In this blog for all those involved in Clinical trials are research studies involving people who use healthcare services. They often compare a new or different treatment with the best treatment currently available. This is to test whether the new or different treatment is safe, effective and any better than what is currently used. No matter how promising a new treatment may appear during tests in a laboratory, it must go through clinical trials before its benefits and risks can really be known., Katie Gillies and Derek Stewart, from the Trials Methodology Research Partnership and the Health Research Board Trials Methodology Research Network, highlight the need for focussed research on trial retention to help fill the evidence gaps identified in a national research agenda on retention to clinical trials developed and prioritised by all relevant stakeholders.
This blog was substantially revised by the authors on 10 May 2021
What do we know about the best ways to keep people involved in clinical trials? Frankly, not a lot.
Clinical trials can provide evidence about which treatments work. Clinical trials are research studies that involve people and compare different groups of people receiving different treatments and look at which treatments improve Outcomes are measures of health (for example quality of life, pain, blood sugar levels) that can be used to assess the effectiveness and safety of a treatment or other intervention (for example a drug, surgery, or exercise). In research, the outcomes considered most important are ‘primary outcomes’ and those considered less important are ‘secondary outcomes’. (like pain) the most. During the design of a trial, calculations are made about how many people need to join the trial and complete all of the Data is the information collected through research. collection requirements (which might be, for example, a questionnaire or a clinic appointment). These calculations allow the researchers to be confident in the results at the end of the trial.
If there are problems with keeping people involved in a clinical trial this can often result in a delay in completing the trial or problems in using the results to make informed decisions about clinical care. Identifying ways to keep people involved in trials, i.e. they provide all of the data or measurements that the trial needs, has been identified as one of the top priorities for research into the design and delivery of clinical trials.
What is already known about retention to clinical trials?
So, we don’t know a lot about how to keep people in trials but we do know a little. What we do know focuses on how to get trial participants to return postal questionnaires. Evidence from a recent Cochrane Reviews are systematic reviews. In systematic reviews we search for and summarize studies that answer a specific research question (e.g. is paracetamol effective and safe for treating back pain?). The studies are identified, assessed, and summarized by using a systematic and predefined approach. They inform recommendations for healthcare and research. Strategies to improve retention in randomised trials (March 2021) suggests that some approaches may improve return rates of postal questionnaires. However, we we are not able to say with confidence that any of the results we found is a true effect and not caused by other factors, such as flaws with the design of the studies. As such, the effect of ways to encourage people to stay involved in trials is still not clear and more research is needed to see if these retention methods really do work. Of the 70 relevant articles we identified only two of those investigated how best to encourage people to attend clinical visits as part of the trial follow up. Of the studies included in the Cochrane Review on strategies to improve retention to RCTs only a handful included patients as partners in their design – this needs to change. We should be involving trial participants in decision-making about how best to improve retention.
Where should research teams focus efforts?
The Cochrane review did, however, identify key strategies that research teams should focus on. The first set of priorities requires replication of evaluations of existing interventions using high quality evaluations of to provide evidence as to whether such strategies are effective or not. These four strategies all focus on are:
1. Monetary incentives: specifically, does giving a £5 gift voucher at same time as sending the questionnaire improve response to postal questionnaires.
2. Return postage: several return postage strategies have been evaluated to improve response of postal questionnaire e.g. reply paid compared to second class stamps, business post etc. Ensuring participants are not out of pocket is key, but which strategy to evaluate could be decided by the patient partners involved in the trial.
3. Pens: A number of studies have evaluated the inclusion of a pen with a postal questionnaire to improve response. It looks promising but further studies, specifically in trials that include younger populations with participants who are men are required.
4. Electronic reminders: emails or text messages reminding people (so sent in advance of the questionnaire) may also have an effect on postal questionnaire return. High quality replications are required.
These evaluations will help to provide evidence for trial teams as to what works to improve responses to postal questionnaires. They will begin to answer some of the questions identified as the top priorities for trials methodology retention research from a priority setting partnership (PSP) designed and delivered in A relationship between two characteristics, such that as one changes, the other changes in a predictable way. For example, statistics demonstrate that there is an association between smoking and lung cancer. In a positive association, one quantity increases as the other one increases (as with smoking and lung cancer). In a negative association, an increase in one quantity corresponds to a decrease in the other. Association does not necessarily mean that one thing causes the other. with the James Lind Alliance (JLA), the PRioRiTY II project. These prioritisation exercises help researchers and funders to focus on what matters most to all of those involved and ultimately contributes to global efforts to minimise waste in research by focussing activities. Future efforts to improve retention in trials should aim to target at least one of these stakeholder agreed priorities.
The past year has shone a bright light on the importance of clinical trials to provide evidence to inform health care decision making, But trials are only valuable if they recruit and retain enough people so that meaningful conclusions can be drawn from the results. Focussing efforts on keeping people in trials is effort well spent and will result in more valid and reliable result son which to base decisions for all.
Katie Gillies and Derek Stewart having nothing to disclose.