Clinical Researcher—October 2022 (Volume 36, Issue 5)

PRESCRIPTIONS FOR BUSINESS

Scott Gray

 

For some patients, participating in a clinical trial may be the only way to secure treatment when no other approved options are available. Others altruistically choose to participate in clinical trials to advance science and help future patients who may be suffering from the same disease. In either case, there is a real human need contingent upon clinical trials meeting their targeted enrollment, retaining participants, attaining crucial milestones, and resulting in successful outcomes. Yet, despite the best efforts of study stakeholders, recruitment and retention continue to be challenges for the industry and the most significant cause of trial delay.

Two-thirds of clinical trials fail to enroll enough patients to conduct the trial effectively,{1} and 85% of trials fail to retain enough patients to complete the study.{2} Even after patients are successfully enrolled, clinical trial coordinators face an uphill battle in retaining patients for the duration of the study; dropout rates typically exceed 30%.

Recruitment and retention problems have a cumulative effect, often resulting in trial delays. Only 6% of clinical trials finish on time, and 80% are delayed by at least one month.{3} Delays negatively impact study costs and future sales, causing the industry potential losses of between $600,000 and $8 million per day.{4} The toll of these delays on humans, however, is immeasurable.

Despite these challenges, pharmaceutical sponsors and clinical research organizations (CROs) are working to increase patient recruitment and retention rates and to improve trial performance using patient-centric engagement strategies to elevate the patient experience.

The Patient’s Role in Clinical Trial Return on Investment (ROI)

The cost of developing a new drug is enormous. An often-cited study by the Tufts Center for the Study of Drug Development{5} calculated an average of $2.6 billion, while a study in JAMA Internal Medicine{6} suggested an average of closer to $1.3 billion. Trial costs vary greatly, of course, driven by several factors, including the number of patients required to establish a treatment’s efficacy and the number of site visits needed for the treatment to be effective. At one time, the median cost of clinical trials for new drugs seeking approval from the U.S. Food and Drug Administration (FDA) was estimated to be $19 million.{7}

In comparison, trials with more than 1,000 patients had an average cost of $77 million,{7} and pivotal (Phase III) studies for new drugs approved by the FDA cost a median of $41,117 per patient.{8} According to one report submitted to the U.S. Department of Health and Human Services, the range of requisite investment for clinical trials and each patient enrolled in a trial is as broad as the number of studied diseases.{9}

However, what if we considered these figures from another angle: the pharmaceutical industry cannot exist without patients. Rather than looking at patients as a cost to clinical trials, why not consider the value of their participation?

For example, look closely at the commercialization of a well-known drug treating multiple sclerosis. The drug has been on the market for five years, is prescribed often, and the sponsor has realized substantial revenue and ROI from their clinical investment, with total earnings of approximately $17.5 billion at the time of this article. The clinical trials supporting the drug’s initial FDA approval involved 1,656 patients.{10}

In other words, each trial participant who enabled the drug to get to market resulted in more than $10.5 million in revenue.

Much of a drug’s success can be attributed to its clinical trial participants, without whom the drug would not achieve commercialization. The revenue estimate is a rough calculation, but the figure illustrates the value of patient participation and the potential return on investment for trial completion. Of course, the improved quality of life for the patients who gain access to a novel treatment is immense.

The stakes are considerably higher in trials for rare diseases{11} (defined in the United States as those affecting less than 200,000 people), with fewer eligible patients and a greater need to keep patients enrolled and engaged through trial completion. Patient scarcity exponentially increases the value of rare disease trial participation.

The rarer the disease, the more significant the potential is for smaller patient populations with clusters in disparate geographic regions. Thus, the travel burden associated with these trials typically increases, as trial sites are generally restricted to specific, well-known institutions in large urban centers. This dynamic also increases the threat of participants dropping out and not completing the trial—a danger greatly exacerbated when the pool of eligible patients is smaller. These factors significantly increase the costs associated with rare disease trials.

Drug manufacturers must recoup their research and development investments and secure drug approvals to help patients and their bottom line. The importance of employing patient support strategies to enhance retention is critical. The patient experience is pivotal to completing clinical trials and sits directly at the intersection of the humanitarian mission and business motivation for drug development.

Benefits of Patient Centricity

For CROs and trial sponsors, understanding the patient experience is critical to advancing patient-centered trials. As our industry works to develop and define patient centricity in clinical trials, the overarching goal remains—to utilize the most effective tools to improve patient experience and deliver lifesaving treatments and life-enhancing products to market sooner.

Investing resources in patient experience programs benefits trial sponsors in several ways, including:

• Improving recruitment, retention, and diversity efforts: by reducing barriers hindering patients’ willingness to participate and remain in a trial.
• Getting lifesaving and life-enhancing therapies to market faster: making day-to-day aspects of the trial easier for patients results in fewer delays.
• Obtaining better data: an improved experience results in less stress placed on patients, mitigating the potential impact of stress on the integrity of trial data.
• Decreasing the likelihood of trial deviations: this reduces the risk of not securing the requisite approval for a drug to reach the market.
• Engaged participants: when patients feel included and supported during a trial, they feel their contribution is valued.

Throughout 2022, the FDA is releasing a series of guidelines with recommendations for how drug development programs can incorporate patient voices.{12} The message is clear: prioritizing patients’ social needs is equally important as caring for their healthcare needs.

The collective ability and willingness to put patient experience at the center of trial design is paramount to optimizing clinical trial outcomes. The industry is responding with patient-centric trial designs, involving patients earlier in the process and encouraging patient participation while mitigating risks and improving the quality of the research.

Outcomes improve when patients’ needs are considered and incorporated into early trial protocols. One study found drugs developed with patient-centric processes were 20% more likely to launch than those produced without them.{13} Placing greater emphasis on patients’ needs and concerns and improving communication results in increased patient satisfaction, reduced dropout rates, and a higher likelihood of trial completion.

The reasons patients drop out of trials range significantly and include fear, financial constraints, travel burdens, feeling underappreciated, health issues, work pressures, and more. Examining patient experience can offer insights into the many obstacles facing patients and caregivers.

Another benefit of patient experience efforts is the potential to lower participation barriers, resulting in enhanced patient diversity. Diversity among trial patients supports regulatory approval, as a high value is placed on enhanced diversity.{14}

Investing in Patient Experience

Understanding what creates a superior patient experience and prioritizing additional patient support as a strategic business objective offers an advantage in today’s complex and competitive drug development landscape.

Clinical trial teams can focus on what patients deem essential to their experience to generate better trial performance, such as faster recruitment or higher patient retention rates. In other words, the greatest returns come from addressing what matters most to patients.

To identify opportunities to improve patient experience, trial sponsors should determine pain points or missed expectations through analyses of trial patients. Clincierge recently commissioned an independent study of patients who participated in clinical trials; our research partner found that 95% of patients say they have “seriously” considered dropping out because of travel-related challenges.{15} Travel is also a significant barrier to participant recruitment and a clear pain point for nearly all patients surveyed.

Patients traveling to clinical trial sites commonly express concerns about being comfortable through flights, coordinating wheelchairs once they have landed, and finding accessible bathrooms and ground transportation able to accommodate wheelchairs. Caregivers flying with a disabled patient require extensive planning and coordination to book hotels and adequate local transportation. Parents face additional expenses when traveling with their children when travel costs are not covered or only covered for the trial participant.

Ongoing travel to and from clinical trial sites can have a ripple effect on patients and their caregivers, who suddenly face the pressures of missed work (and subsequent loss of income), time away from home and family, increased childcare needs, and financial burdens of travel.

These complexities intensify for patients and caregivers in rare disease trials, which typically involve additional pressures of foreign travel such as visas, relocation, language translation, housing, and transport of medically fragile (often pediatric) patients. It is understandable why nearly all patients consider dropping out of a clinical trial at some point due to the many challenges associated with travel.

The good news is trial sponsors and CROs can help mitigate any negative impact travel could have on trial retention by employing patient-centric strategies and patient support services programs to assist trial participants in navigating travel and managing reimbursement. From the patient’s perspective, these efforts are a leading consideration when enrolling or continuing their participation in a trial. In the aforementioned patient experience study, 100% of respondents said having a dedicated person to help them manage trial logistics was important.{15}

Providing patient support services throughout a clinical trial can minimize the additional pressures placed on patients and their caregivers to orchestrate trial participation. By employing patient care coordinators who manage logistics, including travel and reimbursement, patients and their caregivers can focus on the trial itself and the treatment provided, not the complicated logistics involved.

Conclusion

Patient retention and patient experience are inextricably linked. As the medical community sees the value in putting patient experience at the center of clinical trials, outcomes will improve for both patients and the industry. Improving patient experience expedites the process, making lifesaving and life-enhancing therapies available to more patients more quickly and allowing healthcare to maintain its original goal—caring for the health and well-being of patients around the globe.

References 

1. Bower P, Wallace P, Ward E, Graffy J, Miller J, Delaney B, Kinmonth AL. 2009. Improving recruitment to health research in primary care. Family Pract 26(5):391–7. https://academic.oup.com/fampra/article/26/5/391/635616#:~:text=However%2C%20research%20projects,of%20recruitment%20target)
2. Considerations for Improving Patient Recruitment into Clinical Trials. Clinical Leader. https://www.clinicalleader.com/doc/considerations-for-improving-patient
3. How to Improve Patient Recruitment in Clinical Trials? 2022. https://credevo.com/articles/2020/03/31/how-to-improve-patient-recruitment-in-clinical-trials/
4. Chaudhari N, Ravi R, Gogtay NJ, Thatte UM. 2020. Recruitment and retention of the participants in clinical trials: Challenges and solutions. Perspect Clin Res 11(2):64– https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7342338/#
5. Tufts Center for the Study of Drug Development. 2016. Assessment of Cost to Develop and Win Marketing Approval for a New Drug Now Published. https://www.globenewswire.com/news-release/2016/03/10/1187518/0/en/Tufts-Center-for-the-Study-of-Drug-Development-Assessment-of-Cost-to-Develop-and-Win-Marketing-Approval-for-a-New-Drug-Now-Published.html
6. Moore TJ, Zhang H, Anderson G, Alexander GC. 2018. Estimated Costs of Pivotal Trials for Novel Therapeutic Agents Approved by the US Food and Drug Administration 2015–JAMA Intern Med 178(11):1451–7. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2702287
7. Johns Hopkins Bloomberg School of Public Health. 2018. Cost of Clinical Trials for New Drug FDA Approval are Fraction of Total Tab. https://publichealth.jhu.edu/2018/cost-of-clinical-trials-for-new-drug-FDA-approval-are-fraction-of-total-tab
8. Moore TJ, Zhang H, Anderson G, Alexander GC. 2018, Estimated Costs of Pivotal Trials for Novel Therapeutic Agents Approved by the US Food and Drug Administration, 2015–2016. JAMA Intern Med 178(11):1451–7. doi:10.1001/jamainternmed.2018.3931 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2702287
9. Sertkaya A, Birkenbach A, Berlind A, Eyraud J. 2014. Examination of clinical trial costs and barriers for drug development. Submitted to: US Department of Health and Human Services Assistant Secretary of Planning and Evaluation (ASPE). https://aspe.hhs.gov/sites/default/files/private/pdf/77166/rpt_erg.pdf
10. New OCREVUS (ocrelizumab) data at ECTRIMS advance clinical understanding of underlying progression in multiple sclerosis. 2017. https://www.roche.com/media/releases/med-cor-2017-10-27
11. Gray S. 2021. Reducing Barriers to Participation in Clinical Trials for Rare Diseases. Clinical Researcher 35(6). https://acrpnet.org/2021/08/16/reducing-barriers-to-participation-in-clinical-trials-for-rare-diseases/
12. FDA Patient-Focused Drug Development Guidance Series for Enhancing the Incorporation of the Patient’s Voice in Medical Product Development and Regulatory Decision Making. https://www.fda.gov/drugs/development-approval-process-drugs/fda-patient-focused-drug-development-guidance-series-enhancing-incorporation-patients-voice-medical
13. The Economist Intelligence Unit. Patient-centric trials. https://druginnovation.eiu.com/patient-centric-trials/#:~:text=The%20analysis%20indicated,and%20rare%20diseases
14. Gray S. 2021. Diversity in Clinical Trials: Going Beyond Whyto  Clinical Researcher 35(3). https://acrpnet.org/news/clinical-researcher/
15. Clincierge. 2022. Amplifying Patient Voices in Rare Disease Clinical Trials. https://info.clincierge.com/vop

Scott Gray is the co-founder and CEO of Clincierge, a provider of patient support services for clinical trials. Since 2015, Clincierge patient coordinators have managed logistics and reimbursements in more than 300 clinical trials worldwide. For more information, visit www.clincierge.com.