3 Surefire Ways To Design Trials That Patients Want And Need

By Robert Den, MD, chief medical officer, Alpha Tau Medical

The development of new drugs and medical devices often progresses through a well-established research trajectory, beginning with studies on simple organisms like fruit flies and zebrafish. This research then advances to more complex mammals, including mice, rats, and primates, before reaching the final stages of clinical trials in humans. What is notably absent throughout this progression, however, are the voices of patients who suffer from the disease or condition being studied, as well as those of their families and caregivers. In most cases, researchers have not spoken directly with a patient experiencing the very disease that is the focus of their work.

This lack of patient involvement poses a significant challenge in the design and execution of clinical trials. While it intuitively seems that patient-centric trials would yield better outcomes, as they are designed to improve the quality of research and its relevance to patients^[1], there has historically been little objective evidence to support this belief, until recently. Over the past decade, a growing focus on patient-centered trial design has produced new evidence showing that trials incorporating patient input are not only more successful but also completed more quickly and are more cost-effective than those lacking a patient-centric approach.

For example, a study from the Economist Intelligence Unit (EIU)², the research and analysis arm of The Economist Group, a sister company of The Economist magazine, found that drugs developed using patient-centric designs were more likely to be launched than drugs developed without such a focus, with a percentage point difference of nearly 20% (87%) from the control group (68%). The same study found that patient-centric trials took less time to recruit 100 participants (four months), compared to the control group (seven months). While the reasons for the time reduction were unclear, the study concluded that the nature of a patient-centric approach implies “more effective mechanisms of engaging patients.” 

A second study³ conducted by the Tufts Center for the Study of Drug Development (CSDD) and the Clinical Trials Transformation Initiative (CTTI), a public-private partnership of the FDA and Duke University to develop and drive practices to increase the quality and efficiency of clinical trials, developed a method for projecting the financial value of patient engagement. The study found that a $100,000 investment in a patient-centric initiative during the design of a study for a typical oncology development program entering a Phase 2 or 3 clinical trial could yield an ENPV (expected net present value) of 500 times that amount — the equivalent of accelerating a pre-Phase 2 product launch by 30 months and a pre-Phase 3 project launch by 18 months.

Planning Trials With Patients, Not Just With Patients In Mind 

Considering the clear advantages of a patient-centric approach, one would expect patient-centricity to be a fundamental aspect of clinical trial design. Yet according to the EIU⁴, the rate at which patient-centric approaches are being adopted is still “surprisingly low.”⁵ In a survey of 25 leading research institutions, the global consulting company Huron found that about 60% of sponsors and CROs⁶ now strive to cultivate relationships with patients to gain insight into their perspectives, either in person or through online forums. Though this percentage has increased, according to the CTTI, a major factor in the considerable room for improvement reflected by this number is a lack of information on how to “operationalize” a patient-centric approach.⁷  

As a radiation oncologist, I have been involved in clinical trials across a broad variety of malignancies. In my current role as chief medical officer at Alpha Tau Medical⁸, whose innovative Alpha DaRT⁹ technology aims to significantly optimize the efficiency, safety, and convenience of cancer treatment, I am involved in seven ongoing trials at leading cancer centers around the world for cancers of the skin, oral cavity, prostate, pancreas, breast, liver, and lung. In addition to our ongoing trials, we are actively recruiting for trials for other cancer indications. In the design of our trials, we make patient centricity a priority, just as we have made putting patients first a part of our mission. 

Below are three ways to make trials more patient-centric:

1. Involve patient advocacy groups

One way to increase patient centricity is through patient advisory boards. But trial sponsors may not find it feasible¹⁰ to create boards that are representative of various types of illnesses and patient demographics, and smaller sponsors and CROs may not have the resources to create patient advisory boards at all. An alternative is to involve patient and/or disease advocacy groups, which can provide real-world insight into what treatments patients want, what trial requirements would work best for them, and what it’s like to live with a specific condition. A relationship with a highly regarded patient advocacy group¹¹ also can help clinical trial sponsors gain the trust of potential trial enrollees and offer “convening power”¹² with other stakeholders that they might otherwise lack. 

According to a set of recommendations for patient group involvement issued by the CTTI¹³, including the patient perspective early in the development cycle can result in a clearer understanding of the unmet need and the therapeutic burden, as well as a more targeted design and increased opportunity for expanding indications. It may also result in an improved selection of participants, endpoints, and clinical sites. Lastly, it may result in faster recruitment, increased patient compliance with the trial protocol, and a reduction in the need for costly and time-consuming adjustments later in the study.

2. Decentralize clinical trials

During the COVID pandemic, decentralized clinical trials (DCTs), in which the trial comes to the patient instead of vice versa, became commonplace. Because of the infection risk posed by travel in general and by hospitals in particular, trial participants were accommodated through innovative digital technologies such as telehealth calls, mobile apps, and wearable devices that eliminated the need to travel to often-distant clinical research centers. Instead, participants could participate from their homes or local healthcare facilities or laboratories.

Although the pandemic has passed, the recognized benefits of DCTs have now firmly established them in the mainstream. One benefit is shorter development cycles, which translate into major cost savings. Though 85% of trials experience costly delays, those employing wearable devices and mobile apps are less likely to be delayed, according to a Tufts study¹⁴. Because of their greater convenience, DCTs also improve patient recruitment and retention, another source of delay and expense. About 50% of trials are not completed due to insufficient enrollment, and 30% of participants who agree to participate will drop out.¹⁵ The same Tufts study found that wearable devices and mobile apps significantly decrease screen failure and dropout rates. In fact, the study concluded that the reductions in development cycle time associated with DCT deployments had a greater impact on net financial benefits than any other factor.

By reducing barriers to participation, DCTs also increase the number and diversity of trial participants, including age, race, gender, and ethnic diversity, thus increasing the quality and relevance of trial results.

3. Reduce patient burden

By reducing patient burden, DCTs play a major role in promoting trial participation. But patient burden also can be reduced in other ways. About 85%¹⁶ of patients say they are willing to participate in clinical trials, but fewer than 5% do. Barriers include transportation, childcare, work arrangements, and more. Increased input from patients on their needs and preferences often results in burden-relieving changes in trial design that are easy and inexpensive to implement. In collaboration with ZS Associates, a global management consulting firm, Tufts CSDD has developed and tested¹⁷ a clinical trial participant burden algorithm that includes factors such as mobility, protocols and procedures, logistics and convenience, medication adherence, lifestyle restrictions, and caregiver reliance. An example of one of the innovative tools being developed to increase patient-centricity, is the participation burden algorithm is highly associated with — and predictive of — clinical trial performance outcomes. Research is underway to prospectively apply it to protocol design.

The Importance Of Clarifying Goals And Objectives

While involving patients in trial design and protocol offers many benefits, sponsors need to keep in mind that the backgrounds, perceptions, and interests of sponsors and their patient collaborators may not always be aligned. Sponsors must balance patient input with scientific understanding, as well as with business, legal, and regulatory requirements. To avoid potentially costly conflicts and delays, it is important to clarify expectations and delineate the rules of engagement from the outset. A set of recommendations for patient group engagement¹⁸ developed by the CTTI suggests spelling out the scope of involvement and the nature of the commitment in a document such as a simple contract or a memorandum of understanding. Confidentiality or non-disclosure agreements may also be necessary to protect the sponsor’s interests. Potential risks associated with patient involvement can be mitigated through close communication with the FDA and the institutional review board. Lastly, it’s important to involve patients throughout the research and development continuum — “from bench to bedside and back,” as the CTTI puts it. Patients should be true partners in the development process, not just tokens.

The process of developing a drug or medical device in the United States is long, arduous, and costly. The Tufts CSDD puts the total capitalized cost for a new compound at $2.6 billion.¹⁹ While there is a moral and ethical case for involving patients in clinical trial design, recent research shows that there is a pragmatic one as well. Among the many strategies for reducing costs and speeding the development cycle, involving patients in clinical trial design in thoughtful ways that protect the interests of sponsors and their patient collaborators may yield one of the biggest payoffs.

References:

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About The Author:

Robert Den attended Yale University and received his medical degree from Harvard Medical School in 2006. He is chief medical officer at Alpha Tau Medical, where he leads clinical research functions. He is also an associate professor of radiation oncology, cancer biology, and urology at Thomas Jefferson University.