Regulatory Focus™ > News Articles > Researchers: Patient Reported Outcomes for Heart Failure Fail to Meet FDA Criteria

Researchers: Patient Reported Outcomes for Heart Failure Fail to Meet FDA Criteria

Posted 12 July 2016 | By Michael Mezher 

Researchers: Patient Reported Outcomes for Heart Failure Fail to Meet FDA Criteria

A team of researchers say that no currently available patient-reported outcomes for heart failure meet the US Food and Drug Administration's (FDA) criteria for supporting product approval.

In a recently published review in the Journal of the American College of Cardiologists, the researchers checked the patient-reported outcomes against nine criteria adapted from the 14 listed in FDA's 2009 guidance, Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims.

FDA defines patient reported outcomes as measurements "based on a report that comes directly from the patient (i.e., study subject) about the status of a patient's health condition without amendment or interpretation of the patient's response by a clinician or anyone else."

In its guidance, FDA says that sponsors should develop patient-reported outcomes with a clinical trial endpoint in mind, "so that the instrument development and performance can be reviewed in the context of the intended role, and appropriate statistical methods can be planned and applied.

FDA has placed a greater emphasis on patient preferences and engagement in recent years. Some of FDA's patient-centric measures include the creation of a new Patient Engagement Advisory Committee and issuing guidance on patient-reported outcomes.

In November, FDA Commissioner Robert Califf and other agency officials highlighted some of these efforts in a JAMA viewpoint, saying, "FDA is committed to integrating patient perspectives into its regulatory evaluations and decision making and also encourages medical product innovators and clinical researchers to collect information on patient perspectives to inform development programs."

Patient Reported Outcomes in Heart Failure

For heart failure specifically, the researchers say that patient-reported outcomes are useful in three scenarios:

  1. In clinical research, to evaluate treatment benefit
  2. For regulatory approval, to support a product label claim
  3. In clinical practice, to monitor disease progression and assist in treatment decisions

However, the researchers say that while partially validated patient-reported outcomes have a place in clinical research and practice settings, such outcomes require "rigorous" validation in order to be used for regulatory approval.

Based on FDA's guidance, the researchers narrowed down the criteria for patient-reported outcome acceptability for regulatory approval to nine items: documented content validity, development for heart failure, preferred administration route, recommended recall period, demonstrated reproducibility, proven internal consistency, demonstrated construct validity, proven ability to detect change and available responder definition.

According to the researchers' analysis, none of the 19 patient-reported outcome instruments met more than seven of the nine criteria, and on average the instruments met just shy of five of the criteria (4.84).

Patient-Reported Outcome InstrumentFDA Criteria Met
Cardiac Health Profile (CHP)5
Cardiac Self-Efficacy Questionnaire (CSEQ)4
Chronic Health Failure Assessment Tool (CHAT)4
Chronic Heart Failure Questionnaire (CHQ)5
Daily Activity Questionnaire in Heart Failure (DAQIHF)5
European Heart Failure Self-care Behavior Scale (EHFScBS)6
Heart Failure Needs Assessment Questionnaire (HFNAQ)3
Heart Failure Somatic Perception Scale (HFSPS)4
HeartQoL (HeartQoL)4
Kansas City Cardiomyopathy Questionnaire (KCCQ)7
Left Ventricular Dysfunction Questionnaire (LVD-36)6
MacNew Heart Disease HRQL Questionnaire (MacNew)5
Minnesota Living with Heart Failure Questionnaire (MLHFQ)7
Quality of Life Index – Cardiac Version (QLI)3
Quality of Life Questionnaire for Severe Heart Failure (QLQ-SHF)6
San Diego Heart Failure Questionnaire (SDHF)3
Seattle Angina Questionnaire (SAQ)5
Self-Care Heart Failure Index (SCHFI)6
Shortness of Breath in Heart Failure (SOB-HF)4

The most commonly failed criteria were documented content validity, recommended recall period and available responder definition, with only two of the 19 instruments meeting the researcher's definitions.

As such, the researchers say that none of the patient-reported outcomes they looked at would meet FDA's criteria to be used towards product approval. However, the researchers also say that FDA's criteria are more rigorous than other international regulators, such as the European Medicines Agency (EMA).

Between 2006 and 2010, the researchers say that EMA approved 47% of new products with data from patient-reported outcome endpoints, while FDA only approved 19%, all of which were also approved by EMA. During that time, only one heart failure medicine, Samsca (tolvaptan), was approved using a patient-related outcome as an endpoint in Europe. FDA also approved the drug, but relied on non-patient-reported outcomes data to make the approval.

Journal of the American College of Cardiology


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