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FDA’s Clinical Outcome Assessment Compendium

FDA’s Clinical Outcome Assessment Compendium

CDERConversations 715pxElektra Papadopoulos, M.D., MPH

Talking to Elektra Papadopoulos, M.D., MPH, Acting Associate Director, Clinical Outcome Assessments Staff, Office of New Drugs, CDER, FDA

As part of its effort to foster patient-focused drug development, FDA’s Center for Drug Evaluation and Research (CDER) is announcing the publication of a compendium of clinical outcome assessments (COAs) to promote the use of patient-focused outcome measurement in drug development. CDER is seeking public comment on the pilot version of this compendium, including its potential use as a communication tool as well as its overall content and format.   

Let’s start off with the basics.  What is patient-focused outcome measurement about?

Patient-focused outcome measurement starts with an understanding of the impact of a disease on the people who have it, and what they value most in terms of alleviating symptoms. This information can then be used to develop tools  that assess the things that patients most care about. Patients and prescribers need meaningful information about a drug’s benefits and risks to make important treatment decisions. Patient-focused outcome measurement is really about measuring things that are important to patients, such as how a treatment will affect their symptoms, day-to-day functioning and overall survival.

How does patient input influence the choice of outcome measures in drug development?

Selecting the right outcomes to measure is a very important aspect of drug development. Patient input into the selection of outcomes that are meaningful to them can profoundly influence drug development by ensuring the patient voice is captured. Patient input also helps to ensure the questionnaires or diaries used to collect this information in a trial are appropriate and are measuring the outcomes in the right way. As a result, the treatment benefit information can be included in labeling in a way that is accurate and not misleading.

What is a clinical outcome assessment and how are COAs captured in drug development?

COAs are simply the patient-focused tools that we use as part of our assessments of clinical outcomes such as how patients feel or function in their daily lives. These measurements of patient outcomes provide essential information about benefits and risks of a drug. COAs are captured using four types of COA measures: patient-reported, clinician-reported, observer-reported, and performance outcome measures. The type of COA that is used depends on the particular research question and the context in which it will be used.

COAs can be used to support product approval and claims of treatment benefit in drug labeling. Just as with any other tool, a COA measure must be fit for its intended purpose in drug development. FDA regulations state that assessments used to support labeling claims of treatment benefit must be well-defined and reliable; this is so that changes seen in the outcome assessment can be interpreted and described as a clear treatment benefit.

What are patient-reported outcomes?

Patient-reported outcomes (PROs) are outcomes that are based on reports coming directly from the patient about how he or she feels or functions as a result of treatment. The patient’s report is documented without changes or interpretation by a health care professional or anyone else. A PRO can be a self-report using a journal or answering written questions in a questionnaire, or it can be administered by an interview. An example of a PRO is a patient’s self-report of pain intensity over the past 24 hours on a numeric pain rating scale of 0 (no pain) to 10 (worst pain imaginable). 

Symptoms known only by the patient, like pain severity, can only be measured by patient reports. Over the last few years there has been increasing interest among patients, drug developers, health care professionals, insurance payers, and regulators in the development and application of PRO instruments in drug development, particularly to support product labeling claims. Importantly, PROs may not always be feasible or appropriate depending on the particular context, and other types of COAs may be utilized.

What is the COA Compendium? And what is its purpose?

The COA Compendium is a table that describes how COAs have been used in drug development to measure the patient’s experience (such as disease-related symptoms) and support labeling claims. It also identifies COAs that have been qualified for potential use in multiple drug development programs and recognizes ongoing COA qualification projects to encourage community collaboration in the development of COAs for unmet measurement needs under CDER’s Drug Development Tools COA Qualification Program.

Basically, the COA Compendium is a communication tool that we intend to ultimately serve as a living document updated on a regular basis. By including COAs that have been used successfully in previous drug development programs, the COA Compendium is intended to facilitate communication and to provide clarity and transparency to drug developers and the research community. It will collate and summarize information for many different diseases and conditions into a single resource.

The compendium is designed to be used as a starting point when considering the use of COAs in clinical trials and to promote early engagement and discussions with the FDA around selection of COAs that are most appropriate for a drug development program. We envision it will be most helpful in the very early phases of drug development when drug developers are planning future trials. We also aim to facilitate discussion about how COAs can be used in clinical trials and spur innovation and development of COAs in needed therapeutic areas.

Why is this COA Compendium important and what does it mean for patients?

Capturing outcomes that are important to patients is a high priority for CDER. As I mentioned earlier, the COA Compendium is another tool to foster our patient-focused drug development mission. We hope this tool will make it easier to see the knowledge gaps and where attention is needed to develop patient-focused outcome assessments. 

Before a product can be developed to treat a disease or condition, we have to know how the disease or condition is affecting the patient. After gathering this information from patients, we can define the specific aspects of a disease or condition that we aim to treat and select appropriate outcome measures. 

We hope that collating and listing outcome measures for many diseases and conditions in the COA Compendium will encourage the use and development of patient-focused outcomes in future clinical trials. We plan to continue our engagement with the public and the scientific community to support pertinent future program and policy development activities.

Is FDA encouraging drug companies to consider using PROs in trials that support approval of a drug?

Yes, we want to encourage development and use of clinical trial endpoints that provide information that is meaningful to patients who are considering taking a drug. These often include PROs, but may also include other COAs, overall survival, or biomarkers, depending on the particular circumstances in which they will be used. We encourage drug developers to consider incorporating adequate, well-defined, and reliable outcome measures and to discuss those measures with us as early as possible in product development.

Will this compendium be an all-conclusive list of COAs?

No, a comprehensive table of all COAs is not our goal with this project. The list will not be exhaustive. It is also not meant as a replacement for existing communication channels with CDER review divisions. Nor is it a replacement for existing, disease-specific guidance or qualification efforts. The pilot COA Compendium includes a small proportion of COAs from new drug labeling, which we hope to get public comment on before efforts are made to expand its scope. 

Where can people find the COA Compendium?

We have issued a Federal Register notice seeking review and comment on the content and format of the compendium. The compendium can be also be accessed through the FDA’s website where  a new dedicated webpage provides information about COAs and a guide to using the document. 

What type of information are you hoping to obtain?

We are seeking public feedback on the utility of the COA Compendium, the approach for development of the COA Compendium, and any suggestions for future approaches to expand its scope. We want to hear from patients,industry, health care professionals, payers and other the stakeholders that have an interest in the development and use of COAs in drug development.

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