Consideration of adherence to pharmacological interventions in publishing guidelines and protocols for clinical trials in covid-19

Background

In any clinical trial involving a pharmacological intervention, adherence to the intervention can be a problem. It is difficult for those taking part in a clinical trial of a medicine to remember to take it in the right dose at the right times, and to continue to take it regularly throughout the period of the trial.

      However, poor adherence in a trial has several important consequences [1]:

• an effective medicine may not be found to be effective because it wasn’t taken properly;
• in that case the dose of the medicine may be increased unnecessarily in later trials, with resulting toxicity;
• useful medicines may not become available;
• important harms may be missed;
• in the case of drugs used for infections, resistant organisms may emerge;
• the costs of drug development can increase.

It is therefore important that those conducting clinical trials should take steps to try to improve adherence as much as possible and to measure it. Furthermore, when the results of trials are reported, the published reports should include information about how adherence to the intervention was encouraged, how it was measured, and how good it was.

Publishing guidelines and protocols for clinical trials

One way of encouraging good practice in clinical trials is to require authors of published reports to give specific pieces of information. This is done by asking them to follow specific guidelines for reporting. The first such guideline, CONSORT (Consolidated Standards of Reporting Trials), was introduced in 1996 [2], and since then many other guidelines have been introduced. However, adherence is rarely if ever mentioned in the guidelines, and it is often not mentioned in published protocols for clinical trials.

Project aims:

This project will be in two parts:

1. A survey of the currently available guidelines (467 in all) published on the EQUATOR website [3] to document the extent to which adherence is discussed in each. A word search on the EQUATOR website for the word “adherence” yielded only three hits, one of which is the ESPACOMP Medication Adherence Reporting Guideline (EMERGE). Not all of the guidelines will be eligible for inclusion in this survey. Part of the research will be to classify the guidelines into those that ought to mention adherence and those that need not.

The next step will be to make recommendations about how adherence should be included in guidelines. It may be necessary to develop different recommendations for the different types of guidelines that are eligible for inclusion.

2. A parallel study will be undertaken, to determine the extent to which adherence is mentioned in protocols for clinical trials (RCTs) of pharmacological interventions in covid-19. These protocols are listed on the WHO’s website and are available in full through the websites on which they are posted (e.g. clinicaltrials.gov).

References

1. Breckenridge A, Aronson JK, Blaschke TF, Hartman D, Peck CC, Vrijens B. Poor medication adherence in clinical trials: consequences and solutions. Nat Rev Drug Discov 2017; 16(3): 149-50.
2. Begg C, Cho M, Eastwood S, Horton R, Moher D, Olkin I, Pitkin R, Rennie D, Schulz KF, Simel D, Stroup DF. Improving the quality of reporting of randomized controlled trials. The CONSORT statement. JAMA 1996; 276(8): 637-9
3. The EQUATOR Network. Enhancing the QUAlity and Transparency Of health Research. https://www.equator-network.org/reporting-guidelines/.