Reducing attrition within clinical trials: The communication of retention and withdrawal within patient information leaflets.

BACKGROUND: The recruitment and retention of patients are significant methodological challenges for trials. Whilst research has focussed on recruitment, the failure to retain recruited patients and collect outcome data can lead to additional problems and potentially biased results. Research to identify effective retention strategies has focussed on influencing patient behaviour through incentives, reminders and alleviating patient burden, but has not sought to improve patient understanding of the importance of retention. Our aim is to assess how withdrawal, retention and the value of outcome data collection is described within the Patient Information Leaflets (PIL) used during consent. METHODS: Fifty adult or parent PIL from a cohort of trials starting between 2009-2012 and funded by the NIHR Health Technology Assessment programme were obtained from protocols, websites or by contacting trialists. A checklist of PIL content based on Health Research Authority (HRA) and ICH GCP Guidelines was supplemented with retention specific questions. Corresponding protocols were also evaluated to cross reference trial specific procedures with information communicated to patients. RESULTS: PIL frequently reiterated the patient's right to withdraw at any time (n = 49, 98%), without having to give a reason and without penalty (n = 45, 90%). However, few informed patients they may be asked to give a withdrawal reason where willing (n = 6, 12%). Statements about the value of retention were infrequent (n = 8, 16%). Consent documents failed to include key content that might mitigate withdrawals, such as the need for treatment equipoise (n = 3, 6%). Nearly half the trials in the cohort (n = 23, 46%) wanted to continue to collect outcome data if patients withdraw. However, in 70% of PIL using prospective consent, withdrawal was described in generic terms leaving patients unaware of the difference between stopping treatment and all trial involvement. Nineteen (38%) trials offered withdrawing patients the option to delete existing data. CONCLUSIONS: Withdrawal and retention is poorly described within PIL and addressing this might positively impact levels of patient attrition, reducing missing data. Consent information is unbalanced, focussing on patient's rights to withdraw without accompanying information that promotes robust consent and sustained participation. With many citing altruistic reasons for participation it is essential that PIL include more information on retention and clarify withdrawal terminology so patients are aware of how they can make a valuable contribution to clinical studies. There is a need to determine how retention can be described to patients to avoid concerns of coercion. Future research is needed to explore whether the absence of information about retention at the time of consent is impacting attrition.

Identifying research priorities for effective retention strategies in clinical trials.

BACKGROUND: The failure to retain patients or collect primary-outcome data is a common challenge for trials and reduces the statistical power and potentially introduces bias into the analysis. Identifying strategies to minimise missing data was the second highest methodological research priority in a Delphi survey of the Directors of UK Clinical Trial Units (CTUs) and is important to minimise waste in research. Our aim was to assess the current retention practices within the UK and priorities for future research to evaluate the effectiveness of strategies to reduce attrition. METHODS: Seventy-five chief investigators of NIHR Health Technology Assessment (HTA)-funded trials starting between 2009 and 2012 were surveyed to elicit their awareness about causes of missing data within their trial and recommended practices for improving retention. Forty-seven CTUs registered within the UKCRC network were surveyed separately to identify approaches and strategies being used to mitigate missing data across trials. Responses from the current practice surveys were used to inform a subsequent two-round Delphi survey with registered CTUs. A consensus list of retention research strategies was produced and ranked by priority. RESULTS: Fifty out of seventy-five (67%) chief investigators and 33/47 (70%) registered CTUs completed the current practice surveys. Seventy-eight percent of trialists were aware of retention challenges and implemented strategies at trial design. Patient-initiated withdrawal was the most common cause of missing data. Registered CTUs routinely used newsletters, timeline of participant visits, and telephone reminders to mitigate missing data. Whilst 36 out of 59 strategies presented had been formally or informally evaluated, some frequently used strategies, such as site initiation training, have had no research to inform practice. Thirty-five registered CTUs (74%) participated in the Delphi survey. Research into the effectiveness of site initiation training, frequency of patient contact during a trial, the use of routinely collected data, the frequency and timing of reminders, triggered site training and the time needed to complete questionnaires was deemed critical. Research into the effectiveness of Christmas cards for site staff was not of critical importance. CONCLUSION: The surveys of current practices demonstrates that a variety of strategies are being used to mitigate missing data but with little evidence to support their use. Six retention strategies were deemed critically important within the Delphi survey and should be a primary focus of future retention research.