During the question and answer session, we find out exactly what clinical trial success means and how to achieve it.
OSP: What elements of design help set up a clinical trial for success?
Creating a well-designed and reviewed protocol is critical to the overall study’s success. The clinical study protocol details study background, rationale, product information, required data collection and study processes to support answering the research questions. Best practices on how a protocol can be designed include the following:
Consider establishing a scientific advisory board to consult on the aims and statistical design of the proposed study. Ideally, this committee convenes prior to formal protocol development to guide study design up-front for center acceptance and post-study for practice implementation.
- Include only critical eligibility criteria to both generate the largest pool of subjects to participate and to allow results to be as generalizable as possible.
- Design the subject visit schedule to align to standard-of-care. This approach reduces the burden on both the site to create specific clinical trial process and the subject who can avoid extra trips and assessments.
- Ensure the protocol does not collect extraneous data that requires effort to collect and analyze but is then not utilized. Taking this step reduces the study budget and labor burden.
- Invite a broad set of stakeholders to review the protocol to understand impacts from all angles. Beyond core protocol team members, valuable voices include those of the patient or advocates, center PIs, research coordinators and laboratory partners.
OSP: How do we assess and mitigate risk when designing a clinical trial?
Risk mitigation is ideally centered within the protocol development process. Many sponsor organizations and CROs require completion of risk sections in the protocol and project management plan templates. Key study stakeholders must not only own operational area content, but they must also identify risks and propose mitigation solutions for holistic quality oversight.
For example, the quality function assesses regulatory strategy to craft an audit schedule to prepare for potential inspections. Ensuring knowledgeable personnel own risk mitigation is key. The sooner risk identification occurs, the sooner plans can be implemented for mitigation, ultimately leading to a trial run more safely and efficiently.
OSP: What are current barriers for sites to participate in clinical trials and how do we mitigate them?
Primary site barriers to participation on clinical trials include constraints associated with budget, personnel, and available patient populations.
For myriad reasons, site budgets may be insufficient to cover research costs. Studies funded through grant mechanisms are often stretched thin, and invited sites may need to determine feasibility of subsidizing portions of their own efforts for the good of the research question.
Additionally, resourcing and retention struggles within hospital clinical trial offices are well-documented as a barrier for site participation or delayed start-up. When assessing sites for participation, sponsors should include a strong rationale document.
Lastly, centers may want to participate on a trial but either do not have the patient population to attract trial opportunities or are already committed to other trials that directly compete.
OSP: What are current barriers for patients to participate in clinical trials and how do we mitigate them?
While many patients theoretically understand benefits of clinical trial participation, they may decline involvement due to lack of transparency or trust in the medical community. Patients also encounter financial, cultural, and logistical barriers that prevent initial and ongoing participation.
The first formal trial contract for a patient is via the informed consent process. The Informed Consent Form (ICF) conveys trial background, risks, benefits and the patient’s expected experience.
Other barriers patients experience include financial, logistical and lack of support. These barriers can be mitigated by compensating patients for travel expenses beyond standard-of-care and for time spent answering patient-reported outcomes questionnaires. Organizing transport may also incentive a patient to participate. Lastly, researchers should close the loop on the trial by ensuring patients receive the results of the research study so they can understand how they have impacted the scientific question.
OSP: What sponsor-led processes do sites find most helpful when implementing new clinical trials?
Clinical research sites are busy, and the key to implementing a new clinical trial quickly is to make the site’s job easier. Sponsors can do this by offering solutions that streamline sites’ activities without overly disrupting standard site processes. Therefore, the sponsor should provide options sites can adapt to fit their needs.
Site personnel should be present at the site initiation visit and be fully engaged during protocol training. Site staff are however often pulled away for other obligations, and training may need to be conducted at different times.
OSP: How can the voice of the patient be incorporated into clinical trials?
The voice of the patient is essential in clinical trial design to ensure the patient perspective is considered during the development of new treatments. Patient engagement should be an ongoing process throughout the entire clinical trial journey.
These boards provide valuable insights that allow sponsors to understand the patient experience and make more patient-centered decisions. Through the advisory board, patients and caregivers can actively engage in the planning, design and conduct of clinical trials. The boards can also review patient recruitment materials and trial processes to ensure they are patient friendly.
OSP: How can we make clinical trial participation easier for patients?
Recruiting and retaining a diverse range of participants is one of the biggest factors in a clinical trial’s success and currently one of the biggest challenges in the clinical trial industry. Making participating in clinical trials easier for patients is crucial to support recruitment and retention activities. Some patient-centered strategies include the following:
- Clear and Accessible Informed Consent Process: The informed consent process should be patient-friendly and clearly explain the trial purpose, procedures, potential risks and benefits. Electronic consent can be more convenient for patients to provide their consent, include videos to explain the study or research in general, and can be used to assess patient understanding.
- Patient-Centric Trial Design: Trials should be designed with patient convenience in mind. During protocol development, sponsors should collaborate with clinical staff at sites to understand standard of care procedures and design the protocol-required assessments to align with the standard of care. This ensures patients do not need to do extra visits or assessments.
- Patient Support and Education: Sponsors and sites can collaborate to provide support and education to patients throughout the trial by offering educational materials and resources to help patients understand the trial processes and their role in research.
- Trial Result Dissemination: After clinical trial results are available, Sponsors should develop summaries explaining study results in lay terms and provide these summaries to participants. Taking the time to share trial results makes patients feel appreciated and that their trial participation contributed to greater scientific knowledge.
OSP: What is the best way to support a research center throughout the conduct of a study?
Treat them as a trusted partner and provide excellent customer service. To accomplish this, study teams should create real connections, develop a communication strategy, and constantly search for ways to reduce site effort.
Sponsor or CRO personnel should focus on creating real connections with site staff. This can be accomplished by approaching site staff with empathy and assuming positive intent.
Ways should be found to reduce site effort. During protocol design, sponsors should collaborate with sites to develop a well-designed study protocol that aligns with the site’s standard processes and is feasible for sites to operationalize.
OSP: How can we design a clinical trial to be accessible and attractive to a diverse set of patients?
The FDA has recently issued draft guidance acknowledging the need for clinical study enrollment to reflect the diversity of the country’s population. To accomplish this goal, a variety of recruitment strategies should be considered and documented, when applicable in a Race and Ethnicity Diversity Plan. Beyond ensuring eligibility criteria are not specifically restrictive to certain patient populations, how patients are approached should be considered. Consider methods that identify people that are not yet patients.
Besides centrally recruiting patients to trials, a critical step for study teams is to select centers with known ethnically diverse patient populations. Also, consider whether a full or partial decentralized clinical trial model can be utilized as this could attract patients that have little flexibility for multi-hour clinic visits.