Rare disease trials require effective participation support strategies to succeed
ICON is leading the way in rare disease clinical research having supported 779 rare disease clinical trials in the past five years. Every day, thousands of colleagues at ICON work tirelessly to support the success of rare disease clinical research – because patients can’t wait.
Rare Disease Day invites all of us to understand and uplift the 300+ million people affected by rare diseases, to celebrate incredible achievements and to share in the continuing fight for progress. Advancement towards more meaningful treatments and cures requires successful clinical trials. There are no successful trials without participants.
This Rare Disease Day, we encourage you to learn more about the barriers people affected by rare diseases face in taking part in clinical research, why they are important risks that require mitigation planning, and the strategies that can reduce and eliminate them. We invite you to join us in making clinical research more accessible and less burdensome for them.
Understanding participation barriers and trial success
An analysis conducted in 2012 of discontinued clinical trials (industry-wide, across rare and non-rare indications) suggests 55% are discontinued due to recruitment failure alone, making it the single highest cause of trial discontinuation behind lack of product efficacy (15%) and adverse events (11%).1 Recruitment failures were also a leading cause of trial delay – more than 80% of trials were delayed due to recruitment failures.2
These figures point to recruitment failure as the key risk facing a clinical stage sponsor regardless of the indication and to the need to develop a sound participation support strategy to mitigate this.
Urgency in rare disease
Rare disease trials often impose higher demands on participants than prevalent disease trials. Few trial sites per country is typical due to low levels of expertise in rare diseases across health systems, often requiring patients and caregivers to travel longer distances to participate in clinical research. Protocols are typically highly demanding of participants, often requiring them to undergo extensive, invasive, and frequent assessments, particularly for early-stage studies. Some study requirements which may appear innocuous to a protocol writer, may have highly burdensome implications for a rare disease patient whose daily experience is complex and not well understood.
There is also ample evidence that living with a rare disease often deeply impacts individuals and families financially, physically, and psychologically – making it challenging to absorb incremental financial, physical and psychological impacts imposed by clinical trials.3, 4, 5 These are compounded for individuals experiencing intersectionality of rare disease and racial, socioeconomic, disability and other factors associated with societal and healthcare inequity.
Sponsors wishing to safeguard the success of their programme shouldn’t equate urgency and severity of unmet need in rare disease with ability and willingness to do anything and everything asked during study participation. Motivation simply does not trump pragmatic financial, physical, and psychological considerations.
Industry-wide enrolment rates for select Duchenne muscular dystrophy trials conducted over the past decade illustrates this well. Despite controlling for relevant factors like DMD participant age, site location, study design, and other details known to impact enrolment in the analysis below, there is a clear downward trend in this competitive research space notwithstanding a highly motivated patient community with highly sophisticated patient organisations championing and driving research throughout. This demonstrates that for sponsors, it is critical to anticipate and develop strategic risk mitigation plans early during clinical design stages.
How sponsors can mitigate risks of recruitment failure in their rare disease clinical programmes
Sponsors can mitigate risks of recruitment failure by:
- Understanding participation burden and how it drives risk within a clinical programme
- Taking a quality by design approach
- Learning about the broad range of participation support strategies available and their budget impacts as early as possible in study development
By understanding and prioritising risks of recruitment failure as early as possible, sponsors can help ensure the success of their clinical programme development.
To help sponsors do this, ICON conducted key primary research with many rare disease patient populations on the barriers to participation in rare disease trials and the support services they need to enrol and remain in studies. The results of our first-of-its kind, primary research were presented at NORD 2021 and a detailed summary was published in our whitepaper, ‘Crossing the Finish Line Why effective participation support strategy is critical to trial efficiency and success in rare diseases’.
Furthermore, sponsors can familiarise themselves with the wider evidence base on trial participation success.
Take a quality-by-design approach
Incorporate recruitment failure risk assessment and mitigation strategy into the early stage of the study design process. Ideally, in parallel to draft protocol concept development and long before a protocol is finalised. This helps to identify mitigations that may be ‘baked into’ the study design. Example considerations include questions such as:
- Can some services be delivered to patients at home or not?
- Does willingness to enrol increase if some exploratory endpoints are trimmed or added?
- How easy or difficult do patients think it will be to maintain stable background therapy?
A quality-by-design approach typically involves a sponsor engaging with the key rare disease patient organisation(s) serving the target patient population and conducting qualitative research with patients to understand the unique constraints they may have and how feasible and acceptable different aspects of your planned clinical study (eligibility criteria, assessments, study site locations, etc.) may be to them.
This can provide sponsors with very rapid, valuable guiding insights and generally has very low costs, making these activities some of the highest ROI in terms of potential impact to study success.6 One analysis found that rare disease studies designed with a quality-by-design approach to participation support recruited four times faster than rare disease studies that did not; another found that a quality-by-design approach may contribute to reaching commercial stage up to two quarters faster.7,8
To help sponsors take a quality-by-design approach ICON has:
- Developed a free, rapid, easy-to-use, validated Toolkit. ICON’s Rare Disease Patient Centric-Clinical Trial Development Toolkit comprises the widely used Patient-Centric Protocol Risk Assessment Tool V2.0 along with other resources to help guide sponsors through assessment and strategy development activities.
- A dedicated Rare Disease Patient Advocacy Strategy team of highly seasoned experts adept at guiding collaboration between sponsors and Rare Disease patient organisations, serving as a resource for sponsors without in-house expertise or capacity, particularly smaller biopharmaceutical companies in critical early stages of development.
- Patient Insights and Patient-Centered Outcomes teams who provide a range of qualitative research services to help sponsors understand the lived experience of their target patient population and the key barriers they may face to study participation.
Know your participation support strategy options early
While a broad and growing range of participation support solutions exists, sponsor teams are often unfamiliar with all their options.
A few examples of services that address practical barriers to participation for rare disease patients and caregivers include:
- Navigator/concierge service – a navigator is a person whom the patient can reach out to by phone any time throughout the screening period and/or study period and serves as a resource for questions, trouble shooting and adherence support.
- Prepaid cards –there are costs related to trial participation, such as hospital parking fees, food and hotel stays, that many patients can’t absorb and wait for reimbursement. Offering prepaid cards can meaningfully impact many individuals’ abilities to participate.
- Two caregivers – a frequently used strategy to remove barriers to participation where a patient may need round the clock support is to budget for two caregivers to accompany the patient so each can take breaks, sleep and know their loved one is supported.
- Childcare assistance –childcare costs for a patient’s siblings, or children while their parent/caregiver accompany patients in the trial is often a key barrier for many families affected by rare diseases that can often make it impossible to take part in a study.
- Flexible accommodation type – different types of accommodation may be more feasible for patients and caregivers at different stages of a study. The need may shift from hotel to Airbnb to in-hospital. Allowing participants flexibility throughout a study as their circumstances shift reduces barriers to participation.
- Private transfer – arranging a driver rather than relying on caregivers and patients to do the driving, use public transport or find a friend who can drive them can make a significant difference to ability to take part and stay in a trial.
Sponsors can gather information about these strategies and their costs early on in their clinical programme planning by inquiring about these with service providers long before study request for proposals (RFP) are sent. Many providers are willing to discuss their services with sponsors and provide “ballpark estimates”. Obtaining these early on can help a sponsor approach their RFP rounds more efficiently and with a more focused study risk mitigation strategy.
To help sponsors do this, ICON is proud to offer an industry-leading range of participation support solutions that aim to reduce trial participation burdens for rare disease patients and caregivers.
Progress is only possible with rare disease patients and caregivers
ICON is deeply committed to providing strategies and tools that enable sponsors to reduce the burden of participation for patients and caregivers. Our dedication arises from our responsibility as a leader in rare disease clinical research and from our dedication to our loved ones, friends and colleagues affected by rare diseases.
We know that progress towards meaningful cures and treatments is only possible with participation from rare disease patients and caregivers. Join us in making rare disease clinical research less burdensome and more accessible for them.
Contact us to learn how we can help reduce the burden of participation for patients and caregivers in rare disease clinical trials.
Authors
Laura Iliescu, MSc
Jana Benesh, PhD
References
1 Pharmaceutical Technology Enrolment Issues are the Top Factor in Clinical Trial Terminations. 2018. Dec 05, [Last accessed on 2024 Feb 05]. Available from: https://www.pharmaceutical-technology.com/analyst-comment/reasons-for-clinical-trial-termination/?cf-view
2 Clinical Trials AReNA: Clinical Trial Delays: America's Patient Recruitment Dilemma. 2012. Jul 18, [Last accessed on 2024 Feb 06]. Available from: https://www.clinicaltrialsarena.com/features/featureclinical-trial-patient-recruitment/?cf-view
3 Angelis, A., Tordup, D., Kanavos, P. (2014) Socio-economic burden of rare diseases: A systematic review of cost of illness evidence. Health Policy, 119(7), pp. 964-979.
4 von der Lippe, C., Diesen, P.S. & Feragen, K.B. (2017) Living with a rare disorder: a systematic review of the qualitative literature. Molecular Genetics & Genomic Medicine, 5(6), pp. 758-773
5 Naidoo N., et al. (2020) The research burden of randomized controlled trial participation: a systematic thematic synthesis of qualitative evidence. BMC Medicine, 18(6), https://doi.org/10.1186/s12916-019-1476-5
6 Stergiopoulos, S. et al. (2019) Measuring the Impact of Patient Engagement and Patient Centricity in Clinical Research & Development. Therapeutic Innovation & Regulatory Science, DOI:10.1177/2168479018817517
7 The Economist (2018) The Economist, Intelligence Unit: The Innovation Imperative: The future of Drug Development, Part I: Research Methods and Findings
8 Levitan, B et al. (2019) Assessing the Financial Value of Patient Engagement: A Quantitative Approach from CTTI’s Patient Groups and Clinical Trials Project. Therapeutic Innovation & Regulatory Science, 52(20), pp. 220-229.