FDA Standard Core Clinical Outcome Assessments and Endpoints

Notice Number: NOT-FD-18-014

Key Dates
Release Date: July 31, 2018
Response Date: October 15, 2018

Related Announcements
RFA-FD-19-006

Issued by
Food and Drug Administration (FDA)

Purpose

FDA is seeking information submissions from the public.  Information is being solicited to inform planned work to promote development of publicly available standard core sets of Clinical Outcome Assessment (COA) measures for specific disease indications. A core set would reflect measures, tools, and endpoints that assess a minimum list of impacts that matter most to patients and are likely to demonstrate change relating to disease burden, treatment burden, and, if applicable, physical function. 

The information requested may be used to structure a program to facilitate the development of publicly available core set(s) of COA measures and endpoints.  Under the envisioned program qualifying third parties would conduct a well-managed, transparent, and methodologically sound process following a development protocol that provides for: 1) Consistent application of appropriate methods for COA set development applying new FDA patient-focused drug development methodological guidance as appropriate; 2) Consideration and use of publicly available measures that have already undergone extensive vetting whenever possible;  3) Publication of interim work products at each milestone in the COA set development process to make them publicly available for all stakeholders to review, comment, and utilize; and 4) Engagement of key stakeholders from the patient disease advocacy community, FDA medical product reviewers, regulated medical product industry, government and academic researchers, health care providers, health technology assessors and health payers, and others, at key milestones via public meetings and workshops, to ensure that identified concepts, measures, tools, and endpoints reflect what is most important and relevant in stakeholder decision making.

Background

Since 2012 FDA has been conducting patient-focused meetings in different disease areas to hear directly from patients about the impact of disease on their daily life, and the burden of current treatments.  Patient experiences are providing new insights for FDA reviewers and reinforce the importance of incorporating the patient’s experience to inform drug development.  This includes not only the clinical context for FDA decisions, but more direct evidence regarding drug benefits and risks.  This can be achieved when methodologically sound COA measures, tools and endpoints that are developed and deployed in clinical trials provide evidence for FDA decision making that can be incorporated in drug labeling to better inform decisions by doctors and patients at the point of care. 

However, there is currently very little coordination of development of these COAs across all the diseases that need them.  The separate independent efforts by different patient advocacy groups and drug sponsors within and across disease areas are resulting in a diversity of measures and proprietary COA tools that create a continued “learning curve”, a higher level of investment by these groups, and fewer opportunities for streamlining than would be best for long-term sustainability.   Repeated significant start-up costs and varying levels of experience among sponsors, advocacy groups, and the consultants they may engage, may lead to variable quality in the resulting COA related endpoints.  Inconsistent quality in COAs both limits their value to decision makers and can potentially undercut confidence in these data.  These challenges can discourage company investment in obtaining the patient’s perspective and experience to inform decision making despite the potential to improve development and delivery of treatments for patients. 

Information Requested

FDA is interested in the identification of disease and treatment impacts that matter most to people living with a disease or condition.  In addition, of those impacts, FDA has a focus on ones that can be addressed or ameliorated by the medical technology under development or that could in the future be submitted for FDA review and potential marketing approval.

  1. If currently available measures do not fit the topics, concepts, or wording patients identified for a given disease area based on recent patient input—for example the words or time frame used to describe fatigue or pain may be different than wording in available measures—how would you efficiently address this?

To minimize ambiguity and uncertainty for both regulatory decision makers and medical product sponsors, FDA is not only interested in the high-level concepts (e.g., pain, fatigue) related to those impacts but also interested in the set of specific measures and tools and exact endpoints that are proposed to be used for a given disease.

  1. What if the already established concept is more general and does not specifically tie to a tool or specific endpoint targeting the impact that a new drug would potentially have on this concept—how would you address this?
  2. What if a measure or tool is available for an identified concept, but it is more general and not specifically targeting the impact that a new drug would potentially have on this concept—how would you address this?
  3. What if a tool is available but has not been tested in the disease population under study—how would you address this?

To ensure acceptance by regulatory and other authorities the measures, tools, and endpoints need to have sufficient reliability, and validity for the anticipated patient population. 

  1. For a given disease area, what approaches can be taken to engage multiple authorities (e.g. international regulatory bodies, HTAs) and other decision makers (e.g., professional societies, research organizations, clinicians, regulated medical product industry) to gain needed input and ultimate acceptance of the same standard core set—while minimizes overall reporting burden for patients living with that disease?

To ensure widespread adoption and system uptake, measure sets, tools, and endpoints need to be decision relevant, understandable, readily accessible and affordable, and become familiar to all users.

  1. What if publicly available measures and tools are not as good of a fit compared to a proprietary measure set that is licensed to those able to pay a more-than-nominal fee and accept the terms specified by the license holder—how would you approach this? 

Most drug development programs are multinational and multiregional in the conduct of clinical trials and their intended markets.  The measures, tools, and endpoints need to be relevant and applicable across regions and variations in culture and ethnicity of patient populations and the technology and infrastructure available to support clinical research and clinical care.

  1. What would you do to determine the applicability of a measure or measure set and scoring developed in one region of the world to patient (likely clinical trial) populations in other regions (e.g., across all regions now represented by ICH regulatory members and observers)?  What types of issues might arise that suggest limited applicability or operability?  What would you do to address such issues that indicate limited applicability or operability?

For most diseases, the patients who seek treatment may range in age.  They may also range in level of literacy, levels of cognition, disease severity, and other dimensions that may affect their ability to report or otherwise reliably participate in data collection.   The measures, tools, and endpoints that are developed and used need to recognize and address these important variations in the patient population.

  1. For a given context of disease and patient subpopulation:
    1. How would you identify the limitations of existing measures and tools?
    2. What sort of limitations would you anticipate may be identified?  Please offer some examples based on your previous experience.
    3. For the various types of issues identified, what would you do to address these limitations?  What has been your experience with the effectiveness of these strategies in the past?
    4. Considering experiences with studies with pediatric patients—for a given disease or condition and patient age group-- what has been your approach to reporting:  who does the reporting for the patient (and why), how is the reporting collected?  When?

Based on your prior work and experience with development of COA measures, tools and endpoints:

  1. How much time does it take (elapsed time of the project from start to finish) and how much does it cost (estimates of both the US dollar amount and level of effort would be helpful) to test and modify an existing measure set or tool?
  2. How much time does it take (elapsed time of the project from start to finish) and how much does it cost (estimates of both the US dollar amount and level of effort would be helpful) to do “from the ground-up” development and testing of a new measure set or tool?
  3. What are the expertise and operation management skill sets needed for the work described in this RFI?
  4. What should the maintenance lifecycle for measures, tools, and endpoints be? Describe example recommended maintenance plans.
  5. What organizations are currently using clinical outcome assessments for decision making? What information do they use to inform their decision making, and how is it used?
  6. What steps can reduce patient and other informants’ burden?

Responses to Questions 1 – 14: 

Responses to this RFI should include some of the following information:

Provide information and perspectives in response to the questions listed above.  Please use numbering that corresponds to the question numbering specified above and adhere to the page limit (5 pages total).   Please note that it is not necessary to cover all the areas. In addition, it would be helpful if examples of successful or failed lessons learned are included.

Confidentiality

Responses to this RFI are voluntary but encouraged.  Any personal identifiers (e.g., names, addresses, e-mail addresses, etc.) will be removed when responses are compiled.  Only the de-identified comments will be used.  Proprietary, classified, confidential, or sensitive information should not be included in your response.  The Federal Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s).

This RFI is for information and planning purposes only, and should not be construed as a solicitation or as an obligation on the part of the Federal Government to provide support for any ideas identified in response to it.  Please note that the Federal Government will not pay for the preparation of any information submitted or for its use of that information.  Responses will be compiled and shared internally with FDA staff and its science councils, with one or more subcommittees of the councils, and with FDA scientific working groups, as appropriate.  In all cases where responses are shared, the names of the respondents will be withheld.

Inquiries

Please direct all inquiries to:

Shashi Malhotra
FDA/OFBA/OAGS
Telephone: 240-402-7592
Email: Shashi.Malhotra@fda.hhs.gov