The rigor and complexity needed to generate measurable results from clinical trials often makes them difficult for patients to participate in. And that’s a problem for the biopharma industry.
The more complex a trial is and the more procedures performed per patient visit are both associated with higher failure rates for recruitment, randomization, and retention.
Despite knowing that-less burdensome protocols would help optimize trial designs, accelerate recruitment, and reduce attrition, sponsors have struggled to bring the patient perspective into the trial design conversation. Their lack of success is due in part to how differently the two groups communicate.
Scientists like their insights captured via validated instruments that organize data into quantifiable outputs that can be measured and managed. Patients want to tell stories, share anecdotes, and talk about the qualitative factors that affect their quality of life. These disparate communication preferences have made it difficult for the two groups to engage, or for scientists to translate those qualitative stories into systematic assessments that quantify the burden placed on study volunteers.
That may be changing.
Over the past two years, we have been part of a team of researchers from Tufts University’s Center for the Study of Drug Development and from IQVIA that has been developing a new metric called the patient friction coefficient, which we described recently in the journal Clinical Therapeutics. This data-informed measure characterizes and quantifies the potential burden of participating in a clinical trial. The tool offers a logical and validated method to capture information about burden at every stage of the clinical trial experience for each potential participant, from the point at which they first learn about a research opportunity, through recruiting, participation, and follow-up once the trial is complete.
This metric can give trial developers the information they need to quantify which patient burdens will have the biggest impact on their recruiting and retention goals and make changes to ease those burdens without affecting trial results.
How the patient friction coefficient works
Developers generally assume that taking part in a clinical trial adds some incremental burden for participants. The patient friction coefficient framework makes it possible to quantify that impact by testing how much of the perceived burden of participation exceeds the burden an individual already experiences from treatment. It can also quantify individual’s perceptions of the benefits of participation that that offset burdens, such as the option to receive infusions at home that aren’t routinely part of existing treatment, being provided with transportation to and from study visits, or more frequent interactions with specialists.
The patient friction coefficient assessment considers various elements that can affect an individual’s willingness to participate in a clinical trial, including time and travel burdens, invasive procedures, and concerns about replacing their current treatment and trusted physician with an unknown treatment and care team.
Patients and caregivers are surveyed using the patient friction coefficient assessment tool about how the protocol of a trial would affect their willingness to participate in it. The protocol is then assigned a patient friction score. At the same time, real-world data are used to characterize the type and frequency of procedures performed in the clinical setting for the target patient population.
This relatively simple patient-centric formula offers researchers and trial participants several advantages: It uses available data. The grouping of variables maintains transparency and makes it straightforward to replicate and validate. And the coefficient can be calculated for an individual or a group of similar individuals, which allows planning decisions around inclusion and exclusion criteria for protocol development, among other things.
Putting the patient friction coefficient to use
The insights generated by the patient friction coefficient make it possible for trial sponsors to rapidly determine which protocol design decisions positively or negatively affect recruiting and retention, how significant the impact will be, and how those risks vary across patient populations. For example, travel times may be only a minor burden to participants who live within a 25-mile radius of the trial center or for those who own a car. But it may be substantial enough to prevent participation for those who live farther away or rely on public transportation. Similarly, working professionals may perceive weekly site visits as overly burdensome, whereas older patients may be accustomed to this cadence of health care engagements.
The patient friction coefficient introduces the patient experience into the trial design process in a scientifically valid way. It gives researchers a way to evaluate their protocol design choices through the lens of patient burden and to score their options for straightforward and robust comparisons. By introducing a measure of burden into the trial design process, they can create more patient-centric experiences that will ultimately help accelerate recruiting and improve retention.
The tool can also play an important role in engaging with potential trial participants. Adopting this tool opens lines of communication between participants and trial designers and can establish clearer expectations about requirements for trial participation and how they differ from normal clinical care.
All of these benefits can help lower recruiting costs, reduce the risk of attrition, and support a faster path to market.
At first, users will likely employ the coefficient retrospectively to identify factors that contributed to low enrollment and retention in past trials, as a way to learn lessons from mistakes and inform future protocol design policies.
Over time, it will be used during protocol planning and design to reduce or offset — and ultimately avoid — inefficient practices and better predict clinical trial performance.
We believe this framework will help change the fundamental culture around trial design by making the patient perspective an inherent part of every protocol conversation. Since patient friction coefficient values are comparable across trials, ascribing one to a trial will call out patient burden as an essential design variable.
For several years, the pharmaceutical industry has tried to become more “patient focused.” Many clinical trial sponsors have made bold declarations about treating patients as stakeholders and incorporating their feedback into protocol designs to reduce the burden of participating in clinical trials. The patient friction coefficient offers a straightforward way to do this while also making it as prominent a part of the protocol selection process as feasibility, cost, timing, and safety.
Since the patient friction coefficient framework is a new metric, its developers look forward to working with innovative companies to test it against their past and future trials. We will continue to refine the features and weighting mechanisms through these early pilot projects to ensure its reliability and ease of use.
We see the patient friction coefficient as a strong example of the power of human data science and proof that combining patient-level data with advanced analytics tools can yield valuable insights to improve trial design. It is one way to solve the constant challenge of meeting recruitment and retention goals.
David Cameron is the senior director and global head of novel trial design at IQVIA. Murray Aitken is the executive director of the IQVIA Institute for Human Data Science.