Boosting patient recruitment and retention in clinical trials – fresh approaches?

Wpatiente hear much about ‘patient centricity’ and ‘empowering patients’ in clinical trials and research as well as everyday clinical practice.  This can be defined loosely as the process of designing a service or solution (e.g. a clinical trial) around the patient.  For clinical trials, this can mean engaging in a dialogue with potential patients or their families about the design of the trial itself including the protocol, trial schedule, number of interventions etc. so that it is considered acceptable and to try and ensure visits and data recording are made as easy as possible.  All this is to be achieved without compromising the scientific integrity and validity of the trial.  So although a good measure of pragmatism is called for one must still not lose sight of the trial’s aims and the necessary information required to achieve them.

The importance of being able to recruit sufficient patients as well as keep them ‘on study’ for as long as possible (one hopes for the full planned duration….) cannot be over-stated. Thus sponsors and researchers are always looking for ways to achieve this.  We know that it is not uncommon for trials to falter because the expected source of willing patients somehow dries up or, once recruited, they do not manage to stay the course.  This prolongs the timescale and compromises data.

In one such instance of attention to successful recruitment and retention, researchers at Nationwide Children’s Hospital (Columbus, Ohio USA) found ways to increase the number of people recruited and retained in one of their trials quite significantly. This was by seeking the advice of patients, families and other stakeholders in the design of a clinical trial investigating paediatric appendicitis.

The changes were made after the study had been initiated at the recommendation of a group of 20 individuals who are stakeholders on the research team, including (as appropriate to the paediatric study) children 7 to 17 years old, their families, physicians, nurses, patient educators and payers. The stakeholders provided input and advice to the researchers about all phases of the ongoing clinical trial in which the use of a tablet / smartphone app called Patient Activation Tool (PAT) is being investigated [1]. Changes were introduced to the patient information script, which initially simply said that they were ‘investigating a tool designed to improve decision-making about appendicitis treatments’ to a longer two-part message mentioning: i) aim to improve ‘the way in which the medical team communicates with families’ and ii) explanation to families that the study is ‘testing a tool designed to improve both physician-patient communication and promote shared decision-making about treatments’.  Simple changes in wording, but these were to yield impressive results.

To improve retention, the recommendation was to offer an online option via an e-mailed link for participants to complete follow-up questionnaires, to attain preferred times of contact and send out reminder letters about the follow-up assessments.

After these rather more patient/family-centred changes in information and simplifying provision of required data to reduce clinic visits were adopted into the study, rate of enrolment increased from 65 percent to 95 percent and the retention rate increased from 58 percent to 85 percent.  These are indeed encouraging statistics, which are reported in a communication to JAMA surgery [2].

Reportedly, the clinicians involved in the study were themselves surprised at the magnitude of the effect of the changes since recruiting patients for clinical trials, particularly those involving non-elective surgery, is often challenging with recruitment rates for paediatric clinical trials usually being under 50 percent. The study authors made the point that some people just don’t want to be part of research whilst others are afraid of the prospect, perhaps feeling like they are going to be ‘guinea pigs’ [3] . So it is important to approach them in such a way that they understand why it is important and why the results would be important to them or to others just like them.

Retaining those patients who do agree to enrol in a clinical trial is often difficult because it can be time-consuming for patients and their families to fill out the often lengthy and highly detailed follow-up questionnaires. The families of patients treated for conditions such as appendicitis are typically cured or feel better after treatment, so there may be little incentive to take the time to fill out the questionnaires.

The resulting jump in recruitment and retention rates from the study in question underscores the value of involving patients, families and other healthcare professionals when designing and performing clinical trials and making data reporting as patient-friendly as possible.

As we have seen in a previous post on this site [4] there are potential statistical implications in trying to deal with missing data in follow-up analyses when patients ‘drop out’ or do not adhere to the protocol properly – the more patients that are lost for follow-up, the further an analysis deviates from true ‘intention to treat’.  Patient-friendly approaches to data collection therefore aid statistical integrity and accuracy.

It is clear that many research approval Authorities now acknowledge the importance of ‘patient centricity’ and due regard for the role of patients and their families as well as other tangentially involved personnel when considering participation in clinical trials.  Indeed, for clinical trial or research approval applications some reviewing bodies specifically consider whether or not researchers have involved input from patients and stakeholders other than the researchers and sponsors themselves in the trial process.  For instance in the UK’s HRA (Ethics & Management) online application system one question to be addressed is:  In which aspects of the research process have you actively involved, or will you involve, patients, service users, and/or their carers, or members of the public?  Applicants have to tick which of the areas of research to which this applies: Design / Management / Undertaking / Analysis of results, and give details or ‘justify the absence of involvement’.  Although there may be instances where ‘justification’ of no such involvement may not be appropriate, this is a clear message that the authorities are now taking the matter seriously and directing researchers to consider these approaches.

The results of taking advice from a ‘stakeholder’ panel reported by the researchers at Nationwide Children’s Hospital in Ohio show that these considerations can produce dividends.  If you are a sponsor or researcher looking to place responsibility of designing, setting up or managing a clinical study, my advice would be to check with the research organisations being considered to see what ‘patient-centric’ solutions they offer in order to make your study run smoothly and to schedule.

Brian Cary

[1] Randomized Controlled Trial of a Patient Activation Tool in Pediatric Appendicitis (Antibiotics Alone vs. Appendectomy) https://clinicaltrials.gov/ct2/results?term=02110485&Search=Search

[2]  Minneci PC, et al., Improving Surgical Research by Involving Stakeholders. JAMA Surg. 2016 Feb 10. (doi: 10.1001/jamasurg.2015.4898).

[3] http://www.news-medical.net/news/20160212/Researchers-find-new-way-to-increase-patientse28099-recruitment-retention-in-clinical-trials.aspx

[4] https://clinicalaccelerator.com/ Statistical Controversies in Reporting of Clinical Trials Posted on March 14, 2016

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