Gathering Clinical Evidence In Orphan Indications

Given the very small patient population and even smaller number of investigators associated with clinical trials in orphan indications, every research participant and every piece of data is critical in building the required clinical evidence to support new drug treatments. To accomplish this objective more easily, sponsors should consider the many advantages of starting this process as early as possible, for example with the first natural history studies, as well as by designing and launching longer-term, prospective observational studies or patient registries.

From the very beginning, a natural history study enables sponsor companies to assess the clinical research infrastructure at the probable investigational sites and implement any corrective actions - e.g. providing additional GCP training, confirming an understanding of, and an ability to, conduct the required diagnostic or clinical assessments or identifying any hurdles to patient participation – to ensure high quality data prior to the initiation of Phase 2 and Phase 3 clinical trials.

As my colleague, Mark Harnett, stated in Biostatistics’ Challenges in Orphan Indications:

…one of the key aspects of any orphan Investigational New Drug application is the discussion of the proposed endpoints to be used in the program and the determination of the appropriate regulatory pathway.

Mark describes how a natural history study at the pre-IND stage can help identify potential endpoints or surrogate markers and to describe the course of the orphan disease in the target patient population. In addition to better informing the clinical development plan, a natural history study can be the foundation for a number of other activities to gather the clinical evidence required by broader groups of health care delivery stakeholders to support the approval, launch, and acceptance of a novel orphan drug treatment. Many times, a natural history study may also serve as a template for a prospective patient registry to continue gathering important clinical and patient reported outcomes in parallel to the clinical trials.

Clinical trial protocols have rigid inclusion and exclusion criteria, clinical endpoints, and assessment schedules that are focused squarely on obtaining meaningful clinical results to support regulatory approval. Even within a rare disease indication, however, there will be patients and physicians who do not transition from the natural history study to the clinical trials – either due to the patients not meeting the trials’ inclusion/exclusion criteria or to unmanageable geographical barriers. A concurrent, prospective patient registry can keep these patients and physicians engaged in disease research and enable them to collect important “real world” data that can contribute to the clinical development plan, as well as support launch and post-approval activities to satisfy the needs of patients, physicians, reimbursement agencies, and regulatory authorities.

For example, a patient registry can help better define patient referral and diagnostic pathways, patient preferences, cost of illness, and quality of life attributes. Relationships with key opinion leaders and other treating physicians can be strengthened by reviewing registry data and publishing important findings, paving the way for updated disease management and treatment guidelines. This information can help build the product’s value proposition and guide market access strategies. Finally, a well-designed and managed patient registry can be the framework for anticipated post-approval mandates from the FDA or EMA.

Rely on NovusLife to help you develop and implement the clinical evidence strategies required to support the development and launch of your orphan drug product or other drug treatments for patients with unmet medical needs.

Neal Mantick is a Principal Consultant, Clinical Evidence at NovusLife with nearly 20 years of experience in directing observational research and commercialization programs withbiopharmaceutical drug and device products for patients with unmet medical needs.

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