Interventions for preventing falls in Parkinson's disease

Natalie E Allen; Colleen G Canning; Lorena Rosa S Almeida; Bastiaan R Bloem; Samyra HJ Keus; Niklas Löfgren; Alice Nieuwboer; Geert SAF Verheyden; Tiê P Yamato; Catherine Sherrington

doi:10.1002/14651858.CD011574.pub2

. 2022 Jun 6;2022(6):CD011574. doi: 10.1002/14651858.CD011574.pub2

Interventions for preventing falls in Parkinson's disease

Natalie E Allen ^1,^✉, Colleen G Canning ¹, Lorena Rosa S Almeida ^2,³, Bastiaan R Bloem ⁴, Samyra HJ Keus ^5,⁶, Niklas Löfgren ^1,^7,⁸, Alice Nieuwboer ⁹, Geert SAF Verheyden ⁹, Tiê P Yamato ¹⁰, Catherine Sherrington ¹¹

Editor: Cochrane Movement Disorders Group

PMCID: PMC9169540 PMID: 35665915

Abstract

Background

Most people with Parkinson’s disease (PD) experience at least one fall during the course of their disease. Several interventions designed to reduce falls have been studied. An up‐to‐date synthesis of evidence for interventions to reduce falls in people with PD will assist with informed decisions regarding fall‐prevention interventions for people with PD.

Objectives

To assess the effects of interventions designed to reduce falls in people with PD.

Search methods

CENTRAL, MEDLINE, Embase, four other databases and two trials registers were searched on 16 July 2020, together with reference checking, citation searching and contact with study authors to identify additional studies. We also conducted a top‐up search on 13 October 2021.

Selection criteria

We included randomised controlled trials (RCTs) of interventions that aimed to reduce falls in people with PD and reported the effect on falls. We excluded interventions that aimed to reduce falls due to syncope.

Data collection and analysis

We used standard Cochrane Review procedures. Primary outcomes were rate of falls and number of people who fell at least once. Secondary outcomes were the number of people sustaining one or more fall‐related fractures, quality of life, adverse events and economic outcomes. The certainty of the evidence was assessed using GRADE.

Main results

This review includes 32 studies with 3370 participants randomised. We included 25 studies of exercise interventions (2700 participants), three studies of medication interventions (242 participants), one study of fall‐prevention education (53 participants) and three studies of exercise plus education (375 participants). Overall, participants in the exercise trials and the exercise plus education trials had mild to moderate PD, while participants in the medication trials included those with more advanced disease. All studies had a high or unclear risk of bias in one or more items. Illustrative risks demonstrating the absolute impact of each intervention are presented in the summary of findings tables.

Twelve studies compared exercise (all types) with a control intervention (an intervention not thought to reduce falls, such as usual care or sham exercise) in people with mild to moderate PD. Exercise probably reduces the rate of falls by 26% (rate ratio (RaR) 0.74, 95% confidence interval (CI) 0.63 to 0.87; 1456 participants, 12 studies; moderate‐certainty evidence). Exercise probably slightly reduces the number of people experiencing one or more falls by 10% (risk ratio (RR) 0.90, 95% CI 0.80 to 1.00; 932 participants, 9 studies; moderate‐certainty evidence).

We are uncertain whether exercise makes little or no difference to the number of people experiencing one or more fall‐related fractures (RR 0.57, 95% CI 0.28 to 1.17; 989 participants, 5 studies; very low‐certainty evidence). Exercise may slightly improve health‐related quality of life immediately following the intervention (standardised mean difference (SMD) ‐0.17, 95% CI ‐0.36 to 0.01; 951 participants, 5 studies; low‐certainty evidence). We are uncertain whether exercise has an effect on adverse events or whether exercise is a cost‐effective intervention for fall prevention.

Three studies trialled a cholinesterase inhibitor (rivastigmine or donepezil). Cholinesterase inhibitors may reduce the rate of falls by 50% (RaR 0.50, 95% CI 0.44 to 0.58; 229 participants, 3 studies; low‐certainty evidence). However, we are uncertain if this medication makes little or no difference to the number of people experiencing one or more falls (RR 1.01, 95% CI 0.90 to 1.14; 230 participants, 3 studies) and to health‐related quality of life (EQ5D Thermometer mean difference (MD) 3.00, 95% CI ‐3.06 to 9.06; very low‐certainty evidence). Cholinesterase inhibitors may increase the rate of non fall‐related adverse events by 60% (RaR 1.60, 95% CI 1.28 to 2.01; 175 participants, 2 studies; low‐certainty evidence). Most adverse events were mild and transient in nature. No data was available regarding the cost‐effectiveness of medication for fall prevention.

We are uncertain of the effect of education compared to a control intervention on the number of people who fell at least once (RR 10.89, 95% CI 1.26 to 94.03; 53 participants, 1 study; very low‐certainty evidence), and no data were available for the other outcomes of interest for this comparisonWe are also uncertain (very low‐certainty evidence) whether exercise combined with education makes little or no difference to the number of falls (RaR 0.46, 95% CI 0.12 to 1.85; 320 participants, 2 studies), the number of people sustaining fall‐related fractures (RR 1.45, 95% CI 0.40 to 5.32,320 participants, 2 studies), or health‐related quality of life (PDQ39 MD 0.05, 95% CI ‐3.12 to 3.23, 305 participants, 2 studies). Exercise plus education may make little or no difference to the number of people experiencing one or more falls (RR 0.89, 95% CI 0.75 to 1.07; 352 participants, 3 studies; low‐certainty evidence). We are uncertain whether exercise combined with education has an effect on adverse events or is a cost‐effective intervention for fall prevention.

Authors' conclusions

Exercise interventions probably reduce the rate of falls, and probably slightly reduce the number of people falling in people with mild to moderate PD.

Cholinesterase inhibitors may reduce the rate of falls, but we are uncertain if they have an effect on the number of people falling. The decision to use these medications needs to be balanced against the risk of non fall‐related adverse events, though these adverse events were predominantly mild or transient in nature.

Further research in the form of large, high‐quality RCTs are required to determine the relative impact of different types of exercise and different levels of supervision on falls, and how this could be influenced by disease severity. Further work is also needed to increase the certainty of the effects of medication and further explore falls prevention education interventions both delivered alone and in combination with exercise.

Plain language summary

Interventions for preventing falls in Parkinson's disease

Review Question

In this review we assessed the evidence on the effect of interventions designed to reduce falls in people with Parkinson’s disease (PD). The interventions included exercise, medication, fall‐prevention education and exercise plus education combined. We excluded interventions that aimed to reduce falls due to syncope (e.g. dizziness and fainting). The evidence in this review is current to 16 July 2020.

Background

In people with PD, the emergence of frequent falls is one of the most serious disease milestones. Information about effective fall‐prevention strategies will aid the implementation of fall‐prevention interventions.

Study characteristics

We included 32 randomised controlled trials with 3370 participants. Of these, 25 studies with 2700 participants were exercise trials. Three studies with 242 participants were medication trials. One study with 53 participants was an education trial. Three studies with 375 participants were exercise plus education trials. Overall, the exercise and exercise plus education studies included people with mild to moderate PD.

Key results

Twelve studies compared exercise with a control intervention not thought to reduce falls. Exercise probably reduces the number of falls by around 26%. Exercise probably slightly reduces the number of people experiencing one or more falls by around 10%. Exercise may slightly improve health‐related quality of life immediately after the exercise program. However, we are uncertain if it reduces the number of fall‐related fractures, if it has an effect on the number of adverse events or if it is a cost‐effective intervention for fall prevention.

Three studies compared a cholinesterase inhibitor (either rivastigmine or donepezil) with placebo medication (an inactive treatment) and found that this medication may reduce the rate of falls by around 50%. However, the effect of this medication on the number of people experiencing one or more falls, and on health‐related quality of life was uncertain. Cholinesterase inhibitor medication may increase the number of non fall related adverse events by around 60%. There was no information about the cost‐effectiveness of medication for fall prevention.

One study compared education alone and three studies compared exercise plus education with a control group. Exercise plus education may make little or no difference to the number of people experiencing one or more falls. However, we are uncertain of the effects of these interventions on the other fall and non‐fall outcomes.

Certainty of the evidence

All studies had high or unclear risk of bias in at least one area. This could have influenced how the studies were conducted and how the outcomes were assessed.

For the exercise interventions, the certainty of the evidence for the rate of falls and the number of people experiencing one or more falls was moderate. The certainty of the evidence was low or very low for all other outcomes.

For medication, the education and the exercise plus education interventions, the certainty of the evidence was low to very low for all outcomes.

Summary of findings

Background

Description of the condition

People with Parkinson’s disease (PD) fall frequently and recurrently with approximately 60% of individuals falling each year and two thirds of these people falling recurrently (Allen 2013; Bloem 2001; Latt 2009; Paul 2013; Pickering 2007). These rates are double those reported for the general older population (Sherrington 2019). In addition, falls in people with PD are associated with injury (Paul 2017; Walker 2013; Wielinski 2005), with the incidence of hip fracture reported to be two (Kalilani 2016) to four times (Walker 2013) that of older people of the same age without PD. It is not surprising that falls are associated with escalating healthcare costs (Paul 2017; Pressley 2003), and are major contributors to reduced health‐related quality of life (Rascol 2015; Soh 2011).

A large number of fall risk factors have been identified in people with PD (Canning 2014; Fasano 2017) . Consistently identified risk factors include a history of past falls (Allcock 2009; Latt 2009; Paul 2013; Pickering 2007); disease severity (Allcock 2009; Kerr 2010; Latt 2009; Paul 2013; Pickering 2007), which are fixed and not remediable. However, a number of risk factors which contribute to loss of balance and falls have the potential to be modified with exercise or pharmaceutical interventions (Allen 2011; Fasano 2017; Shen 2016; Tomlinson 2013), which may in turn reduce falls. These include: freezing of gait (i.e. an episodic inability to initiate or continue walking) (Kerr 2010; Latt 2009; Paul 2013); balance deficits, mobility impairments and lower limb muscle strength deficits (Kerr 2010; Latt 2009; Paul 2013); fear of falling (Mak 2009), and cognitive deficits (Allcock 2009; Latt 2009; Paul 2013). While falls are commonly monitored as adverse events in intervention trials (Nieuwboer 2007; van Nimwegen 2013), only recently have interventions designed primarily to reduce falls in people with PD been developed and investigated (e.g. Canning 2015a; Chivers Seymour 2019; Li 2012; Mirelman 2016; Morris 2015).

Description of the intervention

Interventions designed to reduce falls in people with PD include exercise and/or movement strategy training, pharmacological and/or surgical management, increasing knowledge about fall prevention (education), environmental modifications, assistive technology, management of urinary incontinence, fluid or nutrition therapy, psychological interventions, social environment, and any other intervention designed to reduce falls in this population. Interventions are classified as single interventions (e.g. exercise), multiple interventions (e.g. exercise plus environmental modifications) or multifactorial interventions (i.e. multiple interventions tailored to the individual's identified risk factors).

How the intervention might work

Each intervention type is designed to target specific, potentially remediable fall risk factors. Exercise interventions aim to reduce falls by targeting physical and/or cognitive risk factors, including poor balance, reduced muscle strength and freezing of gait (Canning 2014; Mirelman 2016). Cholinesterase inhibitors address the central nervous system (CNS) cholinergic neuron loss associated with PD and may reduce falls by enhancing cognitive and attentional resources (Chung 2010), and/or reducing gait variability contributing to falls (Henderson 2016). Education interventions aim to increase awareness of the risk of falls and may include behaviour modification to avoid high‐risk activities (Stack 2013), while environmental modifications focus on reducing environmental hazards, such as poor lighting, or slippery surfaces (Bhidayasiri 2015).

Why it is important to do this review

Recently, a number of large‐scale randomised controlled trials and several smaller trials specifically testing interventions designed to reduce falls in people with PD have been published. In addition, participants with PD are excluded from the Cochrane Reviews of interventions for preventing falls in older people living in the community (Hopewell 2018; Sherrington 2019). Further, while falls as an outcome is addressed in Cochrane Reviews of physiotherapy interventions for PD (Tomlinson 2013; Tomlinson 2014), these reviews do not differentiate between physiotherapy interventions primarily designed to reduce falls versus other interventions. In addition, the scope of the physiotherapy reviews is limited to physical interventions. Therefore, there is a need to systematically review the literature to identify trials of all interventions aimed at reducing falls in people with PD and summarise this evidence for people with PD, clinicians, researchers and policymakers.

Objectives

To assess the effects of interventions designed to reduce the incidence of falls in people with Parkinson's disease (PD).

Methods

Criteria for considering studies for this review

Types of studies

We included randomised controlled trials (RCTs) and quasi‐randomised trials, including cluster‐ and cross‐over trials, evaluating the effects of interventions on falls in people with PD. Eligible randomised cross‐over trials of exercise interventions had the first phase data only included in order to minimise the risk of carry‐over effects of the interventions. For eligible randomised cross‐over trials of medication interventions we included data from both phases as washout phases ensured no carry‐over effects. We did not include studies published only in abstract form.

Types of participants

We included trials of participants with idiopathic PD who had been diagnosed by the UK Parkinson’s Disease Brain Bank criteria (Hughes 1992), or by a clinical definition. No restrictions were made with regard to gender, age or disease duration. We included studies reporting an intervention carried out in a mixed sample of participants, including people with idiopathic PD, if separate data were available for participants with idiopathic PD.

Types of interventions

We included interventions where a stated primary or secondary aim was to reduce falls in people with PD. Therefore, any intervention which did not have a stated aim of preventing falls, and which reported falls as an adverse event, was not included. We did not include interventions designed to primarily address syncopal falls (e.g. falls associated with neurogenic postural hypotension) as the aetiology and intervention for syncopal falls are different from falls arising from loss of balance due to physical, cognitive and emotional risk factors associated with PD (Fasano 2012; van der Marck 2014). We included studies where a fall‐prevention intervention was compared with ‘usual care’ (i.e. no change in usual activities or treatments), a ‘placebo’ or other control intervention (i.e. an intervention not thought to have an effect on falls, such as very gentle or 'sham' exercise), or another fall‐prevention intervention.

We grouped interventions using the fall‐prevention classification taxonomy developed by the Prevention of Falls Network Europe (ProFaNE) (Lamb 2011). Interventions were classified according to intervention type: exercises, medication (drug target, i.e. withdrawal, dose reduction or increase, substitution, provision), surgery, management of urinary incontinence, fluid or nutrition therapy, psychological interventions, environment/assistive technology, social environment, interventions to increase knowledge (education), or other interventions. Interventions were also classified according to combination of intervention types: single, multiple (more than one intervention type) or multifactorial (more than one intervention type specifically targeting person‐specific fall risk factors). Full details are available in the ProFaNE Taxonomy Manual (Lamb 2011).

We used the ProFaNE taxonomy (Lamb 2011) to categorise exercise types. Exercise categories were: i) gait, balance and functional training; ii) resistance training (including muscle power training); iii) flexibility exercise; iv) 3D exercise (e.g. Tai Chi); v) general physical activity; vi) endurance exercise, and vii) other forms of exercise (including where the exercise was not described in sufficient detail to allocate a category) (Table 7).

3. Exercise categories (based on ProFaNE): definition and application.

Exercise Category	ProFaNE exercise description	How the criteria were applied in this review*
Gait, balance and functional training	Gait training involves specific correction of walking technique (e.g., posture, stride length and cadence) and changes of pace, level and direction. Balance training involves the efficient transfer of bodyweight from one part of the body to another or challenges specific aspects of the balance systems (e.g. vestibular systems). Balance retraining activities range from the re‐education of basic functional movement patterns to a wide variety of dynamic activities that target more sophisticated aspects of balance. Functional training utilises functional activities as the training stimulus, and is based on the theoretical concept of task specificity. All gait, balance and functional training should be based on an assessment of the participant's abilities prior to starting the program; tailoring of the intervention to the individuals abilities; and progression of the exercise program as ability improves.	Selected as the primary exercise category when the majority of the exercise was conducted in standing and when the intervention focus and the majority of time spent was on exercise in this category. Movement strategy training and cueing are included in this category.
Resistance training	The term Resistance Training covers all types of weight training.i.e contracting the muscles against a resistance to overload and bring about a training effect in the muscular system. The resistance is an external force, which can be ones own body placed in an unusual relationship to gravity (e.g. prone back extension) or an external resistance (e.g. free weight). All strength/resistance training should be based on an assessment of the participant's abilities prior to starting the program; tailoring of the intervention to the individuals abilities; and progression of the exercise program as ability improves.	Selected as the primary category for interventions where additional resistance was used or where it was clear that overload was sufficient without external resistance and where the intervention focus and the majority of time spent was on exercise in this category.
Flexibility	Flexibility training is the planned process by which stretching exercises are practised and progressed to restore or maintain the optimal Range Of Movement (ROM) available to a joint or joints. The ranges of motion used by flexibility programs may vary from restoration/maintenance of the entire physiological range of motion, or alternatively, maintenance of range that is essential to mobility or other functions.	Selected as the primary category for interventions where flexibility training was a stated aim of the intervention and where the intervention focus and the majority of time spent was on exercise in this category.
3D	3D training involves constant movement in a controlled, fluid, repetitive way through all 3 spatial planes or dimensions (forward and back, side to side, and up and down). Tai Chi and Qi Gong incorporate specific weight transferences and require upright posture and subtle changes of head position and gaze direction. Dance involves a wide range of dynamic movement qualities, speeds and patterns.	Selected as the primary exercise category where the intervention focus and the majority of time was spent on exercise in this category (e.g., Tai Chi or dance).
General Physical activity	Physical activity is any bodily movement produced by skeletal muscle contraction resulting in a substantial increase in energy expenditure. Physical activity has occupational, transportation and recreational components and includes pursuits like golf, tennis and swimming. It also includes other activities and pastimes like gardening, cutting wood and carpentry. Physical activity can provide progressive health benefits and is a catalyst for improving health attitudes, health habits and lifestyle. Increasing habitual physical activity should be with specific recommendations as to duration, frequency and intensity if a physical or mental health improvement is indicated.	Selected as the primary category where the intervention focus and the majority of time was spent on exercise in this category (e.g. unstructured physical activity, including unstructured waking).
Endurance	Endurance training is aimed at cardiovascular conditioning and is aerobic in nature and simultaneously increases the heart rate and the return of blood to the heart.	Selected as the primary category for interventions where the intervention focus and the majority of time spent was on structured aerobic training (e.g. exercise with a target heart rate range).
Other	Other kind of exercises not described.	Selected as the primary category if the intervention did not meet the other categories listed and where the intervention focus and the majority of time was spent in this category. This category included interventions where the exercise was not described in sufficient detail to allocate a category.

Domain	Criteria for judging risk of bias
Random sequence generation: selection bias (biased allocation to interventions) due to inadequate generation of a randomised sequence	• Judgement of ’low risk’ if the trial authors described a random component in the sequence generation, e.g. referring to a random number table; using a computer random number generator; coin tossing; shuffling cards or envelopes; throwing dice; drawing of lots; minimisation. • Judgement of ’high risk’ if the trial used a systematic nonrandom method, e.g. date of admission; odd or even date of birth; case record number; clinician judgement; participant preference; patient risk factor score or test results; availability of intervention. • Judgement of ’unclear risk’ if there is insufficient information about the sequence generation process to permit judgement of ’low risk’ or ’high risk’.
Allocation concealment: selection bias (biased allocation to interventions) due to inadequate concealment of allocations prior to assignment	• Judgement of ’low risk’ in studies using: ◦ individual randomisation if the trial described allocation concealment as by central allocation (telephone, internet‐based or pharmacy‐controlled randomisation); sequentially‐numbered identical drug containers; sequentially numbered, opaque, sealed envelopes; ◦ cluster randomisation if allocation of all cluster units performed at the start of the study and individual participant recruitment was completed prior to assignment of the cluster, and the same participants were followed up over time or individual participants were recruited after cluster assignment, but recruitment carried out by a person unaware of group allocation and participant characteristics (e.g. fall history) or individual participants in intervention and control arms were invited by mail questionnaire with identical information. • Judgement of ’high risk’ in studies using: ◦ individual randomisation if investigators enrolling participants could possibly foresee assignments and thus introduce selection bias, e.g. using an open random allocation schedule (e.g. a list of random numbers); assignment envelopes unsealed, non‐opaque, or not sequentially numbered; alternation or rotation; date of birth; case record number; or any other explicitly unconcealed procedure; ◦ cluster‐randomisation if individual participant recruitment was undertaken after group allocation by a person who was unblinded and may have had knowledge of participant characteristics. • Judgement of ’unclear risk’ if insufficient information to permit judgement of ’low risk’ or ’high risk’. This is usually the case if the method of concealment is not described or not described in sufficient detail to allow a definite judgement, e.g. if the use of assignment envelopes is described, but it remains unclear whether envelopes were sequentially numbered, opaque and sealed.
Blinding of participants and personnel: performance bias due to knowledge of the allocated interventions by participants and personnel carrying out the interventions	• Judgement of ’low risk’ if blinding of participants and personnel implementing the interventions was ensured, and unlikely that the blinding could have been broken. • Judgement of ’high risk’ if participants or intervention delivery personnel, or both, were not blinded to group allocation (e.g. exercise intervention), and the outcomes (falls and fractures) are likely to be influenced by lack of blinding. • Judgement of ’unclear risk’ if there is insufficient information to make a judgement of ’low risk’ or ’high risk’.
Blinding of outcome assessment: detection bias due to knowledge of the allocated interventions by outcome assessors	• Falls, fallers: ◦ judgement of ’low risk’ if outcomes were recorded/confirmed in all allocated groups using the same method and the personnel recording/confirming outcomes were blind to group allocation; ◦ judgement of ’high risk’ if outcomes were not recorded/confirmed in all allocated groups using the same method or the personnel recording/confirming outcomes were NOT blind to group allocation; ◦ judgement of ’unclear’ if there is insufficient information to make a judgement of ’low risk’ or ’high risk’. • Fractures: ◦ judgement of ’low risk’ if fractures were recorded/confirmed in all allocated groups using the same method and fractures were confirmed by the results of radiological examination or from primary care case records and the personnel recording/confirming fractures were blind to group allocation; ◦ judgement of ’high risk’ if fractures were not recorded/ confirmed in all allocated groups using the same method or the only evidence for fractures was from self reports from participants or carers; ◦ judgement of ’unclear risk’ if there is insufficient information to make a judgement of ’low risk’ or ’high risk’.
Incomplete outcome data: attrition bias due to amount, nature or handling of incomplete outcome data	• Judgement of ’low risk’ if there are no missing outcome data, or less than 20% of outcome data are missing and losses are balanced in numbers across intervention groups with similar reasons for missing data across groups or missing data have been imputed using appropriate methods. • Judgement of ’high risk’ if greater than 20% of outcome data missing, or reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups, or ‘as treated’ analysis done with substantial departure of the intervention received from that assigned at randomisation or potentially inappropriate application of simple imputation. • Judgement of ’unclear risk’ if there is insufficient information to make a judgement of ’low risk’ or ’high risk’. See Appendix 2 for details
Selective reporting: reporting bias due to selective outcome reporting	• Judgement of ’low risk’ if the study protocol is available (i.e., published protocol or trial registry) and all prespecified study outcomes are reported in the prespecified way or the study protocol is unavailable, but it is clear the published report includes all expected outcomes. • Judgement of ’high risk’ if not all prespecified study outcomes are reported, or one or more primary outcomes are reported in ways which were not prespecified, or one or more outcomes are reported incompletely, or the study fails to include results for a key outcome that would be expected to be reported. • Judgement of ’unclear risk’ if there is insufficient information to make a judgement of ’low risk’ or ’high risk’.
Method of ascertaining falls: bias in the recall of falls due to unreliable methods of ascertainment	• Judgement of ’low risk’ if the study used some form of concurrent collection of data about falling, e.g. participants given postcards to fill in daily and mail back monthly, calendar to mark monthly, or more frequent, follow‐up by the researchers. • Judgement of ’high risk’ if ascertainment relied on participant recall at longer intervals than 1 month during the study or at its conclusion. • Judgement of ’unclear risk’ if there was retrospective recall over a short period only, or if the trial authors did not describe details of ascertainment, i.e. insufficient information was provided to allow a judgement of ’low risk’ or ’high risk’.

Study ID	Exercise description	Primary exercise category	Duration of exercise intervention (weeks)	Group/Individual	Location	% supervision*
Exercise trials
Ashburn 2007	Functional strength, range of movement, balance and walking exercise.	Gait, balance and functional training	6	Individual	Home‐based	18%
Canning 2015a	Functional strength, balance and cueing exercise (some participants attended monthly group classes).	Gait, balance and functional training	24	Both (most individual but some participants attended monthly exercise classes)	Both (most home‐based (but classes were held at a facility)	13%
Chivers Seymour 2019	Functional strength and balance exercise and strategies for fall and freezing avoidance.	Gait, balance and functional training	26	Individual	Home‐based	7%
Gandolfi 2017	Virtual reality balance training delivered via telehealth	Gait, balance and functional training	7	Group (pairs)	Home‐based	100%
Gandolfi 2017	Sensory‐integration balance training	Gait, balance and functional training	7	Individual	Facility‐based	100%
Gandolfi 2019	Trunk‐specific exercise	Gait, balance and functional training	4	Individual	Both	Unclear ‐ 100% at facility, number of unsupervised home‐sessions prescribed unclear
Gandolfi 2019	General exercise	Gait, balance and functional training	4	Individual	Both	Unclear ‐ 100% at facility, number of unsupervised home‐sessions prescribed unclear
Gao 2014	Tai Chi classes.	3D (Tai Chi)	12	Group	Facility‐based	100%
Goodwin 2011	Functional strength and balance exercise.	Gait, balance and functional training	10	Both	Both	33%
Harro 2014	Rhythmic auditory cued overground walking.	Gait, balance and functional training	6	Group	Facility‐based	100%
Harro 2014	Treadmill‐based gait training.	Gait, balance and functional training	6	Individual	Facility‐based	100%
Li 2012	Tai Chi classes.	3D (Tai Chi)	24	Group	Facility‐based	100%
Li 2012	Functional strength exercise with weighted vests and ankle weights.	Resistance training	24	Group	Facility‐based	100%
Martin 2015	Exercises to address freezing of gait and associated falls, and walking using cues.	Gait, balance and functional training	24	Individual	Home‐based	5%
Mirelman 2016	Treadmill training in a virtual reality environment.	Gait, balance and functional training	6	Individual	Facility‐based	100%
Mirelman 2016	Treadmill‐based gait training.	Gait, balance and functional training	6	Individual	Facility‐based	100%
Munneke 2010	Physiotherapy provided by ParkinsonNet therapists.	Other ‐ ParkinsonNet trained therapists	24	Individual	Unclear	ND
Munneke 2010	Physiotherapy usual care.	Other ‐ usual therapists	24	Individual	Unclear	ND
Paul 2014	Progressive lower limb muscle power training using strength training machines.	Resistance training	12	Group (pairs)	Facility‐based	100%
Pelosin 2017	High frequency treadmill training (5 times per week for 10 sessions)	Gait, balance and functional training	2	Individual	Facility‐based	100%
Pelosin 2017	Intermediate frequency treadmill training (3 times per week for 10 sessions)	Gait, balance and functional training	3.3	Individual	Facility‐based	100%
Pelosin 2017	Low frequency treadmill training (2 times per week for 10 sessions)	Gait, balance and functional training	5	Individual	Facility‐based	100%
Penko 2019	Gait and cognitive training practised together	Gait, balance and functional training	8	Individual	Facility‐based	100%
Penko 2019	Gait and cognitive training practised separately	Gait, balance and functional training	8	Individual	Facility‐based	100%
Protas 2005	Gait and stepping training.	Gait, balance and functional training	8	Individual	Facility‐based	100%
Ricciardi 2015	Strength, balance and gait training targeting the more affected side.	Gait, balance and functional training	12	Unclear	Facility‐based	100%
Ricciardi 2015	Strength, balance and gait training targeting the less affected side.	Gait, balance and functional training	12	Unclear	Facility‐based	100%
Ricciardi 2015	Functional strength, balance and gait training.	Gait, balance and functional training	12	Unclear	Facility‐based	100%
Sedaghati 2016	Progressive balance and gait training with a balance pad (i.e. foam to stand on).	Gait, balance and functional training	10	Unclear	Facility‐based	100%
Sedaghati 2016	Progressive balance and gait training without a balance pad.	Gait, balance and functional training	10	Unclear	Facility‐based	100%
Shen 2015	Balance and gait training.	Gait, balance and functional training	12	Unclear	Both	55%
Shen 2015	Lower limb resistance training using strength training machines (facility) and functional strength training (home)	Resistance training	12	Unclear	Both	55%
Smania 2010	Balance exercises.	Gait, balance and functional training	7	Individual	Facility‐based	100%
Smania 2010	Flexibility and coordination exercises not aimed at improving balance.	Flexibility	7	Individual	Facility‐based	100%
Song 2018	Stepping videogame exercise	Gait, balance and functional training	12	Individual	Home‐based	8%
Thaut 2019	Gait training with rhythmic auditory stimulation throughout intervention period	Gait, balance and functional training	24	Individual	Home‐based	Unclear
Thaut 2019	Gait training with rhythmic auditory stimulation, with no training in middle 8 weeks of intervention period	Gait, balance and functional training	16	Individual	Home‐based	Unclear
Volpe 2014a	Balance training using external perturbations wearing a proprioceptive stabiliser.	Gait, balance and functional training	8	Individual	Facility‐based	100%
Volpe 2014a	Balance training using external perturbations with a sham proprioceptive stabiliser.	Gait, balance and functional training	8	Individual	Facility‐based	100%
Volpe 2014b	Hydrotherapy with perturbation‐based balance training.	Gait, balance and functional training	8	Unclear	Facility‐based	100%
Volpe 2014b	Land‐based therapy with perturbation‐based balance training.	Gait, balance and functional training	8	Unclear	Facility‐based	100%
Wong‐Yu 2015	Strength and balance exercise, including dance and modified Wing Chun martial art.	Gait, balance and functional training	8	Both	Both	40%
Exercise plus education trials
Cattaneo 2019	Tailored mobility and balance exercises (plus fall prevention education).	Gait, balance and functional training	8	Individual	Home‐based	14%
Morris 2015	Functional progressive resistance training with weighted vests and resistance bands.	Resistance training	8	Individual	Both	50%
Morris 2015	Movement strategy training.	Gait, balance and functional training	8	Individual	Both	50%
Morris 2017	Functional strength, movement strategy training (plus falls prevention education).	Gait, balance and functional training	6	Individual	Home‐based	50%

Study ID and comparison	Source for rate ratio: rate of falls	Source for risk ratio: number of fallers	Source for risk ratio: number with fractures	Source for risk ratio: number with adverse events
Exercise trials
Ashburn 2007 Gait, balance and functional training vs Control	3*	7	7	NA
Canning 2015a⁺ Gait, balance and functional training vs Control	1	5	7	NA
Chivers Seymour 2019^‡ Gait, balance and functional training vs Control	1a⁺⁺	NA	7	NA
Gandolfi 2017 Gait, balance and functional training (virtual reality telerehabilitation) vs Gait, balance and functional training (balance training in a facility)	3^‡‡‡	NA	NA	NA
Gandolfi 2019 Gait, balance and functional training (trunk‐specific exercises) vs Gait, balance and functional training (general exercises)	3^‡‡‡	NA	NA	NA
Gao 2014 3D exercise (Tai Chi) vs Control	3	7	NA	NA
Goodwin 2011^‡‡ Gait, balance and functional training vs Control	1a⁺⁺	6a	7	NA
Harro 2014 Gait, balance and functional training (cueing training) vs Gait, balance and functional training (treadmill‐based gait training)	3	7	NA	NA
Li 2012 3D exercise (Tai Chi) vs Resistance training (functional strength) and 3D exercise (Tai Chi) vs Control	1	7	NE	NA
Li 2012 Resistance training (functional strength) vs Control	3	7	NE	NA
Martin 2015 Gait, balance and functional training vs Control	1*	7	NA	NA
Mirelman 2016 Gait, balance and functional training (virtual reality treadmill training) vs Gait, balance and functional training (treadmill‐based gait training)	1a	NA	NA	NA
Munneke 2010 Other exercise (ParkinsonNet therapists) vs Other exercise (standard therapists)	3c	NA	NA	NA
Paul 2014 Resistance training vs Control	1**	5	7	NA
Pelosin 2017 Gait, balance and functional training (treadmill training at high frequency) vs Gait balance and functional training (treadmill training at intermediate frequency) vs Gait, balance and functional training (treadmill training at low frequency)	3^‡‡‡	NA	NA	NA
Penko 2019 Gait, balance and functional training (Gait and cognitive training practised together) vs Gait, balance and functional training (Gait and cognitive training practised separately)	3^‡‡‡	NA	NA	NA
Protas 2005 Gait, balance and functional training vs Control	3	7	NA	NA
Ricciardi 2015 Gait, balance and functional training (best side therapy) vs Gait, balance and functional training (worst side therapy) vs Gait, balance and functional training (standard therapy)	3	NA	NA	NA
Sedaghati 2016 Gait, balance and functional training (with a balance pad) vs Gait, balance and functional training (without a balance pad) vs Control	3	NA	NA	NA
Shen 2015*** Gait, balance and functional training vs Resistance training	1a	7	7	NA
Smania 2010 Gait, balance and functional training vs Flexibility exercise	3	NA	NA	NA
Song 2018 Gait, balance and functional training vs Control	1	7	NA	NA
Thaut 2019 Gait, balance and functional training (rhythmic auditory stimulation training throughout intervention period) vs Gait, balance and functional training (rhythmic auditory stimulation training with no training in middle 8 weeks of intervention period)	NA	7	NA	NA
Volpe 2014a Gait, balance and functional training (with proprioceptive stabiliser) vs Gait, balance and functional training (without proprioceptive stabiliser)	3	NA	NA	NA
Volpe 2014b Gait, balance and functional training (hydrotherapy) vs Gait, balance and functional training (land‐based therapy)	3	NA	NE	NA
Wong‐Yu 2015 Gait, balance and functional training vs Control	1	6	NA	NA
Medication trials
Chung 2010 Donepezil vs placebo	3	7	NE	3
Henderson 2016 Rivastigmine vs placebo	1*	7	NA	3
Li 2015a Rivastigmine vs placebo	3	6	NA	ND
Education trial
Ward 2004 Personalised education vs control (standardised printed information)	NA	6a	NA	NA
Exercise plus education trials
Cattaneo 2019 Gait, balance and functional training + education vs Control	NA	4	NA	NA
Morris 2015 Resistance training (functional strength) + education vs Control and Gait, balance and functional training (movement strategy training) + education vs Control	1	5	7	NA
Morris 2015 Resistance training (functional strength) + education vs Gait, balance and functional training (movement strategy training) + education	3	7	7	NA
Morris 2017 Gait, balance and functional training + education vs Control	1	5	7	NA

Study ID and comparison	Intervention group: falls per person year	Intervention group: number (%) of fallers	Intervention group: number (%) of people sustaining one or more fall‐related fractures	Intervention group: non‐fall‐related adverse events per person year	Intervention group: number in analysis	Control group: falls per person year	Control group: number (%) of fallers	Control group: number (%) of people sustaining one or more fall‐related fractures	Control group: non‐fall‐related adverse events per person year	Control group: number in analysis	Length of falls/adverse events monitoring
Exercise trials
Ashburn 2007 Gait, balance and functional training vs Control	6.3	46 (73%)	2 (3%)	NA	Rate of falls and number of fallers: 63 Number sustaining fracture: 67	7.9*	49 (78%)	6 (9%)	NA	Rate of falls: 62 Number of fallers: 63 Number sustaining fracture: 67	6 months
Canning 2015a Gait, balance and functional training vs Control	8.2	75 (65%)	3 (3%)	NA	115	14.0	81 (70%)	4 (3%)	NA	116	6 months
Chivers Seymour 2019 Gait, balance and functional training vs Control	0‐6 months: 6.8 6‐12 months: 5.4	NA	0‐6 months: 5 (2%) 6‐12 months: 7 (5%)	NA	0‐6 months: 231 6‐12 months: 127	0‐6 months: 5.4 6‐12 months: 5.6	NA	0‐6 months: 9 (4%) 6‐12 months: 3 (2%)	NA	0‐6 months: 230 6‐12 months: 147	12 months, divided into 0‐6 and 6‐12 month time periods
Gandolfi 2017 Gait, balance and functional training (virtual reality telerehabilitation) vs Gait, balance and functional training (balance training in a facility)	4.0/8.5	NA	NA	NA	36/34	NA	NA	NA	NA	NA	2 months^‡‡
Gandolfi 2019 Gait, balance and functional training (trunk‐specific exercises) vs Gait, balance and functional training (general exercises)	6.3/2.9	NA	NA	NA	19/18	NA	NA	NA	NA	NA	2 months^‡‡
Gao 2014 3D exercise (Tai Chi) vs Control	0.6	8 (22%)	NA	NA	37	1.3	19 (49%)	NA	NA	39	6 months
Goodwin 2011 Gait, balance and functional training vs Control	0‐10 weeks: 93.9 10‐20 weeks: 34.5	0‐20 weeks: 52 (85%)	0‐20 weeks: 0 (0%)	NA	61	0‐10 weeks: 168.1 10‐20 weeks: 155.4	0‐20 weeks: 55 (86%)	0‐20 weeks: 1 (2%)	NA	64	20 weeks
Harro 2014 Gait, balance and functional training (cueing training) / Gait, balance and functional training (treadmill‐based gait training)	0.4/1.0	2 (20%)/4 (40%)	NA	NA	10/10	NA	NA	NA	NA	NA	6 months
Li 2012 3D exercise (Tai Chi) / Resistance training vs Control	1.9/4.1	19 (29%)/31 (48%)	0 (0%)/0 (0%)	NA	65/65	5.7	26 (40%)	0 (0%)	NA	65	6 months
Martin 2015 Gait, balance and functional training vs Control	166.4 (using fall rate data from week 24‐28)*	10 (100%)	NA	NA	Fall rate: 9 Number of fallers: 10	140.4 (using fall rate data from week 24‐28)	9 (100%)	NA	NA	Fall rate: 8 Number of fallers: 9	6 months
Mirelman 2016 Gait, balance and functional training (virtual reality treadmill training) / Gait, balance and functional training (treadmill‐based gait training)	ND	NA	NA	NA	66/64	NA	NA	NA	NA	NA	6 months
Munneke 2010 Other exercise (ParkinsonNet therapists) / Other exercise (standard therapists)	1.5/1.4	NA	NA	NA	329/312	NA	NA	NA	NA	NA	24 weeks
Paul 2014 Resistance training vs Control	6.5	7 (37%)	1 (5%)	NA	19	11.6	12 (63%)	0 (0%)	NA	19	6 months
Pelosin 2017 Gait, balance and functional training (treadmill training at high frequency) vs Gait balance and functional training (treadmill training at intermediate frequency) vs Gait, balance and functional training (treadmill training at low frequency)	Unclear, as timeframe for falls monitoring not reported	NA	NA	NA	10/10/10	NA	NA	NA	NA	NA	Unclear
Penko 2019 Gait, balance and functional training (Gait and cognitive training practised together) vs Gait, balance and functional training (Gait and cognitive training practised separately)	9.1/8.2	NA	NA	NA	10/9	NA	NA	NA	NA	NA	2 months^‡‡
Protas 2005 Gait, balance and functional training vs Control	23.1	5 (56%)	ND	NA	9	37.6	6 (67%)	ND	NA	9	2 weeks
Ricciardi 2015 Gait, balance and functional training (best side therapy) / Gait, balance and functional training (worst side therapy) / Gait, balance and functional training (standard therapy)	11.1/7.2/4.9	NA	NA	NA	9/9/9	NA	NA	NA	NA	NA	16 weeks
Sedaghati 2016 Gait, balance and functional training (with a balance pad) / Gait, balance and functional training (without a balance pad) vs Control	1.04/4.16	NA	NA	NA	15/14	7.8	NA	NA	NA	15	10 weeks
Shen 2015 Gait, balance and functional training / Resistance training	0.41/1.02	6 (27%)/13 (57%)	1 (5%)/1 (4%)	NA	Fall rate: 21/21 Number of fallers and fractures: 22/23	NA	NA	NA	NA	NA	15 months
Smania 2010 Gait, balance and functional training / Flexibility exercise	15.6/49.2	NA	NA	NA	28/27	NA	NA	NA	NA	NA	1 month
Song 2018 Gait, balance and functional training vs Control	9.4	16 (55%)	NA	NA	29	8.6	17 (68%)	NA	NA	25	6 months
Thaut 2019 Gait, balance and functional training (rhythmic auditory stimulation training throughout intervention period) vs Gait, balance and functional training (rhythmic auditory stimulation training with no training in middle 8 weeks of intervention period)	NA	24 (96%)/22 (100%)	NA	NA	25/22	NA	NA	NA	NA
Volpe 2014a Gait, balance and functional training (with proprioceptive stabiliser) / Gait, balance and functional training (without proprioceptive stabiliser)	11.4/18.6	NA	NA	NA	20/20	NA	NA	NA	NA	NA	4 months
Volpe 2014b Gait, balance and functional training (hydrotherapy) / Gait, balance and functional training (land‐based therapy)	3.6/9.6	NA	0 (0%)/0 (0%)	NA	17/17	NA	NA	NA	NA	NA	2 months
Wong‐Yu 2015 Gait, balance and functional training vs Control	0.38	6 (19%)	NA	NA	32	0.38	8 (22%)	NA	NA	36	6 months
Medication trials
Chung 2010 Donepezil vs placebo⁺	47.45	18 (95%)	0 (0%)	3.0	Fall rates and number of fallers and fractures:19 Adverse events: 23	91.25	16 (84%)	0 (0%)	1.1	Fall rates and number of fallers and fractures: 19 Adverse events: 23	12 weeks
Henderson 2016 Rivastigmine vs placebo	16.8*	56 (86%)	NA	4.4	Fall rate and adverse events: 64 Number of fallers and fractures:65	28.8	56 (86%)	NA	2.8	65	8 months
Li 2015a Rivastigmine vs placebo	1.82	13 (32%)	NA	ND	41	4.26	24 (60%)	NA	ND	40	12 months
Education trial
Ward 2004 Personalised education vs control (standardised printed information)	NA	ND	NA	NA	27	NA	ND	NA	NA	26	12 months
Education plus exercise trials
Cattaneo 2019 Gait, balance and functional training plus education vs Control	NA	ND	NA	NA	15	NA	ND	NA	NA	17	6 months
Morris 2015 Resistance training / Gait, balance and functional training (movement strategy training) vs Control	2.8/6.6	36 (52%)/44 (66%)	3 (4%)/3 (4%)	NA	69/67	18.6	37 (63%)	2 (3%)	NA	59	12 months
Morris 2017 Gait, balance and functional training plus education vs Control	21.9	39 (61%)	2 (3%)	NA	64	14.2	43 (72%)	1 (2%)	NA	60	12 months

Study ID and groups	Intervention group: Number of participants	Intervention group: falls per person year	Intervention group: number (%) of fallers	Control group: number of participants	Control group: falls per person year	Control group: number (%) of fallers	Randomisation stratified by fall history	Timeframe for baseline falls monitoring
Exercise trials
Ashburn 2007 Gait, balance and functional training vs Control	70	60	70 (100%)	72	61	72 (100%)	No	12 months, measured retrospectively
Canning 2015a Gait, balance and functional training vs Control	115	2	90 (78%)	116	2	90 (78%)	Yes	12 months, measured retrospectively
Chivers Seymour 2019 Gait, balance and functional training vs Control	3 months prospective: 237 12 months retrospective: 238	3 months prospective: 23.6 12 months retrospective: 26	12 months retrospective: 238 (100%)	3 months prospective and 12 months retrospective: 236	3 months prospective: 12 12 months retrospective: 19	236 (100%)	No	3 months, measured prospectively prior to commencing intervention and 12 months, measured retrospectively
Gandolfi 2017 Gait, balance and functional training (virtual reality telerehabilitation) vs Gait, balance and functional training (balance training in a facility)	38/38	6.9/22.1	ND	NA	NA	NA	No	1 month, unclear if measured prospectively or retrospectively
Gandolfi 2019 Gait, balance and functional training (trunk‐specific exercises) vs Gait, balance and functional training (general exercises)	19/18	19.6/7.9	ND	NA	NA	NA	No	1 month, unclear if measured prospectively or retrospectively
Gao 2014 3D exercise (Tai Chi) vs Control	40	ND	ND	40	ND	ND	No	ND
Goodwin 2011 Gait, balance and functional training vs Control	Rate of falls analysis: 60 Number of fallers analysis: 64	137.8	55 (86%)	Rate of falls analysis: 62 Number of fallers analysis: 66	156.2	54 (82%)	No	10 weeks, measured prospectively prior to commencing intervention
Harro 2014 Gait, balance and functional training (cueing training) / Gait, balance and functional training (treadmill‐based gait training)	10/10	1/1.4	3 (30%)/5 (50%)	NA	NA	NA	No	6 months, measured retrospectively
Li 2012 3D exercise (Tai Chi) / resistance training (functional strength) vs Control	65/65	ND	ND	65	ND	ND	No	ND
Martin 2015 Gait, balance and functional training vs Control	Rate of falls analysis: 11* Number of fallers analysis: 12	202.8	9 (75%)	9	150.8	6 (67%)	No	5 weeks, measured prospectively from the point of study entry ‐ unclear if this overlaps with the first 3 weeks of the intervention period
Mirelman 2016 Gait, balance and functional training (virtual reality treadmill training) / Gait, balance and functional training (treadmill‐based gait training)	66/64	36.5/38.5	66 (100%)/64 (100%)	NA	NA	NA	No	6 months, measured retrospectively
Munneke 2010 Other exercise (ParkinsonNet therapists) / Other exercise (standard therapists)	358/341	ND	ND	NA	NA	NA	No	ND
Paul 2014 Resistance training vs Control	20	ND	5 (25%)	20	ND	7 (35%	No	12 months, measured retrospectively
Pelosin 2017 Gait, balance and functional training (treadmill training at high frequency) vs Gait balance and functional training (treadmill training at intermediate frequency) vs Gait, balance and functional training (treadmill training at low frequency)	10/10/10	Unclear, as timeframe for falls monitoring not reported	NA	NA	NA	NA	No	Unclear
Penko 2019 Gait, balance and functional training (Gait and cognitive training practised together) vs Gait, balance and functional training (Gait and cognitive training practised separately)	10/9	28/7.4	ND	NA	NA	NA	No	30 days, measured retrospectively
Protas 2005 Gait, balance and functional training vs Control	9	66.4	5 (56%)	9	66.4	6 (67%)	No	2 weeks, measured prospectively
Ricciardi 2015 Gait, balance and functional training (best side therapy) / Gait, balance and functional training (worst side therapy) / Gait, balance and functional training (standard therapy)	9/9/10	ND	ND	NA	NA	NA	No	ND
Sedaghati 2016 Gait, balance and functional training (with a balance pad) / Gait, balance and functional training (without a balance pad) vs Control	15/14	6.8/6.7	ND	15	6.2	ND	No	10 weeks, unclear if measured retrospectively or prospectively
Shen 2015 Gait, balance and functional training / Resistance training	22/23	0.57/0.76**	9 (41%)/10 (43%)	NA	NA	NA	No	12 months, measured retrospectively
Smania 2010 Gait, balance and functional training / Flexibility exercise	28/27	51.6/55.2	ND	NA	NA	NA	No	1 month, measured prospectively
Song 2018 Gait, balance and functional training vs Control	31	ND	17 (55%)	29	ND	16 (55%)	No	6 months, measured retrospectively
Thaut 2019 Gait, balance and functional training (rhythmic auditory stimulation training throughout intervention period) vs Gait, balance and functional training (rhythmic auditory stimulation training with no training in middle 8 weeks of intervention period)	25/22	4.5/4.2	ND	NA	NA	NA	No	12 months, measured retrospectively
Volpe 2014a Gait, balance and functional training (with proprioceptive stabiliser) / Gait, balance and functional training (without proprioceptive stabiliser)	20/20	ND	16 (80%)/12 (60%)	NA	NA	NA	No	2 months, measured prospectively
Volpe 2014b Gait, balance and functional training (hydrotherapy) / Gait, balance and functional training (land‐based therapy)	17/17	18/12.6	17 (100%)/17 (100%)	NA	NA	NA	No	Rate of falls: 2 months, measured prospectively Number of fallers: 12 months, measured retrospectively
Wong‐Yu 2015 Gait, balance and functional training vs Control	32	0	0 (0%)	38	0	0 (0%)	No	6 months, measured retrospectively
Medication trials
Chung 2010 Donepezil vs placebo	19	ND	19 (100%)	19	ND	19 (100%)	No	Unclear: participants had all fallen or nearly fallen 2 or more times per week, measured retrospectively
Henderson 2016 Rivastigmine vs placebo	65	5.0	65 (100%)	65	5.5	65 (100%)	No	12 months, measured retrospectively
Li 2015a Rivastigmine vs placebo	41	3.6	22 (54%)	40	3.8	23 (58%)	No	Unclear
Education trial
Ward 2004 Personalised education vs control (standardised printed information)	27	ND	ND	26	ND	ND	No	ND
Exercise plus education trials
Cattaneo 2019 Gait, balance and functional training plus education vs Control	15	ND	ND	17	ND	ND	No	ND
Morris 2015 Resistance training (functional strength) / Gait, balance and functional training (movement strategy training) vs Control	70/69	ND	38 (54%)/40 (58%)	71	ND	38 (54%)	No	12 months, measured retrospectively
Morris 2017 Gait, balance and functional training plus education vs Control	67	ND	38 (57%)	66	ND	35 (53%)	No	12 months, measured retrospectively

Study ID and comparison	Intervention group baseline n, mean (SD)	Control group baseline n, mean (SD)	Intervention group post timeframe, n, mean (SD)	Control group post timeframe, n, mean (SD)	Intervention group follow‐up timeframe, n, mean (SD)	Control group follow‐up timeframe, n, mean (SD)
Exercise trials
Parkinson’s Disease Questionnaire 39 (PDQ39) and 8 (PDQ8) (range 0‐100)*
Canning 2015a Gait, balance and functional training vs Control	115, 28 (13.9)	116, 30.7 (15.4)	26 weeks, 104, 29.7 (14.8)	26 weeks, 115, 32.5 (15.9)	NA	NA
Chivers Seymour 2019 Gait, balance and functional training vs Control	126, 27.4 (14.3)	153, 28.7 (15.9)	6 months, 126, 28.3 (15.0)	6 months, 153, 29.5 (16.5)	12 months, 77, 29.1 (15.4)	12 months, 100, 31.7 (15.5)
Gandolfi 2017 (PDQ8) Gait, balance and functional training (virtual reality telerehabilitation) vs Gait, balance and functional training (balance training in a facility)	36, 30.7 (15.5)/ 34, 30.5 (16.0)	NA	7 weeks, 36, 24.1 (14.8)/ 34, 24.2 (15.9)	NA	11 weeks, 36, 25.8 (14.9)/ 34, 23.9 (13.2)	NA
Gandolfi 2019 (PDQ8) Gait, balance and functional training (trunk‐specific exercises) vs Gait, balance and functional training (general exercises)	19, 25.5 (11.8)/ 18, 18.7 (10.8)	NA	4 weeks, 19, 21.5 (10.0)/ 18, 15.3 (8.6)	NA	8 weeks, 19, 23.0 (12.6)/ 18, 21.0 (8.8)	NA
Harro 2014 Gait, balance and functional training (cueing training) / Gait, balance and functional training (treadmill‐based gait training)	11, 31.1 (14.8)/ 11, 40.1 (17.5	NA	6 weeks, 10, 27.5 (17.9)/ 10, 27.4 (10.0)	NA	3 months, 10, 25.4 (15.0)/ 9, 30.0 (12.9)	NA
Li 2012 (PDQ8) 3D exercise (Tai Chi) / Resistance training vs Control	65, 25.1 (16.8)/ 65, 25.3 (14.7)	65, 25.2 (16.3)	6 months, 65, 15.5 (11.4)/ 65, 21.4 (12.7)	6 months, 65, 25.1 (15.6)	NA	NA
Volpe 2014a** Gait, balance and functional training (with proprioceptive stabiliser) / Gait, balance and functional training (without proprioceptive stabiliser)	20, 62.7 (19.5)/ 20, 61.4 (38.9)	NA	2 months, 20, 44.0 (22.3)/ 20, 58.5 (37.9)	NA	4 months, 20, 53.7 (22.3)/ 20, 61.0 (35.1)	NA
Volpe 2014b Gait, balance and functional training (hydrotherapy) / Gait, balance and functional training (land‐based therapy)	17, 60.3 (19.9)/ 17, 64.4 (28.6)	NA	2 months 17, 41.9 (20.9)/ 17, 56.4 (26.8)	NA	NA	NA
EQ5D Thermometer (0‐100)
Ashburn 2007 Gait, balance and functional training vs Control	70, 63.1 (17.1)	71, 64.6 (14.5)	8 weeks, 67, 61.3 (19.8)	8 weeks, 66, 61.7 (14.5)	6 months, 65, 63.0 (18.7)	6 months, 64, 56.6 (16.9)
EQ5D Index score (range 0‐1)
Goodwin 2011** Gait, balance and functional training vs Control	61, 0.7 (0.1)	63, 0.7 (0.1)	10 weeks, 61, 0.7 (0.1)	10 weeks, 63, 0.7 (0.1)	20 weeks, 61, 0.8 (0.3)	20 weeks, 62, 0.7 (0.3)
Munneke 2010 Other exercise (ParkinsonNet therapists) / Other exercise (standard therapists)	358, 0.65 (0.20)/ 341, 0.65 (0.22)	NA	16 weeks, 295, 0.66 (0.20)/ 294, 0.65 (0.23)	NA	24 weeks, 262, 0.68 (0.21)/ 259, 0.66 (0.23)	NA
SF12 and SF36 Physical Composite Score (range 0‐100)
Canning 2015a (SF12) Gait, balance and functional training vs control	115, 42.3 (7.6)	116, 42.9 (7.9)	26 weeks, 104, 41.3 (8.8)	26 weeks, 115, 40.2 (7.8)	NA	NA
Mirelman 2016 (SF36) Gait, balance and functional training (virtual reality treadmill training) / Gait, balance and functional training (treadmill‐based gait training)	66, 49 (2.5)/ 64, 44.8 (2.5)	NA	6 weeks, 66, 52 (2.5)/ 64, 46.5 (2.5)	NA	6 months, 66, 50.5 (2.5)/ 64, 48 (2.5)	NA
SF12 Mental Composite Score (range 0‐100)
Canning 2015a Gait, balance and functional training vs Control	115, 51.6 (6.5)	116, 50.5 (6.8)	26 weeks, 104, 51.2 (6.4)	26 weeks, 115, 50.3 (6.7)	NA	NA
Medication Trials
EQ5D Thermometer (0‐100)
Henderson 2016 Rivastigmine vs placebo	65, 64 (17)	65, 65 (17)	32 weeks, 58, 66 (16)	32 weeks, 63, 63 (18)	NA	NA
EQ 5D Index score (range 0‐1)
Henderson 2016 Rivastigmine vs placebo	65, 0.72 (0.19)	65, 0.71 (0.18)	32 weeks, 58, 0.66 (0.21)	32 weeks, 63, 0.66 (0.19)	NA	NA
Education plus exercise trials
Parkinson’s Disease Questionnaire 39 (PDQ39) (range 0‐100)*
Morris 2015 Resistance training / Gait, balance and functional training (movement strategy training) vs Control	70, 20.8 (13.6)/ 69, 19.4 (12.8)	71, 22.1 (12.5)	3 months, 67, 18.9 (13.5)/ 64, 16.9 (14.0)	3 months, 54, 18.5 (12.6)	14 months, 67, 20.0 (13.6)/ 66, 20.8 (14.1)	14 months, 57, 24.1 (13.1)
Morris 2017 Gait, balance and functional training plus education vs Control	67, 23 (14)	66, 24 (15)	6 weeks, 62, 21 (14)	6 weeks, 58, 20 (14)	58 weeks, 55, 22 (13)	58 weeks, 53, 22 (14)
EQ5D Thermometer (0‐100)
Morris 2015 Resistance training / Gait, balance and functional training (movement strategy training) vs Control	70, 74.1 (16.7)/ 69, 73.9 (15.9)	71, 72.7 (14.6)	3 months, 67, 71.8 (16.4)/ 64, 76.5 (16.4)	3 months, 54, 74.7 (16.0)	14 months, 67, 75.4 (14.1)/ 66, 75.0 (13.5)	14 months, 57, 72.8 (16.0)
Morris 2017 Gait, balance and functional training vs Control	67, 73 (15)	66, 72 (16)	6 weeks, 62, 68 (15)	6 weeks, 58, 76 (12)	58 weeks, 55, 72 (17)	58 weeks, 53, 71 (14)
EQ5D Index score (range 0‐1)
Morris 2017 Gait, balance and functional training vs Control	67, 0.67 (0.27)	66, 0.63 (0.28)	6 weeks, 62, 0.66 (0.29)	6 weeks, 58, 0.65 (0.27)	58 weeks, 55, 0.67 (0.25)	58 weeks, 53, 0.64 (0.3)

Study ID, (source if not primary reference), sample, comparison, type of evaluation	Intervention(s) and comparator (n in analyses)	Perspectives, type of currency, price year, time horizon	Cost items measured	Intervention costs per participant	Healthcare service costs per participant	Incremental cost per fall prevented/ per QALY gained
Exercise trials
Canning 2015a (Farag 2016) People with PD who had fallen at least once in the past year or were at risk of falls. Gait, balance and functional training vs control Evaluated with cost‐effectiveness analyses	Exercise (balance, lower limb strength, and when required cueing), 3 X week, 24 weeks, with 6‐10 sessions supervised either individually or in a group setting (n = 113) vs usual care control (n = 113)	Health system perspective, Australian dollar, 2012, During 6‐month trial period	Intervention costs (staff time, travel, equipment) Health service use costs (hospital, medical, allied health) Medication costs	$A1,010 (€642)	Exercise group $A4,604 (€2,925) Control group $A3,920 (€2,491)	Cost per fall prevented $A574 (€365) Cost per QALY gained $A338,800 (€215,277)
Chivers Seymour 2019 (Ashburn 2019, Xin 2020) People with PD who had fallen at least once in the past year. Gait, balance and functional training vs control Evaluated with cost‐effectiveness analyses	Exercise (balance and lower limb strengthening exercises, plus strategies for preventing falls and reducing freezing of gait), 30 min per day for 6 months, including 12 x 1‐1.5 hour supervised sessions with a physiotherapist (n = 238) vs usual care control (n = 236)	United Kingdom National Health Service and Personal Social Services perspectives, Pound Stirling, 2016, During 6 month intervention period	Intervention costs (physiotherapist salaries, training, travel, equipment and consumables) Health service use (hospital, primary care, social service) Medication costs collected but not included in analyses	£650 (€765)	Exercise group £3,137 (€3,905) Control group £3,069 (€3,613)	Cost per QALY gained £120,659 (€142,063)
Gandolfi 2017 People with PD, both fallers and non‐fallers. Gait, balance and functional training (virtual reality telerehabilitation) vs Gait, balance and functional training (balance training in a facility) Evaluated with cost analysis	Virtual reality balance training (using Nintendo Wii Fit system, Nintendo Co., Ltd., Kyoto, Japan) delivered via telehealth (using Skype, Microsoft, USA), delivered in pairs (n = 36) vs sensory‐integration balance training delivered in‐person, individually (n = 34), both interventions 50 mins, 3 X week, 7 weeks	Cost of rehabilitation perspective, Euros, Price year not reported, During assessments and 7 week intervention period	Direct costs (personnel for screening, assessments and intervention, plus resource utilisation). Indirect costs (utilities, facilities)	Virtual reality via telehealth balance training (delivered in pairs) €383.55 sensori‐integration balance training (delivered individually) €602.10	Not reported	Not reported
Goodwin 2011 (Fletcher 2012) People with PD and 2 or more falls in the preceding year. Gait, balance and functional training vs control Evaluated with cost‐effectiveness analyses	Exercise (balance, lower limb and trunk strength, 1 X week supervised group and 2 X week independent at home for 10 weeks (n=48) vs usual care control (n = 45). Economic analyses conducted with intervention n = 48 and control n = 45	United Kingdom National Health Service and Personal Social Services perspectives, Pound sterling, 2008/9, During 20 weeks (10 weeks intervention and 10 weeks follow‐up)	Intervention costs (staff time, travel, equipment, venue hire) Health service use (hospital, primary care, social service) Medication costs	£76 (€89)	Exercise group Health care cost £1,198 (€1,410) Health and social care cost £1,444 (€1,700) Control group Health care cost £1,320 (€1,554) Health and social care cost £1,479 (€1,741)	Cost per QALY gained for total health care costs ‐£4,885 (‐€5,752) Cost per QALY gained for combined total health care and social care costs ‐£1,358 (‐€1,599)
Li 2012 (Li 2015b) People with PD, both fallers and non‐fallers. 3D exercise (Tai Chi) / resistance training (functional strength) vs control Evaluated with cost‐effectiveness analyses	Tai Chi (n=65) vs resistance training (n=65) vs stretching (control) (n=65), all group classes for 60 minutes, 2 X week, 24 weeks	Societal perspective, United States dollar, 2011, During 9 months (6 months intervention and 3 months follow‐up)	Intervention costs (program promotion, recruitment, staff time, insurance, equipment, room hire, printed materials) Non‐intervention costs (PD medication, physical therapy, medical treatment for falls, participant travel)	Tai chi $US1,080 (€952) Resistance $US1,186 (€1,046) Stretching $US1,155 (€1,019)	PD medication, physical therapy, medical treatment for falls and participant travel costs: Tai chi $US272 (€240) Resistance $US310 (€273) Stretching $US726 (€640)	Tai chi vs stretching (control): Cost per fall prevented ‐$US175 (‐€154) Cost per QALY gained ‐$US3,394 (‐€2,993) Resistance vs Tai Chi: Cost per fall prevented $US100 (€88) Cost per QALY gained $US1,236 (€1,090)
Munneke 2010 People with PD, both fallers and non‐fallers. Other exercise (ParkinsonNet therapists) vs Other exercise (standard therapists) Evaluated with cost analysis	Treatment from ParkinsonNet trained physiotherapists (n=343 to 350)* vs usual care (treatment from physiotherapists without specific PD training) (n=332‐340)*, both groups 24 weeks intervention period	Societal perspective, Euro, Price year not reported, but data collected 2005‐2007, During 24 weeks intervention	Health care costs (physiotherapy, medication, consultation, day‐hospital rehabilitation, admission to hospital, home‐care (paid services), informal care, costs due to lost productivity of the care‐partner).	Physiotherapy cost: ParkinsonNet group €297 Usual care group €310	Excluding physiotherapy: ParkinsonNet group €2,674 Usual care group €3,424	Not calculated
Exercise plus education trial
Morris 2017 People with PD, both fallers and non‐fallers. Gait, balance and functional training plus education vs control Evaluated with cost analysis	Exercise (strength training (lower limb and trunk), movement strategy training) and falls prevention education, 1 X week 60 mins supervised and 1 X week 60 mins independent practice for 6 weeks (n=67) vs Life Skills program (control) (n=66)	Health system perspective, Australian dollar, 2016, During 12 months follow‐up	Intervention costs (travel, home visits, therapist training, equipment). Life skills control intervention was considered as a placebo and therefore had no costs attributed to it. Medical costs associated with falling events (medical, medical ancillary, diagnostic and hospitalisation costs)	$A1,596 (€1,013)	Not reported	Not calculated as there was no difference between the groups

Study ID and comparison	Information related to adverse events
Exercise trials
Ashburn 2007 Gait, balance and functional training vs Control	No participants fell while performing the exercise program.
Canning 2015a Gait, balance and functional training vs Control	Two participants had non‐injurious falls during unsupervised exercise at home.
Chivers Seymour 2019 Gait, balance and functional training vs Control	No participants fell while performing the exercise program, and no adverse events were associated with the intervention. 0‐6 months hospitalisations: 9 PDSAFE exercise group participants (1 participant with 2 hospitalisations); 20 control group participants. 6‐12 months hospitalisations: 18 PDSAFE exercise group participants (2 participants with 2 hospitalisations); 21 control group participants (2 participants with 2 hospitalisations).
Gandolfi 2017 Gait, balance and functional training (virtual reality telerehabilitation) vs Gait, balance and functional training (balance training in a facility)	No adverse events were reported during the study.
Gandolfi 2019 Gait, balance and functional training (trunk‐specific exercises) vs Gait, balance and functional training (general exercises)	No adverse events or safety concerns were reported during the study.
Gao 2014 3D exercise (Tai Chi) vs Control	Not reported
Goodwin 2011 Gait, balance and functional training vs Control	No adverse events occurred during the exercise sessions.
Harro 2014 Gait, balance and functional training (cueing training) / Gait, balance and functional training (treadmill‐based gait training)	No adverse events during the intervention.
Li 2012 3D exercise (Tai Chi) / Resistance training vs Control	Tai‐chi (n=65): 3 in class events ‐ 2 falls, 1 muscle soreness or pain; 24 out of class events ‐ 19 falls, 4 low back pain, 1 ankle sprain. Functional strength training (n=65): 14 in class events ‐ 4 falls, 4 muscle soreness or pain, 3 dizziness or faintness, 3 symptoms of hypotension; 41 out of class events ‐ 31 falls, 3 chest pain, 1 hypotension, 4 low back pain, 2 ankle sprains. Stretching (n=65): 9 in‐class events ‐ 5 falls, 1 muscle soreness or pain, 2 dizziness or faintness, 1 symptoms of hypotension; 36 out of class events ‐ 26 falls, 2 chest pain, 2 hypotension, 5 low back pain, 1 ankle sprain. Nb ‐ out of class events are those that occurred during habitual activity or during an assessment. Participants did not perform any intervention outside the class.
Martin 2015 Gait, balance and functional training vs Control	Not reported
Mirelman 2016 Gait, balance and functional training (virtual reality treadmill training) vs Gait, balance and functional training (treadmill‐based gait training)	No serious adverse events during training. Adverse events other than those that occurred during intervention were recorded for both groups, but were not reported separately for the participants with Parkinson's disease.
Munneke 2010 Other exercise (ParkinsonNet therapists) / Other exercise (standard therapists)	None reported, though not collected systematically.
Paul 2014 Resistance training (muscle power training) vs Control	Power training (n=20): 1 exacerbation of pre‐existing low back pain, 1 pelvic fracture unrelated to the intervention, and 6 participants required modification to training loads due to transient pain, joint inflammation or illness. Control low intensity exercise (n=20): 2 participants had exacerbations of pre‐existing hernias, though this was not attributable to the low intensity exercise.
Pelosin 2017 Gait, balance and functional training (treadmill training at high frequency) vs Gait balance and functional training (treadmill training at intermediate frequency) vs Gait, balance and functional training (treadmill training at low frequency)	Not reported
Penko 2019 Gait, balance and functional training (Gait and cognitive training practised together) vs Gait, balance and functional training (Gait and cognitive training practised separately)	Not reported
Protas 2005 Gait, balance and functional training vs Control	Not reported
Ricciardi 2015 Gait, balance and functional training (best side therapy) / Gait, balance and functional training (worst side therapy) / Gait, balance and functional training (standard therapy)	Not reported
Sedaghati 2016 Gait, balance and functional training (with a balance pad) / Gait, balance and functional training (without a balance pad) vs Control	Not reported
Shen 2015 Gait, balance and functional training / Resistance training	No adverse events related to the intervention in either group.
Smania 2010 Gait, balance and functional training / Flexibility exercise	Not reported
Song 2018 Gait, balance and functional training vs Control	Adverse events were reported for the intervention group. Six participants ceased the stepping training: two ceased exercise due to it exacerbating pre‐existing lower back pain; two died; one sustained a knee injury from a fall unrelated to the intervention; one ceased for personal reasons. Additionally, one participant experienced a non‐injurious fall while undertaking the intervention and eight participants reported an increase in pre‐existing pain (e.g. lower back pain, knee pain, foot pain) but felt that the exacerbation was unrelated to the intervention.
Thaut 2019 Gait, balance and functional training (rhythmic auditory stimulation training throughout intervention period) vs Gait, balance and functional training (rhythmic auditory stimulation training with no training in middle 8 weeks of intervention period)	Participants who dropped out did so for reasons unrelated to adverse events.
Volpe 2014a Gait, balance and functional training (with proprioceptive stabiliser) / Gait, balance and functional training (without proprioceptive stabiliser)	No major adverse event related to the intervention.
Volpe 2014b Gait, balance and functional training (hydrotherapy) / Gait, balance and functional training (land‐based therapy)	Not reported
Wong‐Yu 2015 Gait, balance and functional training vs Control	No adverse events related to the intervention.
Medication trials
Chung 2010 Donepezil vs placebo	Donepezil (n=23): Eight participants (35%) reported 16 side effects (e.g. dehydration, gastrointestinal upset, headache, sleep disturbance, muscle cramps, orthostatic hypotension, weight loss). Placebo (n=23): Five participants (22%) reported 6 side effects (e.g. gastrointestinal upset, headache, sleep disturbance). These side effects were reported to be transient in most cases.
Henderson 2016 Rivastigmine vs placebo	Rivastigmine (n=64): 187 adverse events (excluding falls) Placebo (n=65): 122 adverse events (excluding falls) Adverse events included cardiac disorders, endocrine disorders, gastrointestinal disorders, general disorders and administration site disorders, immune system disorders, infections and infestations, injury, poisoning and procedural complications, investigations, metabolism and nutrition disorders, musculoskeletal and connective tissue disorders, neoplasms benign, malignant and unspecified, nervous system disorders, psychiatric disorders, renal and urinary disorders, respiratory, thoracic and mediastinal disorders, skin and subcutaneous tissue disorders, surgical medical procedures, vascular disorders. About one third of participants in the rivastigmine group complained of nausea. Most adverse events were categorised as mild and were considered to be unrelated to the intervention. There were 27 adverse events that were classified as serious; 14 in the rivastigmine group and 13 in the placebo group. Two of these events in the rivastigmine group were considered to be probably related to the rivastigmine. Twenty‐three participants in the rivastigmine group and 19 participants in the placebo group stopped taking the trial medication due to adverse events.
Li 2015a Rivastigmine vs placebo	Two participants withdrew due to adverse reactions, however details not provided.
Education trial
Ward 2004 Personalised education vs control (standardised printed information)	Not reported
Exercise plus education trials
Cattaneo 2019 Gait, balance and functional training plus education vs Control	Not reported
Morris 2015 Resistance training / Gait, balance and functional training (movement strategy training) vs Control	Functional strength training group (n=70): 25 occasions of new muscle soreness lasting > 24 hours Movement strategy training group (n=69): 11 occasions of new muscle soreness lasting > 24 hours, 1 fall and 2 occasions of dizziness during the intervention.
Morris 2017 Gait, balance and functional training vs Control	No adverse events related to the intervention.

Exercise (all types) compared with control (e.g. usual activities) for preventing falls in people with Parkinson's disease
Patient or population: People with Parkinson's disease Settings: Any Intervention: Exercise of all types Comparison: Control ‐ usual care or a non‐active intervention
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Certainty of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	Exercise (all types)
Rate of Falls (falls per person‐year) Follow‐up: range 2 weeks to 12 months	All exercise trials population		Rate ratio 0.74 (0.63 to 0.87)	1456 (12 RCTs)	⊕⊕⊕⊝ moderate^a	Overall, exercise probably reduces the number of falls by 26% (95% CI 37% reduction to 13% reduction).
	8250 falls per 1000 people	6105 falls per 1000 people (5198 to 7178)
Number of people who experienced one or more falls Follow‐up: range 2 weeks to 12 months	All exercise trials population		Risk ratio 0.90 (0.80 to 1.00)	932 (9 RCTs)	⊕⊕⊕⊝ moderate^a	Overall, exercise probably slightly reduces the number of people experiencing one or more falls by 10% (95% CI 20% reduction to no change).
	634 fallers per 1000 people	571 fallers per 1000 people (507 to 634)
Number of people sustaining one or more fall‐related fractures Follow‐up: range 20 weeks to 12 months	All exercise trials population		Risk ratio 0.57 (0.28 to 1.17)	989 (5 RCTs)	⊕⊝⊝⊝ very low^b	The evidence is of very low certainty, hence we are uncertain of the findings that exercise may make little or no difference in the number of people experiencing one or more fall‐related fractures.
	40 people with fracture per 1000	23 people with fracture per 1000 (11 to 47)
Quality of life immediately after the intervention assessed with various measures Follow‐up: range 8 weeks to 6 months A lower score indicates better quality of life	‐	The mean quality of life score in the intervention groups was 0.17 standard deviations lower (0.36 lower to 0.01 higher).		951 (5 RCTs)	⊕⊕⊝⊝ low^c	Overall, exercise may slightly improve quality of life by 2.6 points in the PDQ39 score (MD = 2.6 lower, 95% CI 5.5 lower to 0.2 higher). Of note is that the 95% CI includes the possibility of both increased and no change in quality of life. The SMD was converted back to MD using the PDQ39 scale (0‐100), using the pooled SD from the baseline scores of the largest included trial (Chivers Seymour 2019). The MID for the PDQ39 is about 1.6 (Peto 2001). SMD was calculated from 2 trials using the PDQ39, 1 trial using the PDQ8, 1 trial using the EQ‐5D visual analogue scale and 1 trial using the EQ‐5D index score.
Adverse events	Adverse events were reported inconsistently and often only for the exercise group. Three studies reported there were no adverse events related to the exercise intervention and one reported there were no falls during exercise. The remaining four studies reported minor adverse events such as muscle or joint soreness and non‐injurious falls.		Not estimable	1242 (8 RCTs)	⊕⊝⊝⊝ very low^d	The evidence is of very low certainty, hence we are uncertain whether exercise has an effect on adverse events.
Economic outcomes	We were unable to compare ICERs due to variations in the methods used, however reported ICERs suggest that exercise may be cost‐effective in preventing falls.		Not estimable	923 (4 RCTs)	⊕⊝⊝⊝ very low^d	The evidence is of very low certainty, hence we are uncertain whether exercise is a cost‐effective intervention for falls prevention.
The assumed risk* is the median control group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; ICERs: incremental cost‐effectiveness ratios; MD: mean difference; MID: minimally important difference; PDQ8: The Parkinson's Disease Questionnaire ‐ 8 items; PDQ39: The Parkinson's Disease Questionnaire ‐ 39 items; RCTs: randomised controlled trials; SD: standard deviation; SMD: standardised mean difference
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

Cholinesterase inhibitors compared with placebo medication for preventing falls in people with Parkinson's disease
Patient or population: People with Parkinson's disease Settings: Any Intervention: cholinesterase inhibitor medication (rivastigmine, donepezil) Comparison: placebo medication
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Certainty of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo	Cholinesterase inhibitor
Rate of falls (falls per person‐year) Follow‐up: range 12 weeks to 12 months	Cholinesterase inhibitor trial population		Rate ratio 0.50 (0.44 to 0.58)	229 (3 RCTs)	⊕⊕⊝⊝ low^a	Overall, cholinesterase inhibitors may reduce the number of falls by 50% (95% CI 42% reduction to 56% reduction).
	28,800 falls per 1000	14,400 falls per 1000 (12,672 to 16,704)
Number of people who experienced one or more falls Follow‐up: range 12 weeks to 12 months	Cholinesterase inhibitor trial population		Risk rato 1.01 (0.90 to 1.14)	230 (3 RCTs)	⊕⊝⊝⊝ verylow^b	The evidence is of very low certainty, hence we are uncertain of the finding that cholinesterase inhibitors make little or no difference to the number of people experiencing one or more falls.
	774 fallers per 1000	782 fallers per 1000 (697 to 882)
Number of people sustaining one or more fall‐related fractures Follow‐up: 12 weeks	Reported in one study, with no fractures in either group.		Not estimable	23 (1 RCT)	⊕⊝⊝⊝ verylow^c	The evidence is of very low certainty, hence we are uncertain whether cholinesterase inhibitors make little or no difference to the number of people sustaining one or more fall‐related fractures.
Quality of Life immediately after the intervention (EQ5D Thermometer, scale 0 to 100; and EQ5D Index Score, scale 0‐1, high score is better quality of life) Follow‐up: 8 months	The mean EQ5D thermometer score was 63 and the mean EQ5D Index Score was 0.66 in the placebo group.	In the cholinesterase inhibitor group the mean EQ5D Thermometer Score was 3 points higher (3.06 lower to 9.06 higher) and the mean EQ5D Index Score was 0.01 points lower (0.08 lower to 0.07 higher).		121 (1 RCT)	⊕⊝⊝⊝ very low^d	The evidence is of very low certainty, hence we are uncertain of the finding that cholinesterase inhibitors may make little or no difference to health‐related quality of life immediately after the intervention.
Rate of adverse events excluding falls (per person year) Follow‐up: range 12 weeks to 8 months	Cholinesterase inhibitor trial population		Rate ratio 1.60 (1.28 to 2.01)	175 (2 RCTs)	⊕⊕⊝⊝ low^e	Overall, cholinesterase inhibitors may increase the number of non fall‐related adverse events by 60% (95% CI 28% increase to 101% increase).
	1970 adverse events per 1000	3152 adverse events per 1000 (2,521 to 3,960)
Economic outcomes						No data reported for this outcome
The assumed risk* is the median control group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; MID: minimally important difference; RCTs: randomised controlled trials.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Rate of falls	12	1456	Rate Ratio (IV, Random, 95% CI)	0.74 [0.63, 0.87]
1.2 Rate of falls subgrouped by ProFaNE exercise categories	12	1456	Rate Ratio (IV, Random, 95% CI)	0.74 [0.63, 0.87]
1.2.1 Gait, balance and functional training vs Control	9	1146	Rate Ratio (IV, Random, 95% CI)	0.80 [0.67, 0.95]
1.2.2 Resistance training vs control	2	136	Rate Ratio (IV, Random, 95% CI)	0.72 [0.55, 0.94]
1.2.3 3D exercise (Tai Chi) vs Control	2	174	Rate Ratio (IV, Random, 95% CI)	0.41 [0.23, 0.72]
1.3 Rate of falls ‐ subgrouped by % supervision (100% supervision vs <100% supervision)	12		Rate Ratio (IV, Random, 95% CI)	Subtotals only
1.3.1 100% supervision	5	373	Rate Ratio (IV, Random, 95% CI)	0.56 [0.41, 0.77]
1.3.2 < 100% supervision	7	1083	Rate Ratio (IV, Random, 95% CI)	0.85 [0.75, 0.97]
1.4 Rate of falls ‐ subgrouped by baseline fall risk (increased fall risk vs fall risk not specified)	12		Rate Ratio (IV, Random, 95% CI)	Subtotals only
1.4.1 Higher fall risk participants	7	1082	Rate Ratio (IV, Random, 95% CI)	0.73 [0.59, 0.91]
1.4.2 Unspecified fall risk participants	5	374	Rate Ratio (IV, Random, 95% CI)	0.71 [0.56, 0.90]
1.5 Rate of falls ‐ pooled disease severity subgroup analyses_UPDRS	2		Rate Ratio (IV, Random, 95% CI)	Subtotals only
1.5.1 Higher disease severity participants	2		Rate Ratio (IV, Random, 95% CI)	1.47 [1.11, 1.94]
1.5.2 Lower disease severity participants	2		Rate Ratio (IV, Random, 95% CI)	0.65 [0.39, 1.08]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Number of fallers	9	932	Risk Ratio (IV, Random, 95% CI)	0.90 [0.80, 1.00]
2.2 Number of fallers subgrouped by ProFaNE exercise categories	9	932	Risk Ratio (IV, Random, 95% CI)	0.90 [0.80, 1.00]
2.2.1 Gait, balance and functional training vs Control	6	622	Risk Ratio (IV, Random, 95% CI)	0.92 [0.81, 1.04]
2.2.2 Resistance training vs control	2	136	Risk Ratio (IV, Random, 95% CI)	0.87 [0.43, 1.74]
2.2.3 3D exercise (Tai Chi) vs control	2	174	Risk Ratio (IV, Random, 95% CI)	0.59 [0.36, 0.95]
2.3 Number of fallers ‐ subgrouped by % supervision (100% supervision vs <100% supervision)	9		Risk Ratio (IV, Random, 95% CI)	Subtotals only
2.3.1 100% supervision	4	328	Risk Ratio (IV, Random, 95% CI)	0.75 [0.53, 1.06]
2.3.2 < 100% supervision	5	604	Risk Ratio (IV, Random, 95% CI)	0.92 [0.82, 1.04]
2.4 Number of fallers ‐ subgrouped by baseline fall risk (increased fall risk vs fall risk not specified)	9		Risk Ratio (IV, Random, 95% CI)	Subtotals only
2.4.1 Higher fall risk participants	5	576	Risk Ratio (IV, Random, 95% CI)	0.89 [0.76, 1.04]
2.4.2 Unspecified fall risk participants	4	356	Risk Ratio (IV, Random, 95% CI)	0.86 [0.67, 1.11]
2.5 Number of fallers ‐ pooled disease severity subgroup analyses	2		Risk Ratio (IV, Random, 95% CI)	Subtotals only
2.5.1 Higher disease severity participants	2	139	Risk Ratio (IV, Random, 95% CI)	1.19 [1.00, 1.41]
2.5.2 lower disease severity participants	2	218	Risk Ratio (IV, Random, 95% CI)	0.78 [0.62, 0.98]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
4.1 Health‐related quality of life ‐ combined measures post intervention	5	951	Std. Mean Difference (IV, Random, 95% CI)	‐0.17 [‐0.36, 0.01]
4.2 Health‐related quality of life ‐ combined measures follow‐up	3	429	Std. Mean Difference (IV, Random, 95% CI)	‐0.27 [‐0.46, ‐0.08]

Outcome or subgroup title	No. of studies	Statistical method	Effect size
6.1 Number of fallers, different types of exercise compared	4	Risk Ratio (IV, Fixed, 95% CI)	Totals not selected
6.1.1 Gait, balance and functional training vs gait, balance and functional training	2	Risk Ratio (IV, Fixed, 95% CI)	Totals not selected
6.1.2 Gait, balance and functional training vs resistance training	1	Risk Ratio (IV, Fixed, 95% CI)	Totals not selected
6.1.3 3D exercise (Tai Chi) vs resistance training	1	Risk Ratio (IV, Fixed, 95% CI)	Totals not selected

Health education compared with usual care for preventing falls in people with Parkinson's disease
Patient or population: People with Parkinson's disease Settings: Any Intervention: Education about falls prevention Comparison: Usual care
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Certainty of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Usual care	Health education
Rate of falls (falls per person‐year)						No data reported for this outcome
Number of people who experienced one or more falls Follow‐up: 12 months	All exercise trials population*		Risk ratio 10.89 (1.26 to 94.03)	53 (1 RCT)	⊕⊝⊝⊝ very low^a	The evidence is of very low certainty, hence we are uncertain of the finding that health education increases the number of people who experience one or more falls.
	634 fallers per 1000 people	6,911 per 1000 (824 to 59,596)
Number of people sustaining one or more fall‐related fractures						No data reported for this outcome
Quality of life						No data reported for this outcome
Adverse events						No data reported for this outcome
Economic outcomes						No data reported for this outcome
The assumed risk* is the median control group risk across exercise versus control studies, as there were no data to calculate the illustrative risk in the health education trial. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RCT: randomised controlled trial
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

Exercise (all types) plus education for falls prevention compared with control (e.g. usual activities) for preventing falls in people with Parkinson's disease
Patient or population: People with Parkinson's disease Settings: Any Intervention: Exercise of all types plus fall‐prevention education Comparison: Control ‐ usual care or a non‐active intervention
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Certainty of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	Exercise plus education
Rate of Falls (falls per person‐year) Follow‐up: 12 months	Exercise plus education trials population		Rate ratio 0.46 (0.12 to 1.85)	320 (2 RCTs)	⊕⊝⊝⊝ very low^a	The evidence is of very low certainty, hence we are uncertain of the finding that exercise plus education makes little or no difference to the number of falls.
	16,400 falls per 1000 people	7,544 per 1000 (1968 to 30,340)
Number of people who experienced one or more falls Follow‐up: range 6 months to 12 months	Exercise plus education trials population		Risk Ratio 0.89 (0.75 to 1.07)	352 (3 RCTs)	⊕⊕⊝⊝ low^b	Overall, exercise plus education may make little or no difference to the number of people experiencing one or more falls (11% reduction (95% CI 25% reduction to 7% increase)).
	672 per 1000	598 per 1000 (504 to 719)
Number of people sustaining one or more fall‐related fractures Follow‐up: 12 months	Exercise plus education trials population		Risk ratio 1.45 (0.40 to 5.32)	320 (2 RCTs)	⊕⊝⊝⊝ very low^c	The evidence is of very low certainty, hence we are uncertain of the finding that exercise plus education makes little or no difference to the number of people experiencing one or more fall‐related fractures.
	25 per 1000	36 per 1000 (10 to 133)
Quality of life immediately after the intervention assessed with the PDQ39 (range 0 to 100) Follow‐up: 6 weeks A lower score indicates better quality of life	‐	The mean PDQ39 in the intervention groups was 0.05 points higher (3.12 lower to 3.23 higher)		305 (2 RCTs)	⊕⊝⊝⊝ very low^d	The evidence is of very low certainty, hence we are uncertain of the finding that exercise plus education makes little or no difference to health‐related quality of life immediately after the intervention.
Adverse events	Adverse events related to the exercise intervention only were reported. One study reported there were no adverse events, while the other reported minor adverse events such as muscle soreness and a fall while exercising.		Not estimable	343 (2 RCTs)	⊕⊝⊝⊝ very low^e	The evidence is of very low certainty, hence we are uncertain whether exercise plus education has an effect on adverse events.
Economic Outcomes	Costs per fall prevented were not calculated as there was no reduction in falls in this study		Not estimable	133 (1 RCT)	⊕⊝⊝⊝ very low^f	The evidence is of very low certainty, hence we are uncertain whether exercise plus education is a cost‐effective intervention for falls prevention.
The assumed risk* the median control group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; MID: minimally important difference; PDQ39: The Parkinson's Disease Questionnaire ‐ 39 items; RCTs: randomised controlled trials
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

Study ID and comparison	Subgroup definition, number of participants (n)	Intervention lower severity group: falls per person year	Intervention higher severity group: falls per person year	Intervention lower severity group: number (%) of fallers	Intervention higher severity group: number (%) of fallers	Control lower severity group: falls per person year	Control higher severity group: falls per person year	Control lower severity group: number (%) of fallers	Control higher severity group: number (%) of fallers	Length of falls monitoring
Ashburn 2007 Gait, balance and functional training vs Control	Lower disease severity: Hoehn and Yahr stages 2 and 3, n = 96 Higher disease severity: Hoehn and Yahr stage 4, n = 30	NA	NA	31 (66%)	15 (94%)	NA	NA	37 (76%)	12 (86%)	6 months
Canning 2015a Gait, balance and functional training vs Control	Lower disease severity: UPDRS motor score ≤ 26, n = 122 Higher disease severity: UPDRS motor score ≥ 27, n = 109	ND	ND	ND	ND	ND	ND	ND	ND	6 months
Chivers Seymour 2019 (data reported in Ashburn 2019) Gait, balance and functional training vs Control	Lower disease severity: includes both the low disease severity subgroup ‐ MDS‐UPDRS motor score ≤ 22, n = 152 and moderate disease severity subgroup ‐ MDS‐UPDRS motor score 23 ‐ 28, n = 155 Higher disease severity: MDS‐UPDRS motor score ≥ 39, n = 152	ND	ND	NA	NA	ND	ND	NA	NA	6 months

Sensitivity analysis	Pooled impact of intervention on fall rate, Rate ratio, 95% CI
Exercise trials vs control
Primary analysis, all trials, random effects meta‐analysis	0.74, 0.63 to 0.87; participants = 1456; trials = 12
Sensitivity analysis 1, removing trials with high risk of bias in any item	0.74, 0.61 to 0.90; participants = 1,245; trials = 9
Sensitivity analysis 2, removing trials with unclear or high risk of bias on random sequence generation	0.90, 0.76 to 1.05; participants = 995; trials = 7
Sensitivity analysis 3, removing trials with unclear or high risk of bias on allocation concealment	0.80, 0.70 to 0.91; participants = 1299; trials = 8
Sensitivity analysis 4, removing trials with unclear or high risk of bias on assessor blinding	0.92, 0.73 to 1.16; participants = 692; trials = 2
Sensitivity analysis 5, removing trials with unclear or high risk of bias on incomplete outcome data	0.77, 0.65 to 0.92; participants = 1260; trials = 11
Sensitivity analysis 6, removing trials with less than three months falls monitoring	0.79, 0.68 to 0.92; participants = 1268; trials = 9
Sensitivity analysis 8, all exercise trials, fixed effects meta‐analysis	0.79, 0.71 to 0.88; participants = 1456; trials = 12
Primary analysis, subgrouped by exercise type Gait, balance and functional training Resistance training 3D exercise	0.80, 0.67 to 0.95; participants = 1146; trials = 9 0.72, 0.55 to 0.94; participants = 137; trials = 2 0.41, 0.23 to 0.72; participants = 174; trials = 2 Test for subgroup differences Chi² = 4.92, df = 2 (P = 0.09), I² = 59.3%
Sensitivity analysis 10, classification of interventions that included functional strength training from resistance training to gait, balance and functional training Gait, balance and functional training Resistance training 3D exercise	0.78, 0.68 to 0.91; participants = 1244; trials = 10 0.84, 0.28 to 2.53; participants = 38; trials = 1 0.41, 0.23 to 0.72; participants = 174; trials = 2 Test for subgroup differences Chi² = 4.8, df = 2 (P = 0.09), I² = 58.3%
Medication trials ‐ cholinesterase inhibitor vs placebo
Primary analysis, all trials, fixed effects meta‐analysis	0.50, 0.44 to 0.58; participants = 229; trials = 3
Sensitivity analysis 1, removing trials with high risk of bias in any item	0.43, 0.32 to 0.56; participants = 81; trials = 1
Sensitivity analysis 2, removing trials with unclear or high risk of bias on random sequence generation	0.60, 0.38 to 0.96; participants = 129; trials = 1
Sensitivity analysis 3, removing trials with unclear or high risk of bias on allocation concealment	0.60, 0.38 to 0.96; participants = 129; trials = 1
Sensitivity analysis 5, removing trials with unclear or high risk of bias on incomplete outcome data	0.60, 0.38 to 0.96; participants = 129; trials = 1
Sensitivity analysis 9, all cholinesterase inhibitor trials, random effects meta‐analysis	0.50, 0.43 to 0.58; participants = 229; trials = 3
Exercise plus education trials vs control
Primary analysis, all trials, random effects meta‐analysis	0.46, 0.12 to 1.85; participants = 320; trials = 2
Sensitivity analysis 1, removing trials with high risk of bias in any item	1.58, 0.74 to 3.40; participants = 124; trials = 1
Sensitivity analysis 4, removing trials with unclear or high risk of bias on assessor blinding	0.24, 0.10 to 0.61; participants = 196; trials = 1
Sensitivity analysis 5, removing trials with unclear or high risk of bias on incomplete outcome data	1.58, 0.74 to 3.40; participants = 124; trials = 1
Sensitivity analysis 7, removing the comparison responsible for the high level of heterogeneity (Morris 2017)	0.24, 0.10 to 0.61; participants = 196; trials = 1
Sensitivity analysis 8, all exercise plus education trials, fixed effects meta‐analysis	0.54, 0.33 to 0.89; participants = 320; trials = 2

Sensitivity analysis	Pooled impact of intervention on risk of falling, Risk ratio, 95% CI
Exercise trials vs control
Primary analysis, all exercise trials, random effects meta‐analysis	0.90, 0.80 to 1.00; participants = 932; trials = 9
Sensitivity analysis 1, removing trials with high risk of bias in any item	0.87, 0.75 to 1.02; participants = 721; trials = 6
Sensitivity analysis 2, removing trials with unclear or high risk of bias on random sequence generation	0.89, 0.76 to 1.04; participants = 516; trials = 5
Sensitivity analysis 3, removing trials with unclear or high risk of bias on allocation concealment	0.91, 0.81 to 1.03; participants = 838; trials = 7
Sensitivity analysis 4, removing trials with unclear or high risk of bias on assessor blinding	0.93, 0.78 to 1.11; participants = 231; trials = 1
Sensitivity analysis 5, removing trials with unclear or high risk of bias on incomplete outcome data	0.89, 0.79 to 1.00; participants = 736; trials = 8
Sensitivity analysis 6, removing trials with less than three months falls monitoring	0.89, 0.77 to 1.02; participants = 789; trials = 7
Sensitivity analysis 8, all exercise trials, fixed effects meta‐analysis	0.90, 0.80 to 1.00; participants = 932; trials = 9
Primary analysis, subgrouped by exercise type Gait, balance and functional training Resistance training 3D exercise	0.92, 0.81 to 1.04; participants = 622; trials = 6 0.87, 0.43 to 1.74; participants = 136; trials = 2 0.59, 0.36 to 0.95; participants = 174; trials = 2 Test for subgroup differences Chi² = 3.14, df = 2 (P = 0.21), I² = 36.2%
Sensitivity analysis 10, classification of interventions that included functional strength training from resistance training to gait, balance and functional training Gait, balance and functional training Resistance training 3D exercise	0.93, 0.83 to 1.05; participants = 720; trials = 7 0.58, 0.30 to 1.13; participants = 38; trials = 1 0.59, 0.36 to 0.95; participants = 174; trials = 2 Test for subgroup differences Chi² = 5.02, df = 2 (P = 0.08), I² = 60.1%
Medication trials ‐ cholinesterase inhibitor vs placebo
Primary analysis, all trials, fixed effects meta‐analysis	1.01, 0.90 to 1.14; participants = 230; trials = 3
Sensitivity analysis 1, removing trials with high risk of bias in any item	0.31, 0.12 to 0.78; participants = 81; trials = 1
Sensitivity analysis 2, removing trials with unclear or high risk of bias on random sequence generation	1.00, 0.87 to 1.15; participants = 130; trials = 1
Sensitivity analysis 3, removing trials with unclear or high risk of bias on allocation concealment	1.00, 0.87 to 1.15; participants = 130; trials = 1
Sensitivity analysis 5, removing trials with unclear or high risk of bias on incomplete outcome data	1.03, 0.92 to 1.16; participants = 149; trials = 2
Sensitivity analysis 7, removing the comparison responsible for the high level of heterogeneity (Li 2015a)	1.03, 0.92 to 1.16; participants = 149; trials = 2
Sensitivity analysis 9, all cholinesterase inhibitor trials, random effects meta‐analysis	0.95, 0.70 to 1.28; participants = 230; trials = 3
Exercise plus education trials vs control
Primary analysis, all trials, random effects meta‐analysis	0.89, 0.75 to 1.07; participants = 352; trials = 3
Sensitivity analysis 1, removing trials with high risk of bias in any item	0.84, 0.65 to 1.08; participants = 156; trials = 2
Sensitivity analysis 3, removing trials with unclear or high risk of bias on allocation concealment	0.90, 0.75 to 1.08; participants = 320, trials = 2
Sensitivity analysis 4, removing trials with unclear or high risk of bias on assessor blinding	0.93, 0.73 to 1.19; participants = 228, trials = 2
Sensitivity analysis 8, all exercise plus education trials, fixed effects meta‐analysis	0.89, 0.75 to 1.07; participants = 352; trials = 3

Outcome or subgroup title	No. of studies	Statistical method	Effect size
5.1 Rate of falls, different types of exercise compared	14	Rate Ratio (IV, Fixed, 95% CI)	Totals not selected
5.1.1 Gait, balance and functional training vs gait, balance and functional training	10	Rate Ratio (IV, Fixed, 95% CI)	Totals not selected
5.1.2 Gait, balance and functional training vs resistance training	1	Rate Ratio (IV, Fixed, 95% CI)	Totals not selected
5.1.3 Gait, balance and functional training vs flexibility	1	Rate Ratio (IV, Fixed, 95% CI)	Totals not selected
5.1.4 3D exercise (Tai Chi) vs resistance training	1	Rate Ratio (IV, Fixed, 95% CI)	Totals not selected
5.1.5 Other exercise vs Other exercise	1	Rate Ratio (IV, Fixed, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	Statistical method	Effect size
7.1 Quality of life ‐ combined measures post intervention, different types of exercise compared	8	Std. Mean Difference (IV, Fixed, 95% CI)	Totals not selected
7.1.1 Gait, balance and functional training vs Gait, balance and functional training	6	Std. Mean Difference (IV, Fixed, 95% CI)	Totals not selected
7.1.2 3D exercise (Tai Chi) vs Resistance exercise	1	Std. Mean Difference (IV, Fixed, 95% CI)	Totals not selected
7.1.3 Other exercise vs Other exercise	1	Std. Mean Difference (IV, Fixed, 95% CI)	Totals not selected
7.2 Quality of life ‐ combined measures follow‐up, different types of exercise compared	5	Std. Mean Difference (IV, Fixed, 95% CI)	Totals not selected
7.2.1 Functional gait, balance and strength training vs Functional gait, balance and strength training	5	Std. Mean Difference (IV, Fixed, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
8.1 Rate of falls	3	248	Rate Ratio (IV, Fixed, 95% CI)	0.50 [0.44, 0.58]
8.2 Rate of falls ‐ subgrouped by medication	3	248	Rate Ratio (IV, Random, 95% CI)	0.50 [0.43, 0.58]
8.2.1 Rivastigmine vs placebo	2	210	Rate Ratio (IV, Random, 95% CI)	0.48 [0.35, 0.66]
8.2.2 Donepezil vs placebo	1	38	Rate Ratio (IV, Random, 95% CI)	0.52 [0.44, 0.62]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
9.1 Number of fallers	3	249	Risk Ratio (IV, Fixed, 95% CI)	1.01 [0.90, 1.14]
9.2 Number of fallers ‐ subgrouped by medication	3		Risk Ratio (IV, Random, 95% CI)	0.95 [0.70, 1.28]
9.2.1 Rivastigmine vs placebo	2		Risk Ratio (IV, Random, 95% CI)	0.61 [0.20, 1.90]
9.2.2 Donepezil vs placebo	1		Risk Ratio (IV, Random, 95% CI)	1.13 [0.90, 1.40]

Outcome or subgroup title	No. of studies	Statistical method	Effect size
10.1 Quality of life EQ5D thermometer post intervention	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
10.1.1 Rivastigmine vs placebo	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
10.2 Quality of life EQ5D Index Score post intervention	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
10.2.1 Rivastigmine vs placebo	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected

PERMALINK

Interventions for preventing falls in Parkinson's disease

Natalie E Allen

Colleen G Canning

Lorena Rosa S Almeida

Bastiaan R Bloem

Samyra HJ Keus

Niklas Löfgren

Alice Nieuwboer

Geert SAF Verheyden

Tiê P Yamato

Catherine Sherrington

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Background

Description of the condition

Description of the intervention

How the intervention might work

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Types of interventions

3. Exercise categories (based on ProFaNE): definition and application.

Types of outcome measures

Primary outcomes

Secondary outcomes

Timing of outcome measurement

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

Selection of studies

Data extraction and management

Assessment of risk of bias in included studies

4. Risk of bias assessment tool.

Measures of treatment effect

Unit of analysis issues

Dealing with missing data

Assessment of heterogeneity

Assessment of reporting biases

Data synthesis

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

Summary of findings and assessment of the certainty of the evidence

Results

Description of studies

Results of the search

1.

Included studies

Trial design

Trial size

Trial setting

Participants

Interventions

5. Features of exercise interventions.

Outcomes

6. Source of data for generic inverse variance analysis (see footnotes for explanations of codes).

7. Raw data for rate ratios and risk ratios.

8. Baseline fall data.

9. Raw data for quality of life.

10. Studies reporting an economic analysis related to the cost of the intervention and/or fall outcomes.

11. Adverse events.

Excluded studies

Ongoing studies

Risk of bias in included studies

2.

3.

Allocation

Blinding

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
16.1 Health‐related quality of life ‐ Parkinson's Disease Questionnaire (PDQ39) post intervention	2	305	Mean Difference (IV, Random, 95% CI)	0.05 [‐3.12, 3.23]
16.2 Health‐related quality of life ‐ Parkinson's Disease Questionnaire (PDQ39) at follow‐up	2	299	Mean Difference (IV, Random, 95% CI)	‐2.25 [‐5.45, 0.96]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
17.1 Rate of falls	1		Rate Ratio (IV, Fixed, 95% CI)	Totals not selected
17.1.1 Gait, balance and functional training plus education vs resistance training plus education	1		Rate Ratio (IV, Fixed, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
18.1 Number of fallers	1		Risk Ratio (IV, Fixed, 95% CI)	Totals not selected
18.1.1 Gait, balance and functional training plus education vs resistance training plus education	1		Risk Ratio (IV, Fixed, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
19.1 Number of people sustaining one or more fall‐related fractures	1		Risk Ratio (IV, Fixed, 95% CI)	Totals not selected
19.1.1 Gait, balance and functional training plus education vs resistance training plus education	1		Risk Ratio (IV, Fixed, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	Statistical method	Effect size
20.1 Health‐related quality of life ‐ Parkinson's Disease Questionnaire (PDQ39) post intervention	1	Std. Mean Difference (IV, Fixed, 95% CI)	Totals not selected
20.1.1 Gait, balance and functional training plus education vs resistance training plus education	1	Std. Mean Difference (IV, Fixed, 95% CI)	Totals not selected
20.2 Health‐related quality of life ‐ Parkinson's Disease Questionnaire (PDQ39) at follow‐up	1	Std. Mean Difference (IV, Fixed, 95% CI)	Totals not selected
20.2.1 Gait, balance and functional training plus education vs resistance training plus education	1	Std. Mean Difference (IV, Fixed, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
21.1 Rate of falls ‐ exercise vs control	9	1245	Rate Ratio (IV, Random, 95% CI)	0.74 [0.61, 0.90]
21.2 Number of fallers ‐ exercise vs control	6	721	Risk Ratio (IV, Random, 95% CI)	0.87 [0.75, 1.02]
21.3 Rate of falls ‐ cholinesterase inhibitor vs placebo	1	81	Rate Ratio (IV, Fixed, 95% CI)	0.43 [0.32, 0.56]
21.3.1 Rivastigmine vs placebo	1	81	Rate Ratio (IV, Fixed, 95% CI)	0.43 [0.32, 0.56]
21.4 Number of fallers ‐ cholinesterase inhibitor vs placebo	1	81	Risk Ratio (IV, Fixed, 95% CI)	0.31 [0.12, 0.78]
21.4.1 Rivastigmine vs placebo	1	81	Risk Ratio (IV, Fixed, 95% CI)	0.31 [0.12, 0.78]
21.5 Rate of falls ‐ exercise and education vs control	1	124	Rate Ratio (IV, Random, 95% CI)	1.58 [0.74, 3.40]
21.6 Number of fallers ‐ exercise and education vs control	2	156	Risk Ratio (IV, Random, 95% CI)	0.84 [0.65, 1.08]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
22.1 Rate of falls ‐ exercise vs control	7	995	Rate Ratio (IV, Random, 95% CI)	0.90 [0.76, 1.05]
22.2 Number of fallers ‐ exercise vs control	5	516	Risk Ratio (IV, Random, 95% CI)	0.89 [0.76, 1.04]
22.3 Rate of falls ‐ cholinesterase inhibitor vs placebo	1	129	Rate Ratio (IV, Fixed, 95% CI)	0.60 [0.38, 0.96]
22.3.1 Rivastigmine vs placebo	1	129	Rate Ratio (IV, Fixed, 95% CI)	0.60 [0.38, 0.96]
22.4 Number of fallers ‐ cholinesterase inhibitor vs placebo	1	130	Risk Ratio (IV, Fixed, 95% CI)	1.00 [0.87, 1.15]
22.4.1 Rivastigmine vs placebo	1	130	Risk Ratio (IV, Fixed, 95% CI)	1.00 [0.87, 1.15]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
23.1 Rate of falls ‐ exercise vs control	8	1299	Rate Ratio (IV, Random, 95% CI)	0.80 [0.70, 0.91]
23.2 Number of fallers ‐ exercise vs control	7	838	Risk Ratio (IV, Random, 95% CI)	0.91 [0.81, 1.03]
23.3 Rate of falls ‐ cholinesterase inhibitor vs placebo	1	129	Rate Ratio (IV, Fixed, 95% CI)	0.60 [0.38, 0.96]
23.3.1 Rivastigmine vs placebo	1	129	Rate Ratio (IV, Fixed, 95% CI)	0.60 [0.38, 0.96]
23.4 Number of fallers ‐ cholinesterase inhibitor vs placebo	1	130	Risk Ratio (IV, Fixed, 95% CI)	1.00 [0.87, 1.15]
23.4.1 Rivastigmine vs placebo	1	130	Risk Ratio (IV, Fixed, 95% CI)	1.00 [0.87, 1.15]
23.5 Number of fallers ‐ exercise and education vs control	2	320	Risk Ratio (IV, Random, 95% CI)	0.90 [0.75, 1.08]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
24.1 Rate of falls ‐ exercise vs control	2	692	Rate Ratio (IV, Random, 95% CI)	0.92 [0.73, 1.16]
24.2 Number of fallers ‐ exercise vs control	1	231	Risk Ratio (IV, Random, 95% CI)	0.93 [0.78, 1.11]
24.3 Rate of falls ‐ exercise and education vs control	1	196	Rate Ratio (IV, Random, 95% CI)	0.24 [0.10, 0.61]
24.4 Number of fallers ‐ exercise and education vs control	2	228	Risk Ratio (IV, Random, 95% CI)	0.93 [0.73, 1.19]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
25.1 Rate of falls ‐ exercise vs control	11	1260	Rate Ratio (IV, Random, 95% CI)	0.77 [0.65, 0.92]
25.2 Number of fallers ‐ exercise vs control	8	736	Risk Ratio (IV, Random, 95% CI)	0.89 [0.79, 1.00]
25.3 Rate of falls ‐ cholinesterase inhibitor vs placebo	1	129	Rate Ratio (IV, Fixed, 95% CI)	0.60 [0.38, 0.96]
25.3.1 Rivastigmine vs placebo	1	129	Rate Ratio (IV, Fixed, 95% CI)	0.60 [0.38, 0.96]
25.4 Number of fallers ‐ cholinesterase inhibitor vs placebo	2	168	Risk Ratio (IV, Fixed, 95% CI)	1.03 [0.92, 1.16]
25.4.1 Rivastigmine vs placebo	1	130	Risk Ratio (IV, Fixed, 95% CI)	1.00 [0.87, 1.15]
25.4.2 Donepezil vs placebo	1	38	Risk Ratio (IV, Fixed, 95% CI)	1.13 [0.90, 1.40]
25.5 Rate of falls ‐ exercise and education vs control	1	124	Rate Ratio (IV, Random, 95% CI)	1.58 [0.74, 3.40]