Item 11c: Strategies to improve adherence to intervention protocols, and any procedures for monitoring adherence (e.g., drug tablet return; laboratory tests).
“Adherence Reminder Sessions
Face-to-face adherence reminder sessions will take place at the initial product dispensing and each study visit thereafter. This session will include:
- The importance of following study guidelines for adherence to once daily study product
- Instructions about taking study pills including dose timing, storage, and importance of taking pills whole, and what to do in the event of a missed dose.
- Instructions about the purpose, use, and care of the MEMS® cap [medication event monitoring system] and bottle
- Notification that there will be a pill count at every study visit
- Reinforcement that study pills may be TDF [tenofovir disproxil fumarate] or placebo
- Importance of calling the clinic if experiencing problems possibly related to study product such as symptoms, lost pills or MEMS® cap.
Subsequent sessions will occur at the follow-up visits. Participants will be asked about any problems they are having taking their study pills or using the MEMS® cap. There will be brief discussion of reasons for missed doses and simple strategies for enhancing adherence, e.g., linking pill taking to meals or other daily activities. Participants will have an opportunity to ask questions and key messages from the initial session will be reviewed as needed . . .
To enhance validity of data, multiple methods will be used to assess medication adherence including pill count; an electronic medication event monitoring system (MEMS® cap) [Reference X]; and ACASI [audio-computer administered interview] questionnaire items including a one month visual analogue scale [Reference X], reasons for non-compliance, and use of the MEMS® cap. Participants will return the unused tablets and bottle at each follow-up visit. Unused tablets will be counted and recorded on the appropriate CRF [case report form]. Electronic data collected in the MEMS® cap will be downloaded into a designated, secure study computer.” 153
Adherence to intervention protocols refers to the degree to which the behaviour of trial participants corresponds to the intervention assigned to them.154 Distinct but related concepts include trial retention (Item 18b) and adherence to the follow-up protocol of procedures and assessments (Item 13).
On average, adherence to intervention protocols is higher in clinical trials than in non-research settings.155 Although there is no consensus on the acceptable minimum adherence level in clinical trials, low adherence can have a substantial impact on statistical power and interpretation of trial results.156-158 Since fewer participants are receiving the full intervention as intended, non-adherence can reduce the contrast between study groups – leading to decreased study power and increased costs associated with recruiting larger sample sizes for evaluating superiority, or leading to potentially inappropriate conclusions of non-inferiority or equivalence. There is also the possibility of underestimating any efficacy and harms of the study intervention.
Furthermore, if adherence is a marker for general healthy behaviour associated with better prognosis, then different rates of non-adherence between study groups can lead to a biased estimate of an intervention’s effect. In support of this ‘healthy adherer’ effect, non-adherers to placebo in clinical studies have been found to have poorer clinical outcomes than adherers.159
To help avoid these potential detrimental effects of non-adherence, many trials implement procedures and strategies for monitoring and improving adherence,67;156-158 and any such plans should be described in the protocol.160 Among applicable drug trials published in 1997-99, 47% reported monitoring the level of adherence.161 Although each of the many types of monitoring methods has its limitations,157;158 adherence data can help to inform the statistical analysis (Item 20c), trial interpretation, and choice of appropriate adherence strategies to implement in the trial as it progresses or in future trials and clinical practice.
A variety of adherence strategies exist,156-158 and their use can be tailored to the specific type of trial design, intervention, and participant population. It may be desirable to select strategies that can be easily implemented in clinical practice, so that the level of adherence in the real-world setting is comparable to that observed in the trial.158
|11b: Interventions – Modifications||11d: Concomitant care|