Patient-focused Drug Development and Qualitative Methods in Clinical Trial

Almost 20 years ago, we introduced the qualitative methods in public health research in China. We organized the workshops and published the papers. We actually implemented the qualitative methods when we assessed the health care quality, KABP (Knowledge, Attitudes, Beliefs, and Practices) survey, and breast feeding research.

I have never thought that I would use any qualitative method since I am now a statistician and in the drug development field.  Last month, I attended a one-day interactive workshop “Clinical trial endpoints: methods and practice in developing measurements” with special emphasis on rare diseases. We spent majority of our time in discussing the qualitative methods (mainly the patient interview) to establish the content validity for patient oriented clinical trial endpoints (for example, the patient reported outcome (PRO)). For many orphan (rare) diseases, the characteristics of the disease may not be well defined and patient population in study may not be homogeneous. For the purpose of the clinical trials, it is challenging to identify a valid clinical endpoint to measure the efficacy. One approach to tackle this is to start with the patient. To interact with patients, the qualitative methods (for example the interview with patients) can be used to solicit the issues/items that are most concerned by the patients and hopefully we can based this information to derive a clinical endpoint for the clinical trials.

With patient-focused approach, the clinical endpoint should reflect the impact on:

• Patient’s mortality
• Patient’s function
• Patient’s feeling

This will be much different from the biomarkers which may not have any direct impact on any of these (at least in the short term). It is probably true that the non-disease specific tool for health related quality of life measure may be less sensitive and less relevant comparing to any tool / instrument / scale derived with the inputs directly from patients.

One thing has become clear that the clinical trial endpoint derived with the patient-focused approach need qualification (not the formal ‘validation’). Qualification process is supposed to be not as time consuming as the formal validation.  In 2010, FDA issued its guidance on “qualification process for drug development tools”.

In the newly passed PDUFA V (prescription drug user fee act), FDA proposed patient-focused drug development and a systematic effort in PDUFA V:

•  PDUFA V provides resources to support additional program staff to expand activities dedicated to providing review divisions with patient input
• FDA will convene meetings with participation from review divisions, the relevant patient advocacy community, and other interested parties
• FDA will hold four public workshops per year – a total of 20 meetings over 5 years. Each meeting will focus on a different disease area, reviewing the armamentarium for that indication, and identifying areas of unmet need.

FDA had already put this in action and organized its first meeting last Month to discuss the list of diseases to be included. The background and the plan about the patient-focused drug development program are described in the presentation by Dr Mullin.