A post-trial survey to assess the impact of dissemination of results and unmasking on participants in a 13-year randomised controlled trial on age-related cataract

Abstract

BackgroundThe Italian-American Clinical Trial of Nutritional Supplements and Age-Related Cataract was designed to assess the impact of a multivitamin-mineral supplement on age-related cataract. Trial results showed evidence of a beneficial effect of the supplement on all types of cataract combined, opposite effects on two of the three types of cataract (beneficial for nuclear opacities and harmful for posterior sub-capsular opacities) and no statistically significant effect on cortical opacities. No treatment recommendations were made. A post-trial survey was conducted on 817 surviving elderly participants to assess their satisfaction, their understanding of treatment assignment to supplement or placebo and the success of masking.MethodsTrial results were communicated by letter and the level of satisfaction and of understanding of the results was assessed by a questionnaire. Participants were offered the option of being unmasked: a second questionnaire was administered to this subset to assess their understanding of the randomisation process and the success of masking.Results610 participants (74.7%) responded to the survey:94.6% thought the description of the results was "very clear" or "quite clear", 5.4% "not clear" or "do not know"; 89.8% considered the results "very interesting" or "quite interesting", 10.2% "not interesting" or "do not know"; 60.3% expressed "satisfaction", 17.2% "both satisfaction and concern", 2.6% "concern", 19.9% "indifference" or "do not know".480 participants (78.7%) accepted the offer to be unmasked to their treatment assignment: 395 (82.3%) recalled/understood the possibility of assignment to vitamins or placebo, 85 (17.7%) did not. 68 participants (17.2%) thought they had taken vitamins (79.4% were correct; p = 0.0006), 47 (11.9%) thought they had taken placebo (59.6% were correct; p = 0.46) and 280 (70.9%) declared they did not know.ConclusionsThe results were made difficult to explain to study participants by the qualitatively different effect of treatment on the two most visually significant types of cataract. Although the study did not lead to a recommendation to use the dietary supplement, the vast majority of participants reported satisfaction after they received the results but almost 20% of the participants expressed some concern. Masking to treatment assignment was successful in the majority of participants.

Providing trial results to participants in phase III pragmatic effectiveness RCTs: a scoping review

“…A questionnaire survey of participants’ reactions to receiving the results leaflet was conducted. Aggregate Not specified Locock 2011 [ 26 ] Personal experiences of taking part in clinical trials—a qualitative study Trial participants 42 27 female; 15 male 38-84 years N/A UK To investigate people’s experiences of and attitudes to participation in clinical trials interviews N/A N/A Williams 2011 [ 27 ] The Italian-American Clinical Trial of Nutritional supplements and Age-Related Cataract (CTNS) Trial participants 610 46.7% female; 53.3% male Mean age 80.5 Not specified Italy To determine whether participants were satisfied with the trial results. Survey Aggregate and individual After publication Darbyshire 2012 [ 28 ] Disseminating results to clinical trial participants: a qualitative review of patient understanding in a post-trial population Trial participants 40 Not specified Not specified Secondary care UK To identify the most appropriate format for results dissemination to maximise understanding of trial results.…”

“… Postal Informed by the findings of the focus groups and input from other stakeholders, a results leaflet for participants was produced, and an integrated process of feedback and support was developed. Not reported Not specified Not specified Locock 2011 [ 26 ] N/A N/A N/A N/A Not reported N/A N/A Williams 2011 [ 27 ] Aggregate and individual The frequency figures were used to demonstrate the effect of treatment. The letter indicated that, because of the qualitatively different effect of treatment on the different types of cataract, the investigators could not recommend regular use of the supplement for the prevention of cataract.…”

“…One study mentioned that dissemination of trial results may facilitate trial retention [ 26 ] and another cited raising public awareness of the importance of research [ 36 ]. The potential to motivate others to participate in future research was also identified as a benefit of disseminating trial results [ 2 , 25 , 27 ].…”

Unblinding following trial participation: Qualitative study of participants’ perspectives

“…In contrast to other studies of participants' views of unblinding [3,5], our interviews were not linked to an explicit offer to unblind participants as to their treatment allocation. As a result, the women in this study were not discussing their actual experiences of being unblinded (or choosing not to be), but rather the possibility of finding out their treatment allocation more generally.…”

“…The limited evidence to date suggests that trial participants generally want to be unblinded to treatment allocation on trial completion, and that few patients report concerns at finding out to which trial arm they were allocated [3,5]. But in trials where analysis reveals adverse outcomes for some participant groups, the possible unblinding of participants may be less straightforward.…”