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

Date Published: October 31, 2018

Publisher: Public Library of Science

Author(s): Anna Kearney, Anna Rosala- Hallas, Naomi Bacon, Anne Daykin, Alison R. G. Shaw, Athene J. Lane, Jane M. Blazeby, Mike Clarke, Paula R. Williamson, Carrol Gamble, Ali Montazeri.


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.

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.

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.

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.

Partial Text

The recruitment and retention of patients are acknowledged as major challenges in the delivery of clinical trials and represent key methodological research priorities [1, 2].

One hundred and fifty-nine HTA funded studies were identified through their website, of which 75 were eligible for inclusion. Fifty (66.7%) PIL and their corresponding protocols were obtained for analysis (Fig 1).

This study has collated PIL and examined in depth the information provided about retention. It was found that the majority of PIL reiterated the patient’s right to withdraw at any time without penalty and without giving a reason. However, many trials failed to include key information that might reduce unnecessary patient attrition or help assess its impact on the trial. For example, ICH GCP 4.3.4 states that whilst patients are not obliged to give a reason for premature withdrawal, reasonable efforts should be made to ascertain the reason [17] in order to assess potential bias and provide valuable feedback for future trials. 19 (38%) of trials sought to collect withdrawal reasons but only 6 (12%) communicated this to patients demonstrating the need for greater transparency to improve patient awareness and explain why disclosure can be beneficial.

With many people citing altruistic reasons for participation, improving understanding of treatment equipoise, importance of outcome data collection and continued follow up regardless of treatment adherence, may be an effective strategy to improve retention.




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