
2.4 No improvement (Sanhan Jiere Koufuye and (Fenghan) Biaoshi Ganmao Chongji)	2	180	Odds Ratio (M‐H, Fixed, 95% CI)	0.49 [0.14, 1.73]
3 Recovery	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
3.1 Chaige Qingre granule versus Fufang Shuanghua capsule	1	161	Risk Ratio (M‐H, Fixed, 95% CI)	1.05 [0.75, 1.48]
3.2 Yiqing Shuangjie capsule	1	226	Risk Ratio (M‐H, Fixed, 95% CI)	1.59 [1.08, 2.33]
3.3 Yiqing Shuangjie tablet	1	230	Risk Ratio (M‐H, Fixed, 95% CI)	1.67 [1.14, 2.43]
3.4 Yiqing Shuangjie capsule (ITT)	1	226	Risk Ratio (M‐H, Fixed, 95% CI)	1.66 [1.13, 2.42]
3.5 Yiqing Shuangjie tablet (ITT)	1	230	Risk Ratio (M‐H, Fixed, 95% CI)	1.80 [1.24, 2.60]
4 Improvement	2		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
4.1 Chaige Qingre granule versus Fufang Shuanghua capsule	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.2 Yiqing Shuangjie capsule	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.3 Yiqing Shuangjie tablet	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.4 Yiqing Shuangjie capsule (ITT)	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.5 Yiqing Shuangjie tablet (ITT)	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
5 Partial improvement	2		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
5.1 Chaige Qingre granule versus Fufang Shuanghua capsule	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.2 Yiqing Shuangjie capsule	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.3 Yiqing Shuangjie tablet	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.4 Yiqing Shuangjie capsule (ITT)	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.5 Yiqing Shuangjie tablet (ITT)	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 No improvement	2		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
6.1 Chaige Qingre granule versus Fufang Shuanghua capsule	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.2 Yiqing Shuangjie capsule	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.3 Yiqing Shuangjie tablet	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.4 Yiqing Shuangjie capsule (ITT)	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.5 Yiqing Shuangjie tablet (ITT)	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
7 Number of participants whose temperature normalised at 24, 48, 72 hours after drug administration	2		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
7.1 Within 24 hours	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
7.2 Within 48 hours	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
7.3 Within 72 hours	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
8 Time temperature started to abate	4		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
8.1 Jinlian Qinre capsules versus Jinlian Qinre granules	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
8.2 Qinwen Keli granule versus Kangbingdu Koufuye	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
8.3 Jianer Qinjie Ye versus Qinre Jiedu Koufuye	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
8.4 Yiqing Shuangjie capsule	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
8.5 Yiqing Shuangjie tablet	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
9 Average duration of fever time	4		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
9.1 Qinwen Keli granule versus Kangbingdu Koufuye	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
9.2 Jinlian Qinre capsules versus Jinlian Qinre granules	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
9.3 Sanhan Jiere Koufuye versus (Fenghan) Biaoshi Ganmao Chongji	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
9.4 Yiqing Shuangjie capsule	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
9.5 Yiqing Shuangjie tablet	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
10 TCM signs (ITT analysis)	2		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
10.1 Recovery	2		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
10.2 Improvement	2		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
10.3 Partial improvement	2		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
10.4 No improvement	2		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

1.1. Analysis.

Comparison 1 Chinese herbs versus controls, Outcome 1 Change of symptoms.

1.2. Analysis.

Comparison 1 Chinese herbs versus controls, Outcome 2 Change of symptoms (Sanhan Jiere Houfuye).

1.3. Analysis.

Comparison 1 Chinese herbs versus controls, Outcome 3 Recovery.

1.4. Analysis.

Comparison 1 Chinese herbs versus controls, Outcome 4 Improvement.

1.5. Analysis.

Comparison 1 Chinese herbs versus controls, Outcome 5 Partial improvement.

1.6. Analysis.

Comparison 1 Chinese herbs versus controls, Outcome 6 No improvement.

1.7. Analysis.

Comparison 1 Chinese herbs versus controls, Outcome 7 Number of participants whose temperature normalised at 24, 48, 72 hours after drug administration.

1.8. Analysis.

Comparison 1 Chinese herbs versus controls, Outcome 8 Time temperature started to abate.

1.9. Analysis.

Comparison 1 Chinese herbs versus controls, Outcome 9 Average duration of fever time.

1.10. Analysis.

Comparison 1 Chinese herbs versus controls, Outcome 10 TCM signs (ITT analysis).

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Chang 2002.

Methods	Parallel design. The study stated that a random numbers table was used to generate the allocation sequence. There was no blinding.
Participants	Patients aged 18 to 65 years old with acute upper respiratory tract infection and a fever higher than 38 ºC. Onset of illness within 48 hours. Diagnosed as TCM signs 'chills cold'. There were 90 people in the intervention group (M/F = 41/49. The onset of cold symptoms was within 24 hours for 67 participants, and within 48 hours for 23 participants. Status of disease: light/moderate/heavy: 18/61/11). There were 30 people in the control group (M/F = 16/14. The onset of cold was within 24 hours for 18 participants, and within 48 hours for 12 participants. Status of disease: light/moderate/heavy: 6/20/4).
Interventions	Sanhanjiere Koufuye was used in the intervention group; oral 10 ml, t.i.d. for 3 days Biaoshi Ganmao Chongji was used in the control group; oral drink 10 g dissolved in water, t.i.d. for 3 days
Outcomes	Observations for temperature and symptoms. TCM symptoms were evaluated as scores. 1. Recovery 2. Marked improvement 3. Improvement 4. Inefficacy 5. Adverse events were sorted into 5 categories: related, maybe related, maybe no relationship, no relationship and cannot identify All outcomes included TCM symptoms scores showing there were no statistically significant differences between the 2 groups
Notes	1. This was a clinical study for new drug development 2. Funded by manufacturer 3. "Positive drug" Biaoshi Ganmao Chongji was the control, but no evidence of its effectiveness was recorded 4. No statement for sample size calculation 5. All signs were compared. There were no statistically significant differences between the 2 drugs. We did not calculate these data ourselves, but used the original results.
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate

Chang 2005.

Methods	Parallel positive drug control design. Block randomisation was performed by centre unit and the random sequence was generated by SAS 6.12 Proc PLAN and concealed adequately. Both intervention provider and participants were blinded.
Participants	240 patients were included. 120 patients were randomly allocated to the capsule group and 120 to the granule group. Patients were included according to the diagnostic criteria of acute upper respiratory tract infection and fever. Onset of illness within 48 hours and did not use any drug treatment. Participants were aged 18 to 65 years old and signed a consent form. Patients with any positive laboratory findings including an increased WBC count, combined with pharyngitis, herpes pharyngitis, influenza, acute obstruction of the throat‐trachea‐bronchitis, capillary bronchitis and pneumonia. People with heart, brain, liver, kidney and circulatory system diseases were excluded. In addition, 4 patients dropped out in the capsule group; and there were 8 drop‐outs and 3 losses to follow up in the granule group. Thus, there were 116 patients in the capsule group and 110 in the granule group for PP analysis. Baseline was similar.
Interventions	Jin Lian Qin Re capsule group: orally 4 capsules t.i.d. plus granule simulation 1 bag at a time t.i.d. Jin Lian Qin Re granule group: orally 1 bag at a time t.i.d. plus 4 simulation capsules t.i.d. Treatment was a 3‐day course
Outcomes	Symptoms assessed included fever and a heightened dislike to wind and cold, pharyngalgia, cough, expectoration, nasal obstruction, rhinorrhoea and thirst. Body signs assessed included tonsil and pharynx hyperaemia, tumefaction and secretion, lingual surface map, and change of pulse rate/rhythm. Toxicity and adverse reactions were observed by laboratory tests. Outcomes were judged based on the changing of symptoms and body signs and divided into the following categories: 1. Recovery: TCM symptoms disappeared or almost disappeared, signs scores reduced more than 95% 2. Marked improvement: TCM symptoms markedly improved, TCM signs scores reduced more than 70% 3. Improvement: partial TCM signs improved, signs scores reduced more than 30% but less and 70% 4. No improvement: TCM signs no improvement or worse, signs scores reduced less than 30% 5. TCM signs 6. Time for fever reduction to start: time temperature took to decrease 0.5 ºC after taking the drug 7. Time of fever clearance: time needed for the fever to disappear without recurrence 8. Virus clearance 9. Adverse events: definitely related, high possibility related, maybe related, no relationship. Definitely related, high possibility related and maybe related are judged to be adverse events.
Notes	1. This study was funded by a pharmaceutical company 2. This was a phase II clinical trial for new drug development 3. The control was a drug that the public considered to be effective, but it actually was the intervention drug in a different form: Jin Lian Qin Re granule. No evidence was searched from any clinical trial. 4. Sample size calculation was not performed but was according to SFDA's rule 5. There was no description of who performed the generation of random sequence 6. The article described blinding as being performed to the 'researcher', participants, 'detector' and data input person throughout the duration of the study 7. Both ITT and PP analysis were used
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate

Chang 2007.

Methods	Multi‐centre, double blinded, parallel positive drug control design. Block randomisation was performed by centre unit and the random sequence was generated by SAS 6.12 Proc PLAN and concealed adequately
Participants	In phase II, 60 patients aged 18 to 65 years old with acute upper respiratory tract infection were randomly divided into the trial group (n = 30) and the control group (n = 30). In phase III, 112 patients were randomly divided into the trial group (n = 84) and the control group (n = 28). Patients were included according to the diagnostic criteria of acute upper respiratory tract infection and fever. Onset within 48 hours and never used any drug
Interventions	The intervention group were given Chaige Qingre granule, 1 bag (6 g) at a time, q.i.d. The control group were given Fufang Shuanghua granule, using the same method as the intervention group. Treatment lasted for 3 weeks.
Outcomes	Outcomes were judged based on the changing of symptoms and body signs. They were sorted as: 1. Recovery: TCM symptoms disappeared or almost disappeared, signs scores reduced more than 90% 2. Marked improvement: TCM symptoms markedly improved. TCM signs scores reduced more than 75% but less and 90% 3. Improvement: partial TCM signs improved, signs scores reduced more than 50% but less and 75% 4. No improvement: TCM signs no improvement, body temperature did not decrease or increase within 3 treatment days 5. TCM signs 6. Adverse events: definitely related, high possibility of being related, maybe related, no relationship. Definitely related, high possibility of being related and maybe related are judged to be adverse events
Notes	1. This was a clinical trial of phase II and phase III for new drug development, and funded by a pharmaceutical company 2. Fufang Shuanghua granule, "public considered positive effective drug" was selected as control, but no record about its effect from a RCT was found 3. Sample size calculation was described in detail 4. Toxicity or adverse effects were observed; all of the laboratory data were presented 5. TCM signs were reported, we used the results directly 6. Both ITT and PP analysis were used
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate

Chen 2004.

Methods	Multi‐centre, parallel design. The randomisation method was not mentioned in the original article so we telephoned the trial author. A random numbers table was used to generate the allocation sequence. Single blinding was used for the children.
Participants	Total 140 participants aged 3 to 14 years with acute upper respiratory tract infection. TCM symptoms sorted as fever cold were included. It was not clear how many children in each group exactly. At the end of the trial, 4 children dropped out; 66 in Gegen Chen Lian Wei Wan group and 70 in control group. The term 'similar on baseline' was mentioned but no data were presented in detail.
Interventions	The intervention group were given Gegen Chen Lian Wei Wan, a finished product of Chinese herbs. 3 to 7 year olds were given 1 g and 7 to 14 year olds were given 2 g t.i.d. The control group were given Yinqiaojiedu Pian tablet a "positive effect" finished product of Chinese herbs. 3 to 7 year olds were given 2 tablets and 7 to 14 year olds given were 3 tablets t.i.d.
Outcomes	1. Recovery 2. Marked improvement 3. Improvement 4. Inefficacy 5. The time at which fever reduction started 6. Fever clearance time 7. TCM symptom scores and tongue map 8. Virus test 9. White blood cell count 10. Safety
Notes	1. The "positive drug" Yinqiaojiedu Wan was used as the control, but there is no evidence of effectiveness of this drug for treating common cold 2. Data on the time period before fever reduction started, fever clearance time, TCM symptom scores, WBC count and safety are not presented in detail 3. This was a trial for a new drug development and was funded by a pharmaceutical company 4. There was no information about the sample size calculation
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	D ‐ Not used

Li 1998.

Methods	Randomisation method not mentioned in the original article. We telephoned the trial author and found out that a random numbers table was used to generate the allocation sequence. There was no blinding
Participants	A total of 463 children aged 6 months to 14 years with common cold (TCM syndrome as fever cold), onset within 48 hours, not treated by other medications, without high fever convulsions. 311 children were allocated to the intervention group and 152 to the control group
Interventions	Qinwinkeli was given to the intervention group and Kangbingdu Koufuye to the control group. There was no more information about treatment
Outcomes	Scores were given based on the severity of temperature and symptoms: less than 19 points as slight, 20 to 26 points as moderate, more than 27 points as heavy 1. Recovery 2. Marked improvement 3. Improvement 4. Inefficacy
Notes	1. This was a clinical study for new drug development, and was funded by a pharmaceutical company 2. This was a local government supported project 3. The formulation of the drug was provided by the author's department 4. The control drug was Kangbingdu Koufuye, but the RCT provided no evidence of its effectiveness in treating common cold 5. There was no information about the sample size calculation
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	D ‐ Not used

Li 1999a.

Methods	Multi‐centre (8 hospitals) parallel design Randomisation method not described in the original article. We telephoned the author and learned that the allocation sequence was generated by computer software. There was no blinding
Participants	400 participants with acute upper respiratory tract infections were enrolled. 178 males and 131 females aged 35.74 +/‐ 14.61 years were allocated to 3 intervention groups (108 to the 120 ml group, 111 to the 160 ml group and 90 to the 200 ml group). Of them, there were 19 patients with slight fever (37.5 to 37.9 ºC), 123 with moderate fever (38.0 to 38.9 ºC) and 167 with high fever (higher than 39.0 ºC). 91 participants were allocated to the control group including 52 males and 39 females aged 31.87 +/‐ 12.92 years. Of them, 9 with slight fever, 43 with moderate fever and 39 with high fever
Interventions	The intervention group was given Qinkailing injection: 120 ml, 160 ml, and 200 ml/day diluted in 1000 ml of 5% to 10% glucose infusion or 0.9% saline infusion. After infusion with 500 ml of the drug, another 500ml of 5% to 10% glucose, glucose in normal saline or 0.9% sodium chloride solution was injected as a buffer and then continued with the rest of the drug. The above 1500 ml solution was regularly given once a day and 3 days of treatment was taken as 1 course The control group used lincomycin 1.8 g /day; the method used was the same as in the intervention group
Outcomes	1. Relationship of dose and effects 2. The time period before temperature decreased by 0.5 °C 3. Relationship of length of disease and effects in Qinkailing group only 4. WBC count 5. Throat swab for bacteria test (only included in 22 cases) 6. Results were reported as recovery, marked improvement, improvement and inefficacy
Notes	1. This was a trial for new drug development and was funded by a pharmaceutical company 2. There was no evidence provided of the effectiveness of the control drug lincomycin for common cold 3. There was no information about the sample size calculation
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	D ‐ Not used

Liu 2002.

Methods	"Randomly allocated" was mentioned but no detail about the method. We telephoned the authors and learned that a random numbers table was used to generate the allocation sequence. There was no blinding
Participants	100 children aged 3 to 12 years old were equally allocated into 2 arms. Temperature 38 to 39 ºC. Baseline characteristics of age, gender, symptoms and signs between the 2 groups were similar
Interventions	Kangbingdupian tablet group: 3 to 6 years old, 2 tablets at a time; 6 to 9 years old, 3 tablets at a time; 9 to 12 years old, 4 tablets at a time, t.i.d. Control group: oral Banlangen Chongji, 3 to 6 years old 5 g, 6 to 12 years old 10 g t.i.d. Both groups used the same allopathy for clinical symptoms
Outcomes	1. Marked improvement: temperature normalised and clinical symptoms and signs disappeared within 3 to 5 days after starting treatment 2. Improvement: temperature normalised within 3 to 5 days after starting treatment, clinical symptoms and signs markedly improved 3. Inefficacy: there was no change after 5 days
Notes	There is no evidence of effectiveness of the control drug Banlangen Chongji for treating common cold
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	D ‐ Not used

Ma 2000.

Methods	Randomisation method was not described in the original article. We telephoned the author and learned that a random numbers table was used to generate the allocation sequence. There was no blinding
Participants	101 boys and 107 girls aged 3 to 13 years were randomly allocated into the intervention group. Of them, the average age was 6.03 +/‐ 2.27. Length of time that they had been suffering from the common cold was 4 to 70 hours, and the average time was 29.33 +/‐ 10.32 hours; 140 children had fever 33 boys and 35 girls were allocated into the control group, of them, aged 3.5 to 14 years (average 6.13 +/‐ 2.13); time of suffering disease 3 to 72 hours (average 31.78 +/‐ 10.59 hours); 44 children with fever
Interventions	Shuanghua aerosol was used in the intervention group: 8 ml/day, spray throat 8 times a day, push 4 to 6 times; total 3 days Shuanghuanglian aerosol was used as the control. The usage was as per the intervention group
Outcomes	1. Recovery 2. Marked improvement 3. Improvement 4. No improvement 5. Comparison for course of recovery cases: intervention group (136 cases) 52.51 +/‐ 10.97, control group (30 recovered) 57.49 +/‐ 11.30 6. Time of clearing the fever in recovered fever patients: intervention group (118 cases) 30.21 +/‐ 14.89 hours, control group (32 cases) 38.67 +/‐ 13.56 hours
Notes	1. This was a local government (He Nan province) supported project 2. The formulation of Shuanhua aerosol was provided by authors themselves 3. The product of Shuanghua aerosol was made by trial author's hospital 4. No evidence about effect of control drug Shuanghuanglian aerosol was found 5. No statement for sample size calculation
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	D ‐ Not used

Pan 2000.

Methods	"Randomly allocated" was mentioned but lack of description about the method. We telephoned the author and learned that they used a computer to generate the allocation sequence. The participants were blinded to the drugs
Participants	120 children with fever (higher than 37.5 ºC) after onset the disease no more than 2 days. 60 children in intervention group, 32 boys and 28 girls (3 children < 1 year, 25 were 1 to 3 years, 18 were 3 to 7 years, and 14 were 7 to 13 years) 60 children in control group included 38 boys and 22 girls (8 children < 1 year, 19 were 1 to 3 years, 19 were 3 to 7 years, and 14 were 7 to 13 years) Anyone who also had lower respiratory tract infection, for example severe bronchitis or pneumonia, was excluded
Interventions	Xiao‐er Reganning for intervention group; the first dose was taken orally with 2 folder than the general dose; then children < 1 year took 2.5 to 5 ml, 1 to 3 years 5 to 10 ml, 3 to 7 years 10 to 15 ml, 7 to 13 years 15 to 20 ml Wei C Yinqiao Pian (Vitamin C with Yinqiao) was given in control group: 1/3 package/time for < 1 year children, 1/2 package/time for 1 to 3 years, 2/3 package for 3 to 7 years, and 1 package for 7 to 13 years children. 3 times a day; total 3 days
Outcomes	1. Marked improvement: temperature cleared and the symptoms including sore throat and cough showed marked improved within 3 days after treatment 2. Improvement: temperature not been cleared (37 to 37.5 ºC axillar temperature) at day 3 after treatment, symptoms slightly improved 3. No improvement
Notes	1. This was a new drug clinical effects assessment study 2. The authors prepared the drug formulation themselves 3. The drug was made by author's hospital 4. The study was supported by local government (Guanxi province), therefore there was conflict of interest between authors and study 5. There is no evidence about effect of vitamin C Yinqiao Pian for common cold 5. There was no statement about sample size calculation
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	D ‐ Not used

Song 2004a.

Methods	"Random allocation" was mentioned but lack of description about the method. We telephoned the author and learned that a random number table was used to generate the allocation sequence. There was no blinding
Participants	60 children were equally allocated to 2 groups. Baseline characteristics of the 2 groups, including gender, age and state of illness, were similar
Interventions	The treatment group received self‐prepared TCM cream applied on the "Shen Que" point in 3 g, 5 g, 7 g and 10 g doses according to age; every 6 hours fresh cream was applied. The duration of treatment was 3 to 5 days The control group received penicillin or lincomycin Both groups used ataractic, antitussive and acetanilide if necessary
Outcomes	1. Recovery: temperature normalised within 24 to 48 hours after starting treatment; all TCM signs disappeared 2. Marked improvement: temperature normalised within 24 to 48 hours after starting treating; most TCM signs disappeared 3. Improvement: temperature normalised within 48 to 72 hrs after starting treatment 4. Inefficacy
Notes	1. Both drug formulation and preparation were self‐prepared by author 2. There was no statement explaining sample size calculation 3. There is no evidence about the effectiveness of penicillin or lincomycin for common cold yet
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	D ‐ Not used

Wang 1998.

Methods	Randomisation method was not described in the article. We telephoned the original trial author and the method was described as "mo qiu" which means that children or their parents take a little coloured ball from an opaque box to decide which group they will be in. The method was judged adequate randomisation. There was no blinding
Participants	70 children aged 6 months to 3 years with acute respiratory tract infections (including the symptoms fever, cough, expectoration, vomiting and diarrhoea) were randomly allocated to 2 groups, each group contained 35 children. The baseline characteristics of the 2 groups were similar
Interventions	The intervention group were given Jianer Qinjieye orally. Infants (6 months to 1 year) and young children (1 to 3 years) received 4 ml and 10 ml doses respectively t.i.d. The control group were given Qinre Jiedu Koufuye orally at the same dose as the intervention group
Outcomes	Outcomes observed: 1. Improvement of symptoms, including, fever, cough, expectoration, vomiting and diarrhoea 2. Temperature 3. Throat 4. Tonsil 5. Peripheral blood cell count and cytotaxonomy Scores were judged on the symptoms categories Outcomes: 1. Recovery 2. Marked improvement 3. General improvement 4. Inefficacy 5. Side effects and adverse effects
Notes	1. 4 children in intervention group and 5 in control group dropped out, therefore 31 children in the intervention group and 30 in the control group completed the study 2. This was a study for new drug development and was funded by a pharmaceutical company 3. Qinrejiedu Koufuye was used as the "positive" control, but there is no evidence of its effectiveness in treating common cold 4. There was no statement on the sample size calculation
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	D ‐ Not used

Wang 2004.

Methods	"Random allocation" was mentioned but there was no method described. We telephoned the trial author and learned that a random numbers table was used to generate the random sequence. Double blinding was used for the patients and drug provider. Parallel group design
Participants	People with "chill cold", aged 18 to 65 years old, no more than 2 days after cold onset. 310 patients were randomly allocated to the intervention group and 107 to the control group. The baseline characteristics of the 2 groups were similar
Interventions	People in the intervention group were given Sufeng Ganmao Koufuye orally, 10 ml, t.i.d. for 3 days People in the control group were given Ganmao Qingre Koufuye, 10 ml, t.i.d. for 3 days
Outcomes	Symptom scores were calculated according to the presence of fever, headache, body pain, snuffles, running nose and cough to group the subjects into light, moderate and heavy levels Recovery, marked improvement and no improvement were evaluated according to the symptom scores. Liver function, kidney function, WBC count, electrocardiogram and other factors (not defined in detail) were used to estimate adverse events. Results also included scores comparison, but the data could not be used for analysis due to absence of standard deviation. TCM symptoms were also evaluated
Notes	1. This was a phase III study for new drug development 2. A pharmaceutical company provided funding for the trial 3. "Positive control" Ganmao Qingre Koufuye was used as the control, but we did not find any record about this drug anywhere 4. Due to the absence of standard deviation, continuous data cannot be used for analysis 5. No statement on the sample size calculation 6. TCM signs were reported, and data were extracted and analysed
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate

Wang 2008a.

Methods	Multi‐centre (5 hospitals), double blinded, double‐dummy, parallel positive drug control design. Block randomisation was performed by centre unit and the random sequence was generated by SAS 6.12 Proc PLAN and concealed adequately
Participants	360 patients were randomly divided into treatment group A (n = 120 treated with Yiqing Shuangjie Capsule and Chaihuang analogues), treatment group B (n = 120 treated with Yiqing Shuangjie Tablet and Chaihuang analogues) and the control group (n = 120 treated with Chaihuang tablet and Yiqing Shuangjie Capsule analogues). Baseline data between the 2 groups on age, gender, symptoms and signs were similar
Interventions	Yiqing Shuangjie capsule was used in intervention group A, Yiqing Shuangjie tablet was used in intervention group B Control group used Yiqing Shuangjie tablet and Yiqing Shuangjie capsule analogues; the method used was the same as the intervention group Every drug was administered as 3 pills for each dose. Patients in the 3 groups were all treated for 5 days and 3 times daily
Outcomes	Symptoms assessed included fever and a heightened dislike of wind and cold, pharyngalgia, cough, expectoration, nasal obstruction, rhinorrhoea and thirst. Body signs included tonsil and pharynx hyperaemia, tumefaction and secretion, lingual surface map, change of pulse rate/rhythm Laboratory tests for observation for toxicity and adverse reaction. Outcomes were judged based on the changing of symptoms and body signs. They were divided into the following categories: 1. Recovery: TCM symptoms disappeared or almost disappeared, signs scores reduced more than 95% 2. Marked improvement: TCM symptoms markedly improved, TCM signs scores reduced more than 70% 3. Improvement: partial TCM signs improved, signs scores reduced more than 30% but less than 70% 4. No improvement: TCM signs showed no improvement or worsening, signs scores reduced less than 30% 5. TCM signs 6. Time fever reduction started: the time the temperature took to decrease 0.5 ºC after taking the drug 7. Time of fever clearance: time needed to the fever clearance without recurrence 8. Virus clearance 9. Adverse events: definitely related, high possibility related, maybe related, no relationship. Definitely related, high possibility related and maybe related are judged to be adverse events
Notes	1. This was a phase II clinical trial for new drug development, and was funded by a pharmaceutical company 2. Chaihuang tablet, considered by the general public to be an 'effective drug', was selected as the control, but there is no record of its effectiveness 3. Sample size calculation was described in detail 4. Toxicity or adverse effects were observed, all of the laboratory data were presented 5. TCM signs were reported; we used the results directly 6. Both ITT and PP analysis were used
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate

Yang 2000.

Methods	Parallel design. Random number table was used to generate the allocation sequence. Double blinded
Participants	60 children with acute respiratory tract infection with fever (M/F = 32/28, aged 11 months to 14 years, average 4.83 +/‐ 2.53 years, temperature 38.83 +/‐ 1.32 °C, length of disease been 1.57 +/‐ 0.51) were randomly allocated to the intervention group 31 children (M/F = 16/15, aged 11 months to 12 years, 4.53 +/‐ 2.21 years, temperature 38.79 +/‐ 1.17 °C, length of disease 1.34 +/‐ 0.63 days) were allocated to the control group
Interventions	The intervention group received Huanghujiere bag tea. Half of a bag b.i.d. was given to children less than 12 months, 1 bag b.i.d. for children aged 1 to 5 years, and 1 bag t.i.d. for children aged 6 to 14 years The control group received Shiqiganmao bag tea in the same way as the intervention group Duration of treatment in both groups was 5 days
Outcomes	1. Recovery 2. Marked improvement 3. Improvement 4. Inefficacy 5. Average fever clearance time 6. Toxicity and adverse effects; no adverse effects were observed
Notes	1. None of the laboratory data were presented 2. No toxicity or adverse effects were observed 3. Except for the improvement of overall symptoms, data for other outcomes were unusable 4. The control drug has not yet been evaluated systematically 5. The formulation of Huanghu Bag tea was prepared by the authors themselves and was made by the authors' hospital 6. This project including clinical trial was funded by Guangzhou local government 7. Shiqiganmao bag tea was used as the control, but there is no record of its effectiveness 8. There was no statement on sample size calculation
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	D ‐ Not used

Yu 1997.

Methods	Parallel design. Randomisation method not described. We interviewed the original author by telephone and learned that a random numbers table was used to generate allocation sequence, and both the allocation process and the sequence were not masked. There was no blinding
Participants	Children with acute upper tract infections with length of disease no longer than 3 days. Patients with acute suppurative tonsillitis, congenital hypoplasia or malnutrition were excluded. 43 children (21/22 M/F, 6 months to 5.5 years old, course 1.46 +/‐ 0.69 days, temperature 39.2 °C) were randomly allocated to receive enema lavage solution; 15 children (6/9, M/F, 6 months to 5 years, length of disease 1.36 +/‐ 0.61 days, temperature 39.4 + 0.42 °C) were allocated to receive Western medicine (WM)
Interventions	Chaiqin Qinre enema lavage solution in the intervention group: each ampoule contains 4 ml, 1 ampoule for children younger than 4 years inserted into rectum and 2 ampoules for children older than 4 years, 3 times a day WM group: virazole IM, 15 mg/kg paracetamol injection 10 mg/kg, t.i.d., 3‐day course. Licormixture was given to patients from both groups with cough
Outcomes	1. Recovery 2. Marked improvement 3. Improvement 4. Inefficacy 5. Rates of effect 6. Assessment for effects according to stratified by TCM and WM 7. Effects were also reported according to TCM signs 'fever cold' and 'chilly cold', but not described in detail
Notes	1. Data from stratified analysis of effects on TCM symptoms were unusable 2. This was a Shanghai local government supported project 3. Chaiqin Qinre enema lavage solution was made in the author's hospital 4. There is no evidence of the effectiveness of virazole for the common cold 5. There was no statement on sample size calculation
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	D ‐ Not used

Yu 2005.

Methods	Parallel design. Randomisation method not mentioned in published article. We telephoned the author and learned that a random number table was used to generate the random sequence. There was no blinding
Participants	Patients with chill type common cold were included. Intervention group: 30 patients (including 10 outpatients, 20 inpatients) M/F = 14/16, average age 37.1 years (19 to 64); 13 persons with temperature 38 to 38.9 °C, 15 with 39 to 39.8 °C, 2 with temperature higher than 40 °C Control group: 30 patients, including 11 outpatients, 19 inpatients, M/F = 12/18, average age 35.4 years (18 to 64); 12 persons with temperature 38 to 38.9 °C, 17 with 39 to 39.8 °C, 1 with temperature higher than 40 °C
Interventions	Sanhan Jiere Koufuye was used in intervention group, oral 1 ampoule (10 ml), t.i.d. for 3 days; Biaoshi Ganmao Chongji for control group, oral drink 1 bag (10 g) solved in water, t.i.d. for 3 days
Outcomes	1. Recovery 2. Marked improvement 3. Improvement 4. Inefficacy 5. TCM signs: 3 signs including fever, chill and lack of sweat were better in the intervention group than in the control group; no difference between the 2 groups was found for the other 5 symptoms including headache, cough, etc. 6. Adverse events: no difference was found 7. Fever clearance time
Notes	1. This was a clinical study for new drug development 2. The formulation of Shanhan Jiere Koufuye was designed by a TCM doctor from the authors' hospital 3. Biaoshi Ganmao Chongji was used as the control, but no clinical trial was found 4. No statement on sample size calculation
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate

Zhang 2008.

Methods	Multi‐centre (6 hospitals), double blinded, parallel control design Randomisation method not described in original article. We telephoned the author and learned that the allocation sequence was generated by computer software and concealed adequately
Participants	240 participants with upper respiratory tract infections (wind cold syndrome) were included. 120 were randomly allocated to intervention group (2 patients dropped out) and 120 were in the control group (9 patients dropped out). 118 patients in the intervention group: M/F = 78/40, average age 31.09 +/‐ 12.5 years (18 to 63) and 114 in the control group. Baseline characteristics of the 2 groups were similar
Interventions	Qinyin injection was used in the intervention group, 30 ml a day, diluted with 5% glucose 250 ml iv drip q.i.d. and 5% GNS 250 ml iv drip q.i.d. given within 1.5 to 2 hours Control group received Qingkailing injection; the method used was the same as the intervention group. The interval of 2 doses was at least 12 hours for 2 continuous days, and lasted 3 days
Outcomes	Laboratory test observation for safety. 1. Blood routine tests (WBC, RBC, HGB) 2. Urine routine tests 3. Stool routine tests 4. Liver function (ALT, AST) 5. Renal function(Cr, BUN) 6. ECG 7. PT, APTT
Notes	1. This was a phase II clinical trial for new drug development, and funded by a pharmaceutical company 2. "Positive control " Qingyin injection was selected as control, but RCT about its effect was found 3. No statement on sample size calculation 4. Toxicity or adverse effects were observed; all of the laboratory data were presented 5. ITT analysis was not used
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate

ALT: Alanine transaminase 
 APTT: activated partial thromboplastin time 
 AST: Glutamic oxalacetic transaminase 
 b.i.d: twice a day 
 BUN: blood urea nitrogen 
 Cr: creatinine 
 ECG: electrocardiogram 
 GNS: glucose and sodium chloride injection 
 HGB: haemoglobin 
 IM: intramuscular 
 ITT: intention‐to‐treat 
 iv: intravenous 
 M/F: male/female 
 PP: per‐protocol 
 PT: prothrombin time 
 q.i.d.: four times a day 
 RBC: red blood cell 
 SFDA: State Food and Drug Administration 
 t.i.d.: three times a day 
 TCM: traditional Chinese medicine 
 WBC: white blood cell 
 WM: Western medicine

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion
Bao 2000a	Described as a 'randomised controlled trial'. We telephoned the original author and learned that this was actually a retrospective paper and a summary of the author's clinical experience
Bao 2000b	The second version of Bao 2000a
Bao 2001	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by author
Bao 2003	Described as a 'randomised controlled trial'. We telephoned the original author and learned that the allocation method was according to the order the patients came to the hospital
Cai 1994	Described as a 'randomised controlled trial'. We telephoned the original author and learned that the allocation method was "random sampling"
Cai 2007	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by author optionally
Cao 1994	Described as a 'randomised controlled trial'. We telephoned the original author and learned that the patients were allocated according to the order patients came to hospital
Cao 1998	Described as a 'randomised controlled trial'. We telephoned the original author and learned that the patients were allocated "basically" according to the order they came to hospital
Cao 2003	Described as a 'randomised controlled trial'. We telephoned the original author and learned that the method of allocation was not randomised
Chen 1994	Described as a 'randomised controlled trial'. The original author refused our telephone interview
Chen 1995	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the allocation of patients was performed optionally
Chen 1997	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated according to the order they came to the hospital
Chen 2001	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the answer was "no, I don't know how to allocate the patients". Thus, this study was considered a non‐RCT
Chen 2004a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated optionally
Chen 2004b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned about that the patients were allocated optionally
Chen 2004c	Described as a 'randomised controlled trial'. We telephone interviewed the original author, but he could not verify the randomisation method
Chen 2005a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the randomisation procedure was stated to be "order of patients to see the doctor"
Chen 2005b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were actually allocated optionally
Chen 2005c	The second version of Chen 2004b
Chen 2005d	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that this was a retrospective study about the author's clinical experience
Chen 2007a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the allocation was performed optionally
Chen 2007b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated based on their birth date
Chen 2007c	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the doctor optionally
Chen 2007d	Described as a 'randomised controlled trial'. We telephoned the original author and learned that the allocation method was according to the order of patients coming to the hospital
Chen 2007e	Described as a 'randomised controlled trial'. The original author acknowledged that it was a retrospective paper
Chen 2008	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated based on their bed number
Cheng 1997	Not only common cold, but 23 patients with acute laryngotracheitis were included. The data could not be separated for analysis
Cheng 1999	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the allocation was performed optionally
Cong 2005	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients had actually been allocated optionally
Cui 2007	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by the author optionally
Dai 1997	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the randomisation was stated to be "not performed exactly according to the rule"
Dai 2001	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the allocation was performed optionally
Deng 2001	Stated "randomly allocate patients into two groups". Since the original author refused our telephone interview, we could not gain any information about randomisation to judge its validity
Deng 2002a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned the "random sampling" was used to allocate patients
Deng 2002b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that allocation was according to date of admission
Deng 2007	Described as a 'randomised controlled trial'. We telephone interviewed the original author who acknowledged that it was a retrospective paper
Di 2004	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the doctor optionally
Diao 2003	A version of Jiang 2003a
Dong 2002	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated optionally
Du 2003	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated based on their bed numbers
Duan 1995	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned the patients were allocated on the order of their admission
Duan 2007	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the allocation for patients was performed optionally
Fan 2007	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated optionally
Fu 2002	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by the author optionally
Gan 2000	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that this was a retrospective paper
Gao 1999a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated according to the order of admission
Gao 1999b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated according to the order of admission
Gao 2000	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the allocation method was described as "randomly select patients as control"
Gu 2005b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated according to the order of admission
Guan 2001	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the author optionally
Guo 2000a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the allocation method was described as according to the order of admission
Guo 2003a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated optionally.
Guo 2003b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that children were allocated by the doctors optionally
Guo 2007	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the allocation was performed optionally
Guo 2008a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned the patients were allocated by order of admission
Guo 2008b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned about that the patients were allocated optionally.
Han 2002	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the doctors optionally
Han 2004	Described as a 'randomised controlled trial'. We telephone interviewed the original author but they refused the interview
Han 2008	Described as a 'randomised controlled trial'. The original author stated during the telephone interview that the randomisation procedure was not performed exactly
He 1999a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated according to the order of admission.
He 1999b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the authors optionally
He 2003	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by the author optionally
Hou 2001a	Combined Yiqin capsule with antibiotics did not match our inclusion criteria
Hou 2001b	The second version of Hou 2001a
Hu 2003	Combined with other intervention Xiaper‐Xuxiao Ganmaoning
Hu 2005	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the author optionally
Hu 2007b	It was claimed 'RCT. We telephone interviewed the original author and the randomisation was stated as "not performed exactly according to the rule".
Hua 2000	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated optionally.
Huang 2001	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by the authors optionally
Huang 2008	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the allocation was performed optionally
Ji 2000	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by authors optionally
Ji 2002	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the authors optionally
Ji 2004	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated according to the date of admission.
Ji 2008	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by the author optionally
Jia 1997	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the randomisation procedure was described as "random sampling"
Jiang 2000	Described as a 'randomised controlled trial'. The author answered that "we did not perform randomisation exactly" when we performed telephone interview
Jiang 2001	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the author optionally.
Jiang 2002	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the author optionally
Jiang 2003a	Half of the included patients suffered from influenza rather than the common cold
Jiang 2004	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated optionally
Jiang 2005	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the authors optionally
Jiang 2007	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients had actually been allocated optionally
Jin 2000	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated according to the date of admission
Jin 2001	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the authors optionally
Jin 2007	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the randomisation was described as "not performed exactly according to the rule".
Jing 2007	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by the author optionally
Ju 2002	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the author optionally
Ke 2007	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the allocation was performed optionally
Kong 2000	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by the authors optionally
Lai 2000	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the authors optionally
Lan 2005	Described as a 'randomised controlled trial'. We telephone interviewed the original author and confirmed that this was a retrospective paper
Li 1994	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the authors optionally
Li 1997	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the author optionally
Li 1998a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the authors optionally
Li 1998b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that children in the control group were "randomly sampled" from outpatients
Li 1998c	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by the authors optionally
Li 1998d	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by the authors optionally
Li 1999b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the randomisation method an inadequate method, "Chouqian"
Li 1999c	Described as a 'randomised controlled trial'. The original author refused our telephone interview
Li 2000a	Claimed 'RCT'. The original author acknowledged that it was a retrospective paper
Li 2000c	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the authors optionally
Li 2002c	Self‐prepared formulation and described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by drawing lots
Li 2003a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the patients were allocated by "random sampling"
Li 2003b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients where allocated by the authors optionally
Li 2003c	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the randomisation method found to be an inadequate method, "Chouqian"
Li 2003d	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by "Chouqian" but not an adequate method
Li 2003e	Described as a 'randomised controlled trial'. The original author stated during the telephone interview that the randomisation procedure was not performed exactly.
Li 2003f	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the authors optionally
Li 2003h	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated optionally
Li 2007a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by the author optionally
Li 2007b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by the author optionally
Li 2007c	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by the author optionally
Li 2007d	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the randomisation procedure was stated to be "order of patients to see the doctor"
Li 2007e	The second version of Wu 2007
Li 2008	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the doctor optionally
Lian 2001	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the authors optionally
Liang 1998	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the allocation was performed optionally
Liang 2007	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the allocation was performed optionally.
Liao 2004a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the authors optionally.
Liao 2004b	The second versions of Liao 2004b
Lin 1999a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by the authors optionally.
Lin 2002	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated optionally.
Lin 2004	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the allocation method was described as according to the admission order.
Ling 2007	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the allocation was performed optionally.
Liu 2000	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the randomisation method was described as "Chouqian" (lot).
Liu 2001b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned the patients were allocated by the authors optionally.
Liu 2001c	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the authors optionally.
Liu 2003	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the authors optionally.
Liu 2004a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated according to the admission order.
Liu 2004b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated according to the order of admission.
Liu 2004c	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the allocation method was described as "random sampling".
Liu 2008a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the allocation was performed optionally.
Long 2000	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the allocation method was described as "random sampling".
Lu 2000	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the allocation procedure was described as "depended on the admission number".
Lu 2001	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the allocation was stated to be "according to admission order but not exactly".
Lu 2005	Described as a 'randomised controlled trial'. We telephone interviewed the original author who stated "that was optional" about the allocation method.
Lu 2007	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated according to the order they came to the hospital.
Luo 2008	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by the author optionally.
Lv 2007	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the allocation was performed optionally.
Ma 1996	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the allocation method was described as "random sampling".
Ma 2002a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the author optionally.
Ma 2002b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the randomisation procedure was described as "according to admission order but not exactly".
Ma 2005	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the authors optionally.
Meng 2007	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by the author optionally.
Miu 2002	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the authors optionally.
Mu 2004	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the author optionally.
Ou 1996	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the allocation method was described as "random sampling".
Pan 1999	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the allocation method was described as "according to admission order".
Pan 2001a	Multiple versions of included study Pan 2000
Pan 2001b	Multiple versions of included study Pan 2000
Pan 2002a	Multiple versions of included study Pan 2000
Pan 2002b	Multiple versions of included study Pan 2000
Pan 2002c	Multiple versions of included study Pan 2000
Pan 2003	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the allocation method was described as "random sampling".
Pang 2003	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the allocation method was described as "random sampling".
Qi 2000	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the randomisation procedure was stated as "Chouqian (drawing lots)".
Rao 1999	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the author optionally.
Ren 2007	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by the author optionally.
Ruan 2007	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated according to the date of admission.
Shi 1998b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the allocation method was described as "according to admission order".
Song 2004b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the authors optionally.
Song 2008	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned about that the patients were allocated optionally.
Sun 1995	Described as a 'randomised controlled trial'. The number of children in the three arms were 106/83/24; it therefore was judged to be optional allocation.
Sun 1997	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the patients were allocated by the authors optionally.
Sun 1999b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the authors optionally.
Sun 2003a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that this was a retrospective paper.
Sun 2003b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the authors optionally.
Sun 2007	The same as multi‐centre clinical trial Zhang 2008
Tang 2000	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the allocation method was described as "random sampling".
Tang 2003	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated according to their age.
Tang 2005	Described as a 'randomised controlled trial' and the allocation method was described as "according to odd or even number".
Tang 2007	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the doctor optionally.
Tao 2007	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the allocation was performed optionally.
Tian 1998	Described as a 'randomised controlled trial'. We telephone interviewed the original author to identify which method of randomisation was used in the trial. From the author's description we judged it actually was a non‐RCT.
Tong 2004	Described as a 'randomised controlled trial'. We telephone interviewed the original author, and learned that the paper was written by another person as a gift given to Dr. Tong. Dr. Tong herself do not know anything about the study.
Wan 2003	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the authors optionally.
Wang 1995a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the authors optionally.
Wang 1995b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and confirmed it was a retrospective paper.
Wang 1996a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated according to the admission sequence.
Wang 1996b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the author optionally.
Wang 1997a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the authors optionally.
Wang 1997b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the authors optionally.
Wang 1997c	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated according to the admission order.
Wang 1999a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the authors optionally.
Wang 2001a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the authors optionally.
Wang 2001b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the authors optionally.
Wang 2001c	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that it was a retrospective paper.
Wang 2001d	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the randomisation was described as "random sampling".
Wang 2001e	Second version of Wang 2001d
Wang 2003a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated according to admission order.
Wang 2003b	Described as a 'randomised controlled trial'. We telephone interviewed the original author to identify which method of randomisation was used in the trial. From the author's description, we judged that it actually was a non‐RCT.
Wang 2004b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and he answered "allocated according to the admission order but not exactly".
Wang 2004c	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by the authors optionally.
Wang 2004d	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated according to admission order and age.
Wang 2007a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by the author optionally.
Wang 2007b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned about that the patients were allocated optionally.
Wang 2007c	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated according to the order they came to hospital.
Wang 2007d	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the doctor optionally.
Wang 2007e	Described as a 'randomised controlled trial'. The original author acknowledged that it was a retrospective paper.
Wang 2008b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated according to the admission order.
Wu 1999	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the authors optionally.
Wu 2000a	Described as a 'randomised controlled trial'. We telephone interviewed the original author to identify which method of randomisation was used in the trial. From the author's description, we judged it actually was a non‐RCT.
Wu 2000b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and confirmed that it was a retrospective paper.
Wu 2002c	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the authors were allocated by the authors optionally.
Wu 2003	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the authors optionally.
Wu 2004a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that it was a retrospective paper.
Wu 2004b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the authors optionally.
Wu 2007	Described as a 'randomised controlled trial'. We telephone interviewed the original author and he refused the interview.
Xiao 1997	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated according to admission order without any randomisation method.
Xiao 1999	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated according to admission order without any randomisation method.
Xiao 2002	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that no randomisation method was used to allocate patients.
Xie 1994	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the allocation method was described as "random sampling".
Xie 1995	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the authors optionally.
Xie 2003	Described as a 'randomised controlled trial'. The original author refused our telephone interview.
Xie 2008	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by the author optionally.
Xin 2007	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by doctor optionally.
Xing 2003	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the allocation method was described as "randomly sampled".
Xiong 2007	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the allocation was performed optionally.
Xu 1996	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the allocation method was described as "random sampling and found some patients as control".
Xu 2001	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the authors optionally.
Xu 2002	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that it was a retrospective paper.
Xu 2004	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the allocation method was described as "according to admission order but not exactly".
Xu 2007	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the allocation of patients was performed optionally.
Xue 2000a	Described as a 'randomised controlled trial'. The original author refused our telephone interview.
Xue 2000b	The second version of Xue 2000a
Xue 2001	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the authors optionally.
Yan 2002	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the allocation method was stated as "random sampling".
Yan 2007a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned the patients were allocated according to order of admission.
Yan 2007b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients had actually been allocated optionally.
Yan 2007c	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned about that the patients were allocated optionally.
Yang 1999b	Described as a 'randomised controlled trial'. The original author refused our telephone interview.
Yang 2000a	The cause of "upper respiratory tract infection" was influenza, not common cold
Yang 2001	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated according to admission order without any randomisation.
Yang 2002	The second version of Yang 2001
Yang 2004	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by the author optionally.
Yang 2005	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the authors optionally.
Yang 2007a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that this was a retrospective study about the author's clinical experience.
Yang 2007b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that allocation was by admission order.
Yang 2007c	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned about that the patients were allocated optionally.
Yang 2007d	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the doctor optionally.
Yang 2007e	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that allocation was according to date of admission.
Yao 2001	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the authors optionally.
Yao 2003a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that no randomisation method was used in the trial; the patients in the control group were "random sampling" from outpatients.
Yao 2003b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the author optionally.
Yao 2005	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the authors optionally.
Ye 2000	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that it was a retrospective paper.
Ye 2004	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the author optionally.
Ye 2005a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the authors optionally.
Ye 2005b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated according to admission order without any randomisation.
Yi 1999a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the author optionally.
Yin 2005	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by the authors optionally.
Yin 2007	Described as a 'randomised controlled trial'. We telephoned the original author and learned that the patients were allocated according to the order patients came to hospital.
Yu 1998	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the authors optionally.
Yu 2001a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that it was a retrospective paper.
Yu 2001b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the authors optionally.
Yu 2002	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the authors optionally.
Yu 2004b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the authors optionally.
Yu 2004c	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned this was a retrospective study.
Yu 2007a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by the author optionally.
Yuan 1998	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the author optionally.
Zhai 2004	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the authors optionally.
Zhang 1999a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the authors optionally.
Zhang 2000a	Randomised controlled trial, but the included participants had promyelocytic leukaemia combined with the common cold
Zhang 2000d	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated according to admission order without any randomisation.
Zhang 2001	The author told us that this study design was "not according to current RCT standard"
Zhang 2001b	Described as a 'randomised controlled trial'. We telephone interviewed the original author to learn the randomisation method. It was described as simple randomisation (lot) and as "matched" allocation, but the 2 arms were not balanced (30/20); we thus judged that it was not a RCT.
Zhang 2001c	The second version of Zhang 2001b
Zhang 2001d	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the author optionally.
Zhang 2001e	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the author optionally.
Zhang 2002c	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that this was a retrospective paper.
Zhang 2002d	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the author optionally.
Zhang 2003a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that it was a retrospective study.
Zhang 2003b	Described as a 'randomised controlled trial'. The original author refused our telephone interview.
Zhang 2003c	Data unusable
Zhang 2003e	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the author optionally.
Zhang 2004a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the author optionally.
Zhang 2007a	Described as a 'randomised controlled trial'. The original author refused our telephone interview.
Zhang 2007b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the doctor optionally.
Zhang 2007c	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the allocation of patients was performed optionally.
Zhao 1998a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that it was a retrospective study.
Zhao 1998b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the author optionally.
Zhao 1999	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the author optionally.
Zhao 2000	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the author optionally.
Zhao 2001a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that it was a retrospective study.
Zhao 2002a	Although the study was identified as real a RCT by telephone interview, some patients with fever were given acetanilide and those patients were not reported, therefore the results were confounded.
Zhao 2002b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated by the author optionally.
Zhao 2003	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated according to admission date without any randomisation.
Zhao 2004	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that it was a retrospective study.
Zhao 2007	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned about that the patients were allocated optionally.
Zheng 2003a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that it was a retrospective study.
Zheng 2003b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the allocation method was described as according to admission date without any randomisation.
Zhou 1998a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the patients were allocated according to admission number without any randomisation.
Zhou 1998b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the allocation method was described as "according to admission number but not exactly".
Zhou 2000	Described as a 'randomised controlled trial'. We telephone interviewed the original author and the allocation method was described as "according to admission order but not exactly".
Zhu 1997	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that it was a retrospective study.
Zhu 1998	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that it was a retrospective study.
Zhu 2000c	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by the authors optionally.
Zhu 2002b	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that it was an observational study.
Zhu 2004a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the authors optionally.
Zhuang 2004	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that the children were allocated by the author optionally.
Zou 1997a	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by the authors.
Zou 2008	Described as a 'randomised controlled trial'. We telephone interviewed the original author and learned that patients were allocated by the author optionally.

RCT = randomised controlled trial

Characteristics of studies awaiting assessment [ordered by study ID]

Cai 2001.

Methods
Participants
Interventions
Outcomes
Notes

Chen 1998.

Methods
Participants
Interventions
Outcomes
Notes

Chen 2000a.

Methods
Participants
Interventions
Outcomes
Notes

Chen 2000b.

Methods
Participants
Interventions
Outcomes
Notes

Chen 2001a.

Methods
Participants
Interventions
Outcomes
Notes

Chen 2002.

Methods
Participants
Interventions
Outcomes
Notes

Ding 2004.

Methods
Participants
Interventions
Outcomes
Notes

Ding 2007.

Methods
Participants
Interventions
Outcomes
Notes

Dong 2004.

Methods
Participants
Interventions
Outcomes
Notes

Fang 2008.

Methods
Participants
Interventions
Outcomes
Notes

Feng 1997.

Methods
Participants
Interventions
Outcomes
Notes

Feng 2008.

Methods
Participants
Interventions
Outcomes
Notes

Gu 2004.

Methods
Participants
Interventions
Outcomes
Notes

Gu 2005a.

Methods
Participants
Interventions
Outcomes
Notes

Guo 1996.

Methods
Participants
Interventions
Outcomes
Notes

Guo 2000b.

Methods
Participants
Interventions
Outcomes
Notes

Han 2003.

Methods
Participants
Interventions
Outcomes
Notes

Han 2003b.

Methods
Participants
Interventions
Outcomes
Notes

Hao 2004.

Methods
Participants
Interventions
Outcomes
Notes

He 2001.

Methods
Participants
Interventions
Outcomes
Notes

Hou 1998.

Methods
Participants
Interventions
Outcomes
Notes

Hu 1997.

Methods
Participants
Interventions
Outcomes
Notes

Hu 2007a.

Methods
Participants
Interventions
Outcomes
Notes

Huang 1997.

Methods
Participants
Interventions
Outcomes
Notes

Huang 2000.

Methods
Participants
Interventions
Outcomes
Notes

Huang 2002.

Methods
Participants
Interventions
Outcomes
Notes

Jiang 1996.

Methods
Participants
Interventions
Outcomes
Notes

Jiang 2003b.

Methods
Participants
Interventions
Outcomes
Notes

Jiang 2008.

Methods
Participants
Interventions
Outcomes
Notes

Li 2000b.

Methods
Participants
Interventions
Outcomes
Notes

Li 2001.

Methods
Participants
Interventions
Outcomes
Notes

Li 2002a.

Methods
Participants
Interventions
Outcomes
Notes

Li 2002b.

Methods
Participants
Interventions
Outcomes
Notes

Li 2002d.

Methods
Participants
Interventions
Outcomes
Notes

Li 2002e.

Methods
Participants
Interventions
Outcomes
Notes

Li 2004b.

Methods
Participants
Interventions
Outcomes
Notes

Li 2004c.

Methods
Participants
Interventions
Outcomes
Notes

Li 2004d.

Methods
Participants
Interventions
Outcomes
Notes

Liang 2000.

Methods
Participants
Interventions
Outcomes
Notes

Lin 1999b.

Methods
Participants
Interventions
Outcomes
Notes

Lin 2001.

Methods
Participants
Interventions
Outcomes
Notes

Ling 1998.

Methods
Participants
Interventions
Outcomes
Notes

Liu 2001a.

Methods
Participants
Interventions
Outcomes
Notes

Liu 2007.

Methods
Participants
Interventions
Outcomes
Notes

Liu 2008b.

Methods
Participants
Interventions
Outcomes
Notes

Luo 2003.

Methods
Participants
Interventions
Outcomes
Notes

Luo 2007.

Methods
Participants
Interventions
Outcomes
Notes

Lv 2001.

Methods
Participants
Interventions
Outcomes
Notes

Ma 2000a.

Methods
Participants
Interventions
Outcomes
Notes

Ma 2000c.

Methods
Participants
Interventions
Outcomes
Notes	Waiting for identify the method of randomisation used.

Mei 2003.

Methods
Participants
Interventions
Outcomes
Notes

Meng 2000.

Methods
Participants
Interventions
Outcomes
Notes

Meng 2003a.

Methods
Participants
Interventions
Outcomes
Notes

Meng 2003b.

Methods
Participants
Interventions
Outcomes
Notes

Miao 2000.

Methods
Participants
Interventions
Outcomes
Notes

Miao 2002.

Methods
Participants
Interventions
Outcomes
Notes

Nie 2000.

Methods
Participants
Interventions
Outcomes
Notes

Niu 2003.

Methods
Participants
Interventions
Outcomes
Notes

Ren 2003.

Methods
Participants
Interventions
Outcomes
Notes

Rong 1999.

Methods
Participants
Interventions
Outcomes
Notes

Sheng 2001.

Methods
Participants
Interventions
Outcomes
Notes

Shi 1998a.

Methods
Participants
Interventions
Outcomes
Notes

Su 1994.

Methods
Participants
Interventions
Outcomes
Notes

Sun 1999a.

Methods
Participants
Interventions
Outcomes
Notes

Tao 1996.

Methods
Participants
Interventions
Outcomes
Notes

Tao 2001.

Methods
Participants
Interventions
Outcomes
Notes

Wang 1995c.

Methods
Participants
Interventions
Outcomes
Notes

Wang 2008c.

Methods
Participants
Interventions
Outcomes
Notes

Wei 2008.

Methods
Participants
Interventions
Outcomes
Notes

Wu 2002a.

Methods
Participants
Interventions
Outcomes
Notes

Wu 2002b.

Methods
Participants
Interventions
Outcomes
Notes

Wu 2003c.

Methods
Participants
Interventions
Outcomes
Notes

Xu 1999a.

Methods
Participants
Interventions
Outcomes
Notes

Xu 1999b.

Methods
Participants
Interventions
Outcomes
Notes

Yan 2000.

Methods
Participants
Interventions
Outcomes
Notes

Yang 1999a.

Methods
Participants
Interventions
Outcomes
Notes

Yu 2003.

Methods
Participants
Interventions
Outcomes
Notes

Yu 2004a.

Methods
Participants
Interventions
Outcomes
Notes

Yu 2007b.

Methods
Participants
Interventions
Outcomes
Notes

Yuan 1999.

Methods
Participants
Interventions
Outcomes
Notes

Zeng 2005.

Methods
Participants
Interventions
Outcomes
Notes

Zhang 1997.

Methods
Participants
Interventions
Outcomes
Notes

Zhang 1999b.

Methods
Participants
Interventions
Outcomes
Notes

Zhang 2000b.

Methods
Participants
Interventions
Outcomes
Notes

Zhang 2000c.

Methods
Participants
Interventions
Outcomes
Notes

Zhang 2002a.

Methods
Participants
Interventions
Outcomes
Notes

Zhang 2002b.

Methods
Participants
Interventions
Outcomes
Notes

Zhang 2002e.

Methods
Participants
Interventions
Outcomes
Notes

Zhang 2003d.

Methods
Participants
Interventions
Outcomes
Notes

Zhang 2004b.

Methods
Participants
Interventions
Outcomes
Notes

Zhang 2004c.

Methods
Participants
Interventions
Outcomes
Notes

Zhang 2004d.

Methods
Participants
Interventions
Outcomes
Notes

Zhang 2004e.

Methods
Participants
Interventions
Outcomes
Notes

Zhao 2001b.

Methods
Participants
Interventions
Outcomes
Notes

Zheng 1996.

Methods
Participants
Interventions
Outcomes
Notes

Zheng 1998.

Methods
Participants
Interventions
Outcomes
Notes

Zheng 2001.

Methods
Participants
Interventions
Outcomes
Notes

Zhong 2002.

Methods
Participants
Interventions
Outcomes
Notes

Zhou 1999a.

Methods
Participants
Interventions
Outcomes
Notes

Zhou 1999b.

Methods
Participants
Interventions
Outcomes
Notes

Zhou 2003.

Methods
Participants
Interventions
Outcomes
Notes

Zhou 2004a.

Methods
Participants
Interventions
Outcomes
Notes

Zhou 2004c.

Methods
Participants
Interventions
Outcomes
Notes

Zhu 2000a.

Methods
Participants
Interventions
Outcomes
Notes

Zhu 2000b.

Methods
Participants
Interventions
Outcomes
Notes

Zhu 2002a.

Methods
Participants
Interventions
Outcomes
Notes

Zhu 2004b.

Methods
Participants
Interventions
Outcomes
Notes

Zou 1997b.

Methods
Participants
Interventions
Outcomes
Notes

Zuo 2008.

Methods
Participants
Interventions
Outcomes
Notes

Differences between protocol and review

1. We have modified the 'Quality assessment of included studies' in the original version to 'Assessment of risk of bias in included studies' according to the new version of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2008).

2. We have modified the ongoing trials search strategy.

Contributions of authors

Taixiang Wu (WT) organised the review team, extracted data, assessed trial quality and wrote the review. 
 Xiaoge Zhang (ZX) updated this version of review and telephone interviewed the trial authors. 
 Jing Zhang(ZJ), Yan Qiu (QY) and Lingxia Xie (XLX) interviewed trial authors by telephone for the original version of review. 
 Guanjian Liu (LG) analysed the data.

Sources of support

Internal sources

• Chinese Cochrane Center, Chinese Centre of Evidence‐Based Medicine, West China Hospital of Sichuan University, China.

External sources

• China Medical Board of New York, USA.

Declarations of interest

None known.

Edited (no change to conclusions)