From researchers to sponsors to patients to advocacy groups to clinicians, rare disease research is full of passionate, driven, and determined people. As the greatest asset to the field, all people involved must be utilized to their greatest potential for a study to be successful. That’s why significant attention must be paid to the operational challenges within rare disease research.
For studies in support of orphan drug designations, these operational concerns can be broken down into five major issues: patient identification, patient engagement, patient retention, investigative site selection, and site team support. Additionally, within rare disease, researchers frequently work with pediatric populations and older populations requiring caregivers, which adds yet another layer of complexity to the mix.
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1. Identifying Patients
Although many of the same strategies for more common conditions can work for some conditions, remember that the key word in “rare disease” is rare. Sponsors and CROs must work with smaller patient pools and may need to utilize additional tools to reach out to patients. Whereas more common conditions have well-established clinics to tap, keep in mind that only five percent of rare diseases are being treated.
Medical informatics has helped to change the way orphan drug developers do study recruitment. Site databases, feasibility assessments, in-depth reviews of disease populations, standards of care for target populations, and other data can help researchers make more informed recruitment decisions.
Likewise, talking with key opinion leaders and tapping patient registries are other great resources. Patient advocacy groups, in particular, are becoming more involved in research today and have been bolstered by regulatory changes. Leveraging relationships with appropriate advocacy organizations dedicated to supporting patients and their families can provide insights into the unique challenges each patient population faces. This information can, in turn, be used to tailor study designs and operations to suit particular needs. Recruiting the right patients for your particular study is an important method of boosting patient engagement and preventing attrition before the trial begins.
2. Engaging With Patients
The most important aspect of patient engagement is to give study participants a voice. This means walking in their shoes and considering their perspectives. Too many opportunities are missed when researchers fail to listen to patients’ insights and perspectives.
Tailoring communications is also a vital part of patient engagement. Ensure that patients understand what it means to participate in a clinical trial, including the realistic risks and benefits of participation. A major part of this is understanding consent and assent procedures. For pediatric trials, this may include being able to explain this information to parents and guardians in a way that they understand and can, in turn, relate important points to their children.
Other important communication strategies to consider (and possibly tailor where appropriate) include:
- Patient outreach materials
- Referrals and referral materials
- Branding and advertising
- Social media
3. Retaining Patients
Orphan drug designation trials work with smaller sample sizes, making each and every patient vital to the statistical validity of the study results. Consequently, patient retention is a special concern in rare disease research. Make sure you’re putting patients first by:
- Clarifying the commitment to participate
- Providing participation packets
- Understanding patient and family commitments (both school and work) — remember that patients have lives outside the clinic!
- Providing travel and accommodations for families and caregivers, especially for studies of exceptionally rare diseases — many patients may travel a long way to reach a study site (or to access care in general).
- Updating patients and families periodically on the study’s progress
- Acknowledging contributions with thank-you notes and similar gestures
4. Selecting the Right Sites for Your Study
Proper study selection is always crucial for drug development success. For rare disease research, “go where patients are” is a deciding factor and often includes international study sites. When choosing study sites, be mindful of:
- Local regulatory submission requirements
- Good clinical practice (GCP) standard of investigators and monitors in a specific country
- Travel restrictions, including those that may be imposed by the condition being investigated
- Import/export license requirements
- State of the country, such as its political landscape, recent natural disasters, and ongoing civil unrest — be wary of signs that local instability could interrupt or otherwise negatively impact the study
- Research experience (or a lack thereof) — provide necessary training and support to ensure study compliance
- Technical capabilities — make sure the site has the appropriate equipment to conduct the study
- Local regulations for Investigator Meetings participation
5. Engaging and Supporting Your Site Teams
Site team training should be continuous but special attention should be given at the Site Qualification Visit, Site Initiation Visit, and Investigator Meetings. Additional GCP training when required is also key, especially when patient compliance is an issue. Site staff should be provided with clear and comprehensive study manuals.
Sponsors and CROs should keep up regular communications with study sites where updates can be shared and feedback is invited. Also, support for database reviews is a key part of ensuring data integrity.
Additional specialized certifications for study staff should be considered. As an example, Premier has created internal multi-module certifications specifically for both rare diseases and pediatrics. All staff assigned to these cases must complete this training, which is recorded in our education tracking system.
Quality monitoring for critical thinking skills should also be routine. For studies involving unusual or complex indications, experience monitoring of site staff can be useful.
Additionally, succession plans for staff transitions are crucial, yet often overlooked. While prioritizing sites with low staff turnover rates is important, some changes are inevitable. Make sure to be prepared with procedures in place to prevent major disruptions to the study.
Effectively Operationalize Your Next Orphan Drug Trial
The good news? Each of these operational concerns can be addressed with a well-established network of clinical sites and the experience they bring to the table. Contract research organizations, like Premier, offer clients a strong international network of monitors and project management professionals, as well as regulatory, data management, statistical, scientific, and medical experts.
To learn more about the importance of having a well-established network of clinical sites in rare disease drug development, make sure to watch our recent webinar Improving Regulatory and Operational Performance in Orphan Drug Development.