Example

 

“Study site personnel will review dosing information with the patient (or legally authorized representative) on scheduled clinic visit days, providing instructions regarding dose, dose frequency and the number of tablets to be taken for each dose. Patients (or legally authorized representative) will be instructed to keep all unused containers (empty, partially used, and/or unopened) for accountability at the next scheduled clinic visits. A compliance check and tablet count will be performed by study personnel during clinic visits. Study site personnel will record compliance information in the eCRF [electronic Case Report Form].

 

Every effort should be made to ensure patients return to the clinic with their study drug containers/unused study drug at each study drug dispensation visit. Study site personnel should conduct a verbal review of dosing with the patient and document the discussion in the patient’s medical record. This may serve as source documentation for the purpose of entering dosing data in the appropriate eCRF" [237]. 

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“All group sessions will be video-recorded and audited to ensure adherence to the program by two members of the research team. We will use standard methods for evaluating intervention fidelity, including observation of entire sessions for a randomly selected sample of 25% of sessions. Members of the research team will evaluate adherence to each session's goals and content. Consistent with best-practice recommendations for assessing treatment fidelity, [reference] this will be done using a checklist based on a standardized format adapted for the specific components of the SPIN-CHAT Program. The checklist will include the main session components (engagement via therapeutic recreation activities; education on information management and anxiety management through psychological and other strategies; open discussion and social support), and, for the educational component, will include the specific topics to be covered in each session" [228]. 

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Explanation

 

Fidelity to the intervention/comparator protocol is defined as the extent to which the intervention/comparator is implemented as planned in the protocol by care providers [238]. Adherence to intervention/comparator protocols refers to the degree to which the behaviour of trial participants corresponds to the intervention/comparator assigned to them (e.g., taking a drug, behavioural change, doing exercises [239]. 

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It is important to consider the research question (e.g., explanatory or pragmatic) when standardising the intervention/comparator and assessing fidelity and adherence [240-242]. In explanatory randomised trials, where the aim is to determine the treatment effect under ideal circumstances, the intervention is usually highly standardised with close monitoring of fidelity and adherence and use of strategies to increase them. Although there is no consensus on the acceptable minimum fidelity and adherence level in explanatory randomised trials, low fidelity and adherence can have a substantial impact on statistical power and interpretation of results.

 

To overcome the effects of non-fidelity and non-adherence, many trials implement procedures and strategies for monitoring and improving adherence, and any such plans should be described in the protocol. Monitoring could rely for example on biologic markers, direct patient observation, patient interviews, patient diaries, adherence questionnaires, pill counts, electronic monitoring of package entry, or ingestible smart sensors [243]. 

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Although each of the many types of monitoring methods has its limitations, [244] they can inform the interpretation of the trial result. It may be desirable to select strategies that can be easily implemented in clinical practice, so that the level of adherence in routine clinical settings is comparable to that observed in the trial.

 

In pragmatic randomised trials, which aim to determine the treatment effect in typical clinical settings, interventions are usually highly flexible with less focus on measuring fidelity and adherence, and less use of strategies to maintain or improve them. Nevertheless, assessing fidelity and adherence to the intervention/comparator or at least recording the most important components is necessary to understand what was actually administered to participants. This is particularly important for complex interventions where diversity in the implementation of the intervention/comparator is expected. For example, in a pragmatic trial assessing a surgical procedure where the procedure is left to surgeons’ choice, investigators should plan to systematically record key elements related to pre-operative care, anaesthesia, the surgical approach, and post-operative care. This information is essential to provide a relevant description of the intervention that was actually provided when the trial is completed.

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Reviews of two samples of 108 and 292 trial protocols from 2016 found that strategies to improve adherence were addressed in 86% to 90% of protocol [9, 10]. Authors should describe whether, when, and how fidelity and adherence to the intervention/comparator protocol were assessed [245]. They should pre-specify what is considered an adequate level of intervention/comparator delivery as planned. Any procedure to enhance fidelity or adherence to the intervention/comparator should be described. For pragmatic trials of complex interventions/comparators, authors should indicate which components and aspects of the intervention/comparator will be recorded and how.

 

Summary of key elements to address

• Strategies for improving fidelity of care providers and adherence of participants to intervention/comparator protocols, if applicable

• When and how fidelity of care providers and adherence of participants to intervention/comparator protocols will be assessed, if applicable

• Where appropriate, prespecified definition for classifying participants as being treated as planned or not.