Summary of findings 2. Summary of findings for cholinesterase inhibitors compared to placebo.

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)	⊕⊕⊝⊝ lowa	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)	⊕⊝⊝⊝ verylowb	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)	⊕⊝⊝⊝ verylowc	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 lowd	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)	⊕⊕⊝⊝ lowe	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.

^aDowngraded by two levels for imprecision due to the relatively small sample size. There was no downgrading for risk of bias as the sensitivity analyses to remove trials at high risk of bias in any item, or high/unclear risk of bias in any domain, made little difference to the result (Table 3).

^bDowngraded by one level due to risk of bias as results changed when removing the two trials with a high risk of bias in any item (Henderson 2016, Chung 2010) (Table 4). Downgraded an additional two levels due to imprecision because of the relatively small sample size. There was no downgrading for inconsistency as results were essentially unchanged with removal of the comparison responsible for the high heterogeneity (Li 2015a) (Table 4).

^cDowngraded by two levels for imprecision due to the very small sample size. Downgraded a further one level as only one of the three studies included in the review for this comparison contributed to the outcome.

^dDowngraded by two levels for imprecision due to the relatively small sample size. Downgraded a further one level as only one of the three studies included in the review for this comparison contributed to the outcome.

^eDowngraded by two levels for imprecision due to the relatively small sample size.