Rosamund Round

	It is well known with the pharmaceutical industry that a significant proportion of clinical trials fail due to challenges with patient recruitment and retention. And, with the shift towards patient centricity, incorporating the patient perspective into clinical trial design provides an opportunity to test and refine various elements to help achieve a balance between scientific rigor and feasibility of the study for participants. To do so, companies can utilize the following five tools to set themselves up for a successful trial:

	To create a patient-centric trial, it is crucial that researchers understand patients’ everyday lives and factors that could affect their participation, aside from simply the protocol’s eligibility criteria.

	A detailed profile of a trial’s patient population-and understanding who they are as individuals-can lead to creation of a more focused protocol that can set the trial on the path to success. Key issues to address in patient profiles can include:

		Demographics of the target patient population and exploration of how that may impact their lives. Are they elderly and may have difficulty leaving home? Are they young adults who can travel easily? Or, are they small children who must be supervised by parents?

		Type of treatment being tested may impact motivation. Is it curative or palliative?

		Payment. Will the costs of participating in the trial be reimbursed?

		Disease impact. What is life like for these patients day-to-day? Do patients have routine, frequent doctor appointments and/or hospitalizations, similar to trial site visits or interventions? Or do they have very few medical interventions, making trial-related testing and procedures more out of the ordinary?

	An accurate patient profile gives researchers a better idea of which real-world elements may have an impact on patients, participation, and how to plan accordingly. For example, would your participants prefer to have a lower visit burden or fewer invasive procedures? This can help researchers design their trials to make participation as easy and accessible as possible. Adjusting the conversation from “does this patient fit the eligibility criteria?” to “how would the practicalities of study participation impact their decision to join and remain in a trial? And how can we minimize the geographical, financial, and practical barriers to participation?” is key in patient-centric trial design.

	To get a better understanding of how a study may be received, directly surveying patients, caregivers, and nurses/physicians is recommended, as they are the ones with a practical view on the impact of the study design on the participant’s ability to join and remain on a trial. Eliciting such feedback seems like common sense, but is a relatively new approach in this context-and one that has shown great value.

	For example, in a study involving young children with severe epilepsy, there was initial concern that the three 72-hour hospital visits required by the protocol might be too intensive for the very young patients.  

	So, researchers surveyed caregivers to find out, on average, how many times in a normal year their children were admitted to the hospital and for how long. The results were surprising. Parents said their children were hospitalized about three to five times per year on a routine basis-and that most visits lasted at least three days. Therefore, the company concluded that the trial protocol did not place an undue burden on these already very sick patients and their families as the visit burden was similar to their standard of care. Since the required hospital visits were necessary to conduct a critical test, the company left the protocol intact. The survey did, however, uncover a different problem: parents reported that caring for their other, healthy children was the biggest challenge of epilepsy-related hospitalizations. With this feedback in mind, the company explored plans to work with sites to offer flexible visiting hours to simplify parents’ childcare responsibilities.  

	In recent years, patients have been more open with sharing their disease and treatment experiences online. “Listening” to online chatter in open forum can therefore offer unfiltered insight into what really matters to patients. Patient stories capture what it is like to live with a disease and may inspire new approaches and ideas.

	For example, one company developing a treatment for Crohn’s Disease read a number of blogs written by the children of Crohn’s sufferers and got a deeper perspective on how frightening the disease can appear to their families. They found information from family members about how Crohn’s patients can become alarmingly thin and weak, and that their children may worry that their parent will not survive. If their parent is hospitalized, some stay with relatives for extended periods, which can cause fear and upset. The number of stories online from the children and caregivers of Crohn’s patients indicated that the whole family is highly involved in and affected by treatment decisions. Therefore, to help optimize recruitment, the company tailored its educational materials to better ensure a joint decision-making process around trial participation.

	Another example is from a recent Alzheimer’s Disease (AD) study, where an analysis of web postings revealed that far more online chatter about AD came from caregivers than from patients. Therefore, an important component of the recruitment and retention strategy was to engage and educate caregivers by explaining the objectives of the study to them and treating them as partners. The web analysis also revealed that AD patient advocacy groups (PAGs) are very active online and are a trusted source of information and support. The company thus knew it would need to leverage existing relationships with PAGs, as well as forge new ones, in addition to high online visibility, to meet recruitment goals.

#4. Work with the Experts to Mitigate Study Burden

	As most patients have never participated in a clinical trial, there is often a lack of understanding about exactly what trial participation entails. So, while they are the experts on their own disease, direct feedback should be sought from elsewhere to successfully fill this gap in planning.

	Nurse specialists with deep experience at high performing investigative sites are among the most astute judges of the burdens a clinical trial can impose on patients. So, their analysis of the potential benefits and challenges of study participation is a valuable resource. Questions they can answer include:

		How does the burden of this study compare to the standard of care?

		What could be changed to make it easier for patients?

		What information will be most useful to support patients in learning about and participating in this study?

	Recently, a team of nurse specialists drawn from a network of top research sites helped make a protocol more patient-friendly by eliminating several planned patient questionnaires. Looking at the number, length and scope of these questionnaires, the nurses predicted patients would not respond well to answering so many questions so often during the study. Accordingly, researchers cut down some of the trial’s exploratory endpoints, reducing the number and length of the questionnaires.

	However, even experienced clinical staff can misinterpret patient perception on certain issues. For example, in a recent osteoarthritis study, experienced nurses were surveyed about the trial’s design and reported that home nursing visits in a protocol (versus visits at the investigative site only) would have no impact on a patient’s willingness to participate in a study. In contrast, a patient survey asking the same question showed patients viewed home visits as a positive benefit. The survey didn’t capture enough data to explain the reasons for this discrepancy, but it is possible the nurses’ responses were based on how attractive home visits were from their perspective as caregivers, rather than from the perspective of a patient. Therefore, careful analysis of data from all sources is required to ensure effective protocol optimization.

#5. Simplify and standardize informed consent

	Informed consent forms are notoriously long and confusing to participants. Simplifying the informed consent process will improve recruitment and retention numbers. One way to communicate complex information simply is to break the elements of a research study into a concise and accessible format.

	For example, a recent trial enrolling 5-to-11-year olds in the United States and South Africa had a complex schedule of events, including two mandatory overnight stays in the hospital. Patients and their parents needed a clear explanation of the trial’s procedures and expectations to provide informed consent. So, an animated video was developed (translated into the local languages) to explain the study’s activities and show how the drug worked. By providing the information in this way, parents and children gained a good understanding of what study participation would mean for them. Enrollment for this trial completed five months ahead of schedule and with no dropouts.

	Designing trial protocols with patients as the central focus does not require much additional work, yet can have a huge impact on its success. Planning ahead, taking the time to truly understand patients, and optimizing trial design with the practicalities for participants in mind can yield big rewards. By doing so, we can elevate recruitment and retention levels and maximize trial awareness, participation and retention, making it worth the investment. 

, Patient Centricity and Innovation Lead, PAREXEL International

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Companies can utilize the following five tools to set themselves up for a successful trial.

Rosamund Round

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