Abstract
Background:
Ethical conduct of research depends on the voluntary expression of consent and adequate disclosure of information about the research in informed consent documents (ICDs).
Objectives:
The objective of this study was to analyze ICDs of academic studies for compliance with National Ethical Guidelines for Biomedical and Health Research laid down by the Indian Council of Medical Research (ICMR) and to determine the readability of ICDs using the Flesch–Kincaid Grade Level scale and Flesch reading-ease (FRE) score.
Methodology:
ICDs of academic research projects submitted during 2020–22 were retrieved from the IEC office and analyzed for compliance with ICMR 2017 guidelines. The readability of the documents was assessed by the Flesch–Kincaid Grade Level Scale and FRE score.
Results:
Among 177 protocols analyzed, the most common were epidemiological studies (36.72%), followed by diagnostic studies (28.81%). Vernacular translations of ICDs were present in significantly more studies in 2022 (χ2 = 7.18, P = 0.02) as compared to 2020 and 2021. FREs score was 45.75 ± 10.76, and Flesch–Kincaid Grade Level was 8.67 ± 1.44. Content analysis of participant information sheet (PIS) revealed that significantly more PIS submitted in 2022 mentioned expected duration of participation (χ2 = 6.95, P < 0.001), benefit to patient/community (χ2 = 26.63, P < 0.001), disclosure of foreseeable risk or discomfort (χ2 = 21.72, P < 0.001), payment for participation (χ2 = 21.72, P < 0.001), and identity of research team and contact details (χ2 = 18.58, P < 0.001). Compliance score was significantly better in 2022 as compared to 2020 and 2021.
Conclusion:
Gradually, ICDs became more compliant with ICMR guidelines. Still, there is scope for improvement in ICDs regarding content and readability so that patients can comprehend facts easily to make informed decisions in a real sense.
Keywords: Indian Council of Medical Research guidelines, informed consent document, patient information sheet
INTRODUCTION
Biomedical and health research contributes significantly to the generation of evidence that eventually dictates policy. Scientifically sound research questions, robust research methodology, and rigorous ethical and scientific governance are prerequisites.[1] Every research has some inherent risk and possibility of harm or inconvenience to participants or communities. Hence, research involving human participants must be preemptively accepted by the participants themselves. Informed consent documents (ICDs) are one, albeit critical, element in a research process. The informed consent procedure can facilitate a shared decision-based health-care plan, which is crucially dependent on the voluntary expression of consent and adequate disclosure of information about the research.[2] Unethical practices adopted during the PATH trial for the Human papillomavirus (HPV) vaccine in Trible Girls of Madhya Pradesh, India, highlighted the issue of the informed consent process.[3]
Current guidelines by the Indian Council of Medical Research (ICMR) clearly mention essential and additional elements to be present in ICDs for biomedical and health research involving human participants.[4] However, translation of these ethical requirements into actual practice poses many challenges, especially for academic research due to limited resources, feasibility, time, and staff constraints.[5] Study participants still remain inadequately informed despite the strict guidelines due to a lack of essential information in ICDs which could be because of ignorance of investigators regarding essential elements. Often, patients are also reluctant to know more about the study, potential risk, expected benefits, consequences, their rights due to an implicit trust in the medical system, and treating doctors and ignorance about the information that should be known before consenting to be a part of the research study. In addition, socioeconomic issues such as language barriers, religious influences, and literacy levels prevent participants from accurately understanding the study.[6,7,8] In addition to content, another important factor that needs to be considered is the readability and comprehensibility of documents. It must be written in language easily understood by the subjects. The acceptable language in ICDs should be preferably equivalent to that of the local middle school level of education and essentially nontechnical to suit the solicited community.[9]
Various studies evaluated compliance of ICDs for sponsored clinical trials which reported lack of key information such as availability of alternatives, participant’s rights, and publication policy.[10,11] Studies observed that ICDs for sponsored clinical trials were too long, difficult to read, and exceeded Grade 9 in language complexity.[2] In this context, it might be assumed that present informed consent practices fall short of the ethical requirement of autonomy.
We conducted a thorough literature search but were unable to locate information on academic studies’ ICDs’ conformity with the most recent ICMR standards. It will be intriguing yet crucial to know how many academic studies adhere to ICMR guidelines for preparing ICDs and their ease of readability. Hence, we decided to analyze ICDs of academic proposals for content and readability.
Objectives
To analyze ICDs of academic studies submitted to the Institutional Ethics Committee (IEC) and to determine their compliance with National Ethical Guidelines for Biomedical and Health Research laid down by ICMR
To assess the change in compliance pattern over the time period from 2020 to 2022
To calculate the readability of ICDs using Flesch–Kincaid Grade Level Scale and Flesch reading ease (FRE) score.
METHODOLOGY
In the present retrospective analytical study, ICDs comprising participant information sheets (PIS) and consent forms accompanying research protocols submitted to the single IEC of the Institute of National Importance from 2020 to 2022 were evaluated after taking administrative approval for accessing the documents from the concerned authorities. Confidentiality of the documents was maintained throughout the study period. The study was approved by Research Cell and IEC (IEC/Pharmac/2022/460 Date August 22, 2022) and was carried out in accordance with Good Clinical Practice (GCP) guidelines and the ethical principles as mentioned in the declaration of Helsinki and ICMR guidelines.
ICDs of all academic research projects including prospective interventional/observational studies for evaluation of drugs, therapy, medical devices, new techniques, diagnostic measures/techniques, epidemiological, or other studies involving human participation submitted to IEC for initial review were retrieved and analyzed. ICDs of sponsored clinical trials and protocols based on analysis of anonymized data/sample and cadaveric studies were excluded from the analysis. Unique identity number was allotted to each protocol and true identity parameters were not revealed during data entry and analysis. The patient information sheets were scrutinized for the inclusion of 14 essential/additional information elements outlined in ICMR 2017 guidelines. ICDs were categorized year-wise (2020, 2021, and 2022), funding status, and type of study design and analyzed to observe changes in compliance patterns regarding ICDs’ content.
Study instrument
National ethical guidelines for biomedical and health research involving human participants formulated by ICMR 2017[12] had provided list of essential and additional elements to be provided in ICDs. This checklist was used as a reference standard which is also in conformity with those mentioned in other international standards such as the US Code of Federal Regulation (21CFR50.25).[13]
The information in each PIS is coded as “essential/additional elements present” scored as + 1 or “essential/additional elements absent” scored as 0. The scoring system is referred from previous study.[10] A score in the range of 0–14 was possible for an individual ICD. Compliance score was calculated for each PIS.
Calculation of readability score
The readability of the documents was assessed by the Flesch–Kincaid Grade Level Scale and FRE score which were calculated using formula based on total words, total sentences, and total syllables in the document. The FRE gives a document a score between 1 and 100, with 100 being the highest readability score means the document is fairly easy for the average adult to read.[14,15]
FRE score = 206.835-1.015 (Total words/Total sentences) – 84.6 (Total syllables/Total words.
The Flesch–Kincaid Grade Level is a widely used readability formula that assesses a document’s approximate reading grade level. If a document has a Flesch–Kincaid level of 8, it means the reader needs a Grade 8 level of reading or above to understand it.
Flesch–Kincaid Grade Level = 0.39 (Total words/Total sentences) +11.8 (Total syllables/Total words) – 15.59.
Statistical analysis
The data were expressed in numbers and percentages or as mean ± standard deviation (SD) wherever applicable. Kruskal–Wallis test was used to compare readability scores and compliance scores over 3 years. Chi-square test was used to test whether there is a significant difference in the content of PIS submitted in 2021 and 2022 as compared to PIS submitted in 2020. For post hoc analysis, adjusted residuals were calculated. We computed the Chi-square value and P value taking into consideration adjusted residuals. Bonferroni corrected/adjusted P value was calculated by multiplying the observed (uncorrected) P value by the number of comparisons made. P <0.05 was considered statistically significant. IBM SPSS Statistics for Windows, version 25.0. Armonk, NY, USA: IBM Corp was used for analysis.
RESULTS
Among 237 protocols submitted to the IEC between January 2020 and December 2022, 177 protocols were included in the analysis. Sixty protocols were excluded due to reasons such as anonymized sample/data analysis (31), cadaveric study (3), and retrospective data analysis (26).
Studies were categorized according to study type, as shown in Table 1. The most common were epidemiological studies (36.72%) and diagnostic studies (28.81%). Among the proposals submitted, 31 (17.51%) studies were funded by either institute or government funding agencies. Vernacular translation of ICD was present in 148 studies. Vernacular translations of ICDs were present in significantly greater number of studies in 2022 (χ2 = 7.18, P = 0.02) as compared to 2020 and 2021. However, no significant difference was observed in Flesch–Kincaid Grade Level score (H[2] =0.199, P = 0.905) and FRE score (H[2] =0.111, P = 0.94) over a duration of 3 years after analyzing data by Kruskal–Wallis test [Table 1]. None of the study protocols include back translation and translation/back translation certification.
Table 1.
Profile of informed consent documents submitted for institutional ethics committee review (n=177)
| Parameter | 2020 (n=67) | 2021 (n=47) | 2022 (n=63) | Total (n=177) |
|---|---|---|---|---|
| Type of study | ||||
| Drug study | 5 (7.46) | 3 (6.38) | 7 (11.11) | 15 (8.47) |
| Device study | 3 (4.47) | 1 (2.12) | 0 | 4 (2.25) |
| New surgical/medical technique | 1 (1.49) | 3 (6.38) | 7 (11.11) | 11 (6.21) |
| Diagnostic study | 20 (29.85) | 17 (36.17) | 14 (22.22) | 51 (28.81) |
| Epidemiological study | 21 (31.34) | 14 (29.78) | 30 (47.61) | 65 (36.72) |
| Behavioral studies | 17 (25.37) | 9 (19.14) | 5 (7.93) | 31 (17.51) |
| Vernacular translation | 50 (74.62) | 39 (82.97) | 59 (93.65)* | 148 (83.61) |
| Source of funding | ||||
| Self-funding | 60 (89.55) | 37 (78.72) | 49 (77.77) | 146 (82.48) |
| Funded | 7 (10.44) | 10 (21.27) | 14 (22.22) | 31 (17.51) |
| Readability score (mean±SD) | ||||
| Flesch–Kincaid Grade Level | 8.69±1.52 | 8.72±1.38 | 8.62±1.42 | 8.67±1.44 |
| Flesch reading ease score | 45.64±10.68 | 45.27±10.69 | 46.23±11.05 | 45.75±10.76 |
*P<0.05 when compared to year 2020 using Chi-square test followed by Bonferroni correction for adjusted “P” value. Figures in bracket indicates percentage. SD=Standard deviation
Table 2 describes information elements provided in PIS in accordance with ICMR 2017 guidelines. Expected duration of participation was mentioned in 84 PIS. As compared to PIS submitted in 2020, significantly more PIS submitted in 2022 mentioned expected duration of participation (χ2 = 6.95, P < 0.001), benefit to patient/community (χ2 = 26.63, P < 0.001), disclosure of foreseeable risk or discomfort (χ2 = 21.72, P < 0.001), payment for participation (χ2 = 21.72, P < 0.001), identity of research team, and contact details (χ2 = 18.58, P < 0.001). Number of PIS, in which mention of alternative procedure were applicable include 37.8% (2020), 44.68% (2021), and 33.33% (2022). Mention of insurance coverage was applicable for 35.82% (2020), 38.29% (2021), and 26.98% (2022) of PIS. Provision of pretest and posttest counseling was applicable to 35.82% (2020), 21.27% (2021), and 20.63% (2022) of PIS for stigmatizing conditions such as HIV, tuberculosis, leprosy, and COVID-19. Surprisingly, none of the PIS mentioned alternative procedures or courses of treatment, insurance coverage for research-related or other adverse events, and provision of pretest and posttest counseling in case of stigmatizing conditions in research proposals.
Table 2.
Information elements provided in patient information sheet in accordance with Indian Council of Medical Research 2017 guidelines (n=177)
| Information elements in PIS | Year | Information mentioned in PIS, n (%) | Adjusted residual (z-score) | χ 2 | Adjusted P* |
|---|---|---|---|---|---|
| Statement mentioning that it is research | 2020 | 55 (82.08) | |||
| 2021 | 35 (74.46) | −1.69 | 2.86 | 0.27 | |
| 2022 | 56 (88.88) | 1.67 | 2.79 | 0.28 | |
| Purpose and method of research | 2020 | 65 (97.07) | |||
| 2021 | 45 (95.74) | −0.29 | 0.08 | 2.32 | |
| 2022 | 63 (100) | 1.30 | 1.69 | 0.58 | |
| Expected duration of participation | 2020 | 18 (26.86) | |||
| 2021 | 14 (29.78) | −2.83 | 8.01 | 0.83 | |
| 2022 | 52 (82.53) | 6.95 | 48.3 | <0.001 | |
| Benefit to patient/community that might be expected as an outcome of research | 2020 | 32 (47.76) | |||
| 2021 | 35 (74.46) | 0.48 | 0.23 | 1.89 | |
| 2022 | 60 (95.23) | 5.16 | 26.63 | <0.001 | |
| Any foreseeable risk or discomfort to the subject resulting from participation | 2020 | 44 (65.67) | |||
| 2021 | 23 (48.93) | −3.81 | 14.52 | <0.001 | |
| 2022 | 58 (92.06) | 4.66 | 21.72 | <0.001 | |
| The extent to which confidentiality of records could be safeguarded | 2020 | 59 (88.05) | |||
| 2021 | 45 (95.74) | 0.65 | 0.42 | 1.55 | |
| 2022 | 62 (98.41) | 1.90 | 3.61 | 0.17 | |
| Payment for participation and incidental expenses | 2020 | 17 (25.37) | |||
| 2021 | 21 (44.68) | −0.26 | 0.07 | 2.38 | |
| 2022 | 44 (69.84) | 4.66 | 21.72 | <0.001 | |
| Free treatment for research-related injury by the investigator/institution | 2020 | 2 (2.99) | |||
| 2021 | 6 (12.77) | −0.78 | 0.61 | 1.31 | |
| 2022 | 21 (33.33) | 4.53 | 20.52 | <0.001 | |
| Freedom of individual/family to participate and to withdraw from research any time without penalty or loss of benefits | 2020 | 60 (89.55) | |||
| 2021 | 38 (80.85) | −2.38 | 5.66 | 0.05 | |
| 2022 | 61 (96.82) | 2.29 | 5.24 | 0.07 | |
| The identity of the research teams and contact persons with address and phone numbers | 2020 | 41 (61.19) | |||
| 2021 | 35 (74.46) | −0.45 | 0.2 | 1.96 | |
| 2022 | 60 (95.23) | 4.31 | 18.58 | <0.001 | |
| Foreseeable extent of information on possible current and future use of the biological material or of the data to be generated from research | 2020 | 32 (47.76) | |||
| 2021 | 26 (55.32) | −0.56 | 0.31 | 1.73 | |
| 2022 | 46 (73.02) | 2.86 | 8.18 | <0.001 |
*Using Chi-square test followed by Bonferroni correction for adjusted “P” value when compared to year 2020. PIS=Participant information sheet
Subgroup analysis depending on the status of funding showed that ICDs of funded projects had significantly better compliance scores as compared to self-funded research studies (8.25 ± 1.59 vs. 7.41 ± 2.11; P = 0.03). However, there was no significant difference among research proposals funded by different funding agencies such as institutional funding, government agencies, or private funding agencies. Interventional studies had better compliance scores as compared to observational studies (8.33 ± 2.21 vs. 7.4 ± 1.99; P = 0.02) [Table 3].
Table 3.
Comparative evaluation of compliance score of participant information sheet among subgroups of research protocols (n=177)
| Parameter | Study type | n (%) | Compliance score | P |
|---|---|---|---|---|
| Status of funding | Received funds from institute/funding agencies | 31 (17.51) | 8.25±1.59* | 0.03 |
| Nonfunded | 146 (82.48) | 7.41±2.11 | ||
| Study design | Interventional | 29 (16.38) | 8.33±2.21* | 0.02 |
| Observational | 148 (83.61) | 7.4±1.99 |
*P<0.05 when compared using Mann–Whitney U-test
Mean (SD) compliance score of PIS was 6.32 ± 1.63 (2020), 6.91 ± 1.82 (2021), and 9.34 ± 1.22 (2022). A Kruskal–Wallis H-test showed that there was a statistically significant difference in the compliance score of PIS (H[2] =82.65, P < 0.001). Post hoc analysis showed that the compliance score was significantly improved in 2022 as compared to 2020 (H[2] =77.66, P < 0.001) and 2021 (H[2] =61.868, P < 0.001) [Figure 1].
Figure 1.
Compliance score for participant information sheet submitted for the duration of 2020–2022. *P < 0.05 when compared using Kruskal–Wallis H-test. PIS = Participant information sheet
DISCUSSION
Informed consent is one of the key elements for protecting participant’s autonomy in clinical research. Within its ethical and legal foundations, the informed consent process is pivotal in supporting ethically sound medical intervention. The goal of the informed consent process is to provide sufficient information to potential participants in a language which is easily understood by them so that they can make voluntary decisions regarding participation in the study.
In the present study, 177 ICDs were analyzed for their information elements. The majority of studies were epidemiological, followed by diagnostic studies.
The present study observed that in 2022, a significantly higher number of ICDs were translated into vernacular language as compared to previous years which is in accordance with previous studies.[10] In a country like India, where the literacy rate is still low, vernacular translation of ICDs is essential. However, none of the study protocols included back translation of PIS and translation/back translation certificate. This issue needs to be highlighted during the training program so that academic researchers will take cognizance. Alternatively, the institute may hire the services of linguistic expert to make it convenient to investigators and finally to the participants.
Analysis of the readability of the ICDs revealed that the reading grade level was within recommended standards but ease of reading scores was less than the recommended standards. The use of technical or scientific words and lengthy sentences might be responsible for low score. However, there was no significant change in the readability of the documents over the period of consideration. FRE readability tests chosen have been widely used in a variety of previous studies.[10,16] Emanuel and Boyle[2] analyzed ICDs of COVID-19 vaccine trials and found that the language complexity in all the documents exceeded a Grade 9 reading level, which is higher than the recommended reading level. In addition, all the documents had scores of < 60 in the reading ease metric.
The acceptable language in ICDs is to be equivalent to that of the local middle school level of education and essentially nontechnical to suit the solicited community.[17] A simple mechanism of reducing the reading difficulty level is by replacing, wherever possible, technical terms with common terms. Using tools such as outlining, bullet points, a large typeface, and diagrams can help the reader to follow complex concepts. Using active verbs rather than the passive voice, short sentences and frequent paragraphing can make text simpler to improve the readability of the document.[9]
After performing content analysis of PIS, we observed that a significant number of sheets had stated about the expected duration of participation which is helpful to patients to get an idea about the treatment plan. Significant number of study proposals submitted in 2022 provided information regarding payment for participation and incidental expenses. It is a welcoming sign to observe that significant number of study proposals mention the benefit to participants/community that might be expected as an outcome of research. In addition, there was a highly significant increase in the number of sheets which provided the contact details of the investigator and the study staff in 2022. A similar trend was observed in previous study by Padhy et al.[10] Study participants may seek additional information about the trial or may need to contact the physician/research staff in an emergency and the provision of contact address or numbers are very useful.
Very few studies mention about free treatment of research-related injury by investigator/institution. Due to lack of financial support, many of the researchers of academic studies are reluctant to disclose information related to the provision of remuneration for participation or free treatment of research-related injury. Surprisingly, not a single PIS mentioned insurance coverage for research-related adverse events. Insurance is a way of risk management primarily used to include the risk of unforeseen and uncertain loss. Insurance-self or institute; whichever be the arrangement. However, the clause that participants will be given free treatment and compensation in research-related injury is essential. ICMR 2017[12] guidelines have specified the need for the provision of compensation to participants for research-related injuries. Although studies mention that insurance policies existed for sponsored clinical trials,[18] in the case of academic studies which are mostly investigator-initiated, the availability of insurance policies and related information in PIS is remote possibility. In the case of clinical trials, the sponsor decides the amount of insurance coverage and thus the premium to be paid. It is a costly affair. In the case of academic studies, the guideline states that the “host institution” is responsible for providing compensation and should have in-built provisions for this. Research institutions in the country should create a corpus for the provision of free treatment and compensation for research-related injury.[1]
Resnik et al. analyzed the quality of information about alternatives contained in ICDs from Phases II, III, or IV nonpediatric U.S. Oncology randomized controlled trials registered in Clinicaltrials.gov. He concluded that disclosure of alternatives in consent forms is often deficient.[11] A systematic review conducted by Lühnen et al. in Germany for content analysis of informed consent forms observed grave deficiencies in terms of lacking information on benefits, alternatives, and inadequate risk communication.[19]
We admit that it is possible for investigators to provide subjects with all pertinent information during the consent process that is not included in the consent document, but we do not anticipate this to happen frequently because there is so much to cover during the consent process, including the nature of the research and risks and benefits. Furthermore, even though the consent document is only a part of the consent process, it is still crucial to make sure that it contains crucial information that subjects may need to make decisions, as subjects are prone to forgetting information they were given during informal conversations with researchers, over which IRBs have no control.[20] Since most IRBs do not routinely observe the process of consent, the IRB’s primary method for ensuring that subjects receive the information they need to know is to require that the information be included in the consent document.
In our study, significant improvement in the compliance score of the ICDs was observed in 2022 as compared to 2020 and 2021. Improvement in compliance with ICMR guidelines reflects increased awareness among researchers regarding ethical conduct of research and informed decision-making process which might be due to regular training workshops on GCP conducted by IEC. Padhy et al. also reported improvement in compliance after sharing a model ICD format highlighting the essential information to be provided to potential trial participants in accordance with Indian GCP guidelines.[10]
Compliance score of ICDs of funded studies was better as compared to nonfunded studies. Since documents of study protocol need to be submitted to the funding agency, so investigator might be more cautious while preparing the ICD.
The present study analyzed compliance of ICDs with the regulatory requirements and readability from single ethics committee only. We had also not analyzed the quality of information and comprehensibility which assess the patient’s ability to understand the information presented.
CONCLUSION
Gradually, ICDs became more compliant with ICMR guidelines. Financial constraints hinder disclosure of remuneration or free treatment for research-related injury. Recommendations are proposed, including the establishment of financial support, sharing of model ICD templates, and regular training sessions on GCPs that will promote ethical conduct of research. Emphasis should be placed on refining content and improving the readability of ICDs to ensure that participants can easily comprehend information for informed decision-making.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
REFERENCES
- 1.Konwar M, Bose D, Gogtay NJ, Thatte UM. Investigator-initiated studies: Challenges and solutions. Perspect Clin Res. 2018;9:179–83. doi: 10.4103/picr.PICR_106_18. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Emanuel EJ, Boyle CW. Assessment of length and readability of informed consent documents for COVID-19 vaccine trials. JAMA Netw Open. 2021;4:e2110843. doi: 10.1001/jamanetworkopen.2021.10843. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.The HPV Vaccine: Science, Ethics and Regulation; 2010. [[Last accessed on 2023 Jun 26]]. Available from: https://www.epw.in/journal/2010/48/insight/hpv-vaccine-scienceethics-and-regulation.html .
- 4.Mathur R, Swaminathan S. National ethical guidelines for biomedical and health research involving human participants, 2017: A commentary. Indian J Med Res. 2018;148:279–83. doi: 10.4103/0971-5916.245303. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Nijhawan LP, Janodia MD, Muddukrishna BS, Bhat KM, Bairy KL, Udupa N, et al. Informed consent: Issues and challenges. J Adv Pharm Technol Res. 2013;4:134–40. doi: 10.4103/2231-4040.116779. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Loh WY, Butow PN, Brown RF, Boyle F. Ethical communication in clinical trials. Issues faced by data managers in obtaining informed consent. Cancer. 2002;95:2414–21. doi: 10.1002/cncr.10994. [DOI] [PubMed] [Google Scholar]
- 7.Lynöe N, Näsström B, Sandlund M. Study of the quality of information given to patients participating in a clinical trial regarding chronic hemodialysis. Scand J Urol Nephrol. 2004;38:517–20. doi: 10.1080/00365590410033362. [DOI] [PubMed] [Google Scholar]
- 8.Penman DT, Holland JC, Bahna GF, Morrow G, Schmale AH, Derogatis LR, et al. Informed consent for investigational chemotherapy: Patients'and physicians'perceptions. J Clin Oncol. 1984;2:849–55. doi: 10.1200/JCO.1984.2.7.849. [DOI] [PubMed] [Google Scholar]
- 9.Pandiya A. Readability and comprehensibility of informed consent forms for clinical trials. Perspect Clin Res. 2010;1:98–100. [PMC free article] [PubMed] [Google Scholar]
- 10.Padhy BM, Gupta P, Gupta YK. Analysis of the compliance of informed consent documents with good clinical practice guideline. Contemp Clin Trials. 2011;32:662–6. doi: 10.1016/j.cct.2011.05.016. [DOI] [PubMed] [Google Scholar]
- 11.Resnik DB, Patrone D, Peddada S. Evaluating the quality of information about alternatives to research participation in oncology consent forms. Contemp Clin Trials. 2010;31:18–21. doi: 10.1016/j.cct.2009.11.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Indian Council of Medical Research. National Ethical Guidelines for Biomedical and Health Research Involving Human Participants. New Delhi: Indian Council of Medical Research; 2017. [[Last accessed on 2023 Sep 01]]. Available from: https://www.icmr.nic.in/sites/default/files/guidelines/ICMR_Ethical_Guidelines_2017.pdf . [Google Scholar]
- 13.International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. Integrated addendum to ICHE6(R1): Guideline for good clinical practice E6(R2). Current Step 4 version dated 09 November 2016. [[Last accessed on 2023 Sep 01]]. Available from: https://database.ich.org/sites/default/files/E6_R2_Addendum.pdf .
- 14.Flesch R. A new readability yardstick. J Appl Psychol. 1948;32:221–33. doi: 10.1037/h0057532. [DOI] [PubMed] [Google Scholar]
- 15.Kincaid JP, Fishburne RP, Jr, Rogers RL, Chissom BS, Fishburne RP, Jr, Rogers RL, et al. Derivation of New Readability Formulas (Automated Readability Index, Fog Count and Flesch Reading Ease Formula) for Navy Enlisted Personnel (No. RBR-8-75). Naval Technical Training Command Millington TN Research Branch. 1975. [[Last accessed on 2023 Sep 01]]. Available from: https://oai.dtic.mil/oai/oai?verb=getRecordand metadataPrefix=html and identifier=ADA006655 .
- 16.Kher A, Johnson S, Griffith R. Readability assessment of online patient education material on congestive heart failure. Adv Prev Med. 2017;2017:1–8. doi: 10.1155/2017/9780317. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Poongothai S, Unnikrishnan R, Balasubramanian J, Nair MD, Mohan V. Why are clinical trials necessary in India? Perspect Clin Res. 2014;5:55–9. doi: 10.4103/2229-3485.128018. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Kalikar MV, Dakhale GN, Sinha VV, Giradkar AB. Analysis of clinical trial agreement and insurance policy submitted to the ethics committee of a tertiary care teaching institute in central India. Perspect Clin Res. 2022;13:151–4. doi: 10.4103/picr.PICR_124_20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Lühnen J, Mühlhauser I, Steckelberg A. The quality of informed consent forms-a systematic review and critical analysis. Dtsch Arztebl Int. 2018;115:377–83. doi: 10.3238/arztebl.2018.0377. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Resnik DB. Do informed consent documents matter? Contemp Clin Trials. 2009;30:114–5. doi: 10.1016/j.cct.2008.10.004. [DOI] [PMC free article] [PubMed] [Google Scholar]