Putting Patients First

Setting up a clinical trial resembles an assembly line that has adapted little with time and fails to reflect the importance of patients. This assembly line of sorts (Figure 1) includes three distinct phases: design, planning, and implementation. Design begins with the protocol. Planning includes interviewing key opinion leaders, conducting site feasibility, and selecting and training study sites. At implementation, clinical teams hand over responsibility for study success to sites, with the hope that sites will actually deliver the subjects they identified during the feasibility study; unfortunately, that all too often fails to occur.

Figure 1. This typical "assembly line" approach toward clinical trial set-up can lead to rescue mode.

It is time to take a hard look at the flaws that send studies into rescue and can undermine enrollment. The main cause of recruitment failure? The process does not involve patients.

A Strategic Shift

A fundamental shift toward thinking both tactically and strategically can break the cycle. Increased recruitment success requires recognizing that patients can offer as much to planning as sites and opinion leaders. Strategic thinking focuses on achieving overall goals, such as recruiting the right patients and retaining subjects until study conclusion. Tactical thinking looks at short-term objectives that will move the study closer to its goals. Driven by an urgent first-patient-in objective, clinical teams often launch a recruitment program without any input from patients.

Benefits of Involving Patients Up-front in the Recruitment Process

Ironically, one could argue that the pharmaceutical industry had a more progressive approach to involving patients in clinical trials several decades ago than they do today. Strategies developed in therapeutic areas with extensive patient activism: cancer and AIDS. At the behest of activists, companies involved patients in an exchange of ideas about clinical protocols. Burroughs Wellcome (now Glaxo-SmithKline) and Rhone Poulenc Rorer (now sanofi-aventis) promoted such discourse with patients, somewhat timidly at first; but they soon recognized the insight gained from listening to patients.

To place that era in context, patient activists in the 1980s demanded to know about their treatment and available clinical trials. Patients established the right to some autonomy about health care decisions. Granted, they wanted an expanded range of drugs; but, with more widely advertised clinical studies, patients increased their demand for feedback and the right to know. The movement reached equilibrium: Patients learned from clinical teams, which learned from patients.

Tackling Uncertainty

Clinical teams often believe that a tactical step-by-step planning involving principal investigators and sites removes study uncertainty. In reality, uncertainty remains unless the team involves patients at each step.

Complex clinical protocols involve more medical procedures and require more time; they increase the burden on subjects. A Tufts Center for the Study of Drug Development analysis of more than 10,000 clinical protocols highlights the burden.¹ Consistent with industry's focus, they analyzed sites' work loads, not subjects' burdens. Few companies apply the key learnings and best practices learned in the 1980s. Few systematically involve potential subjects in the protocol assessment. Consequently, few realize that doing so can improve recruitment success rates.

To address this shortcoming, we involve patients at different points in the planning phase and protocol design. We simulate the informed consent process, study visits, and study participation with real patients. This assessment incorporates both tactical and strategic approaches. It identifies critical barriers and issues that can undermine a study's recruitment and retention strategy. We listen to what patients say and incorporate their feedback into the clinical trial process. Although the process takes seven to 14 days, it delivers time and cost savings.

Figure 2. This model uses market research with patients and Patient Protocol Peer Reviews to reduce uncertainty in patient recruitment and improve forecasting. Market research also assesses factors such as approachability of the patient and willingness of patients to participate in a trial.

By overlooking patients, clinical teams can unknowingly create an environment that causes missed deadlines, enrollment problems, and a need for rescue. Recruitment uncertainty increases when little is known about how patients see the study's design and purpose, assess the benefit:risk equation, perceive the research process, and envision gaining from participation. This knowledge forms the basis of a patient-centered recruitment strategy.

Consider an oncology study in rescue because eligible patients were not being enrolled. The clinical team held talks with study sites about the recruitment problem, to no avail. Missing from those talks were first-hand responses directly from patients and families. Focus groups, surveys, patient panels, and one-to-one discussions were conducted midstream. Had those steps taken place at the outset, they would have identified crucial issues. The clinical team would have learned that cancer patients saw university- and government-sponsored trials as unbiased but perceived industry-sponsored trials as biased and that one-fifth of cancer patients feared losing control of decision-making, felt coerced to join a trial, and/or disliked the idea of being experimented on. Knowing about those issues in advance, the team could have provided educational material to those sites, and strategies to address patients' concerns.

Patient-Centric Planning

A recruitment strategy validated by market research reduces uncertainty. Campaigns based on guesswork or personal bias face a greater risk. At the core of successful recruitment is knowing what makes patients willing to volunteer as subjects and stay until the study ends. Despite the logic of including patient input in a recruitment strategy, patient-centric recruitment is rare.

These days, we hear a lot about recruitment numbers, tactical numbers that predict outcome, measure rates, assess return on recruitment investment, forecast time to enrollment completion. None of those numbers can be accurately assessed without market research and feasibility information. Accurate performance predictions must answer critical questions: What percentage of qualified patients will be approached? Once approached, how receptive will they be to taking part?

Involving patients in planning and implementation not only guides teams in the development of more realistic protocols, it also opens up new ways of selecting sites, designing recruitment and retention materials, and achieving recruitment and retention success. From design to planning to implementation, putting patients first provides the strategic clarity necessary to deliver results. It is the "softer" market research data that drives the metrics for predicting recruitment-retention success.

Liz Moench is president and CEO of the MediciGroup, dba MediciGlobal.

References

1. K. Getz, J. Wenger, R.A. Campo, E.S. Seguine, K.I. Kaitlin. "Assessing the Impact of Protocol Design Changes on Clinical Trial Performance," American Journal of Therapeutics 15 (5) 450-457.