The US Food and Drug Administration (FDA) recently issued guidance, Patient-Focused Drug Development: Methods to Identify What Is Important to Patients, which identifies additional requirements to satisfy the agency's approach to accepting patient reported outcomes as a basis for drug or medical device approval. FDA has been loath to base drug or device approvals on subjective criteria that cannot be verified by physicians, may not reflect objective measures of disease severity, or for which the improvement or scaling may be dependent on the individual.

In 2016, in § 3002 of the 21st Century Cures Act, Congress directed FDA to develop and agree to patient-focused methods to assess drug efficacy.

FDA's (and other international medicinal product regulatory agencies) resistance to use of patient reported outcome measures (PROMs) has been based on whether those endpoints or outcomes could meet the agency's objective to avoid bias an important issue in assuring the validity of clinical trials. This contention that, first, there may be difficulty in training patients to provide accurate and reliable information on disease severity that is comparable to other patients. And, second, that improvements from one level of severity to another might be so subjective that the drug effect would be distorted by who was enrolled or how patients were instructed to report or which patients were reported and how they individually viewed the severity of their illness. While these views might be valid statistical concerns, the prior focus was thus directed toward physician's view of patient illness rather than the patient's own view of their illness.

FDA accepted some largely highly traditional scores the 10 point pain scale that uses increasingly severely affected cartoons of facial expressions and a score reflecting Activities for Daily Living (ADLs). ADLs include 12 self-assessment such as the ability to eat, dress or bathe oneself.

To obtain approval of a new patient reported outcome measure, therefore, FDA had required "validation" of the scale in a separate or independent study from that reflecting drug effect. Validation was intended to show that a one- or two-step change in outcome was consistent across numerous patients and that baselines were in line with disease severity or burden measured objectively. These additional studies were expensive, delayed drug development, and essentially provided competitors with free data and scores for their own drug development.

In October, FDA issued the second of two Guidances mandated by the 2016 Act. The new guidance could be interpreted to add complexity to the development of patient reported outcome measures. The new and additional requirement now includes obtaining preliminary patient input on the measures including:

  • Generate and document in-depth information about patient's experiences, perspectives, and feelings to identify the specific outcomes that would be relevant to all patients.
  • Use pre-defined survey instruments -- structured or open-ending patient interviews or focus groups.
  • Analyze the resultant data using a formal data analysis tool.

These initial development methods would then, presumably, be subject to the same post-development validation requirements that have historically been applicable to any newly developed patient reported outcomes that were set forth in guidance issued in 2009.

One aspect that is not discussed is whether the tools developed can be maintained as proprietary under various forms of intellectual property protection. Navigating this new guidance will require experience in how other companies have addressed FDA concerns a benefit of an outside consultant with prior experience in the pitfalls and pearls of negotiating with FDA on such complex issues. A common but unfortunate issue that we have encountered is that approaching FDA without a thorough knowledge of agency issues can be fatal to, or delay, progress. Here at Baker, we have precisely this cross-division and historical experience that may be of value to a company attempting to develop such tools. Individual teams in industry may have experience in one disease area but may not bring that type of experience or understanding of agency rationales. Over the years, we have had the opportunity to be involved in the development of several patient reported outcome or subjective scales in various fields across divisions. The tools described by FDA are frequently used in other areas such as the development of cosmetics or other consumer goods. We look forward to the opportunity to assist you in understanding the requirements, supporting your development plans, and protecting your intellectual property.

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