FDA’s New Guidance on Patient-Reported Outcomes

We’re big fans of patient-reported outcomes (PROs) here at PatientsLikeMe, defined by the Food & Drug Administration (FDA) as:

“A measurement based on a report that comes directly from the patient about the status of a patient’s health condition without amendment or interpretation of the patient’s response by a clinician or anyone else.”

qolThe self-report questionnaires we use on PatientsLikeMe to measure your health (such as the mood map, ALS-Functional Rating Scale/ALS-FRS, and other rating scales) are all examples of PROs, and they’re designed to accurately reflect the level of disease severity for a particular condition. Contrast PROs with the results of a blood test or an MRI scan; these are measured by someone other than the patient and are interpreted by healthcare providers. When a disease is relatively well understood and can be measured directly, as in HIV, measurement can be performed with objective measures such as blood levels (e.g., CD4 count and viral load). However, for many disease there is no objective measure for a disease (e.g., fibromyalgia). That means that trials and other clinical research studies are dependent entirely on the report of the patient themselves through PRO instruments. The FDA has recently released a new report: “Guidance for Industry: PRO Measures: Use in Medical Product Development to Support Label Claims.” This report provides guidance on the design of new instruments, and evaluation of old instruments, to let scale designers know how to get their PRO taken seriously by the FDA, with a view to making claims on the prescribing label. This report has many positive aspects which we believe will improve the quality of PROs in research. For example:

“Sponsors should provide documented evidence of patient input during instrument development and of the instrument’s performance in the specific application in which it used (i.e., population, condition).”

  • We’ve always believed strongly that PROs should come directly from the patient’s experience, and we already consult extensively with patients (as well as clinicians and researchers) in the design of each new community. We’ve also done novel research this way, collaborating directly with a group of previously unmeasured ALS patients to ensure their PRO scale was able to reflect their experience with advanced forms of their disease.

“Characteristics of the PRO instruments that are reviewed by the FDA include the following: Number of items… data collection method… administration mode… response options… recall period… respondent burden… translational / cultural adaptation availability.”

  • These are all important factors in PRO development that are frequently overlooked. For instance, a survey that takes too long to complete will tire patients out and could adversely affect the quality of the data. A survey that depends on a patient being highly literate or wealthy could bias findings and make the tool unusable in the developing world. When patients complete our PROs on the site, there is no healthcare provider nearby they can consult for clarification; we work hard to ensure our questions can be easily understood and are unambiguous.

“We encourage instrument developers to make their instruments and related development history available and accessible publicly.”

  • Although only “encouraged” and not mandated, this is a step in the right direction. Too often new scales are developed (or old ones modified) without clear justification or transparency. Here at PatientsLikeMe we are planning to embark on our own efforts to validate our existing scales, some of which are widely-used gold standards, others of which we developed in-house. Where possible, we’ll publish our methodology to the scientific community so that others can benefit from what we’ve developed.

“Because statistical significance can sometimes be achieved for small changes in PRO measures that may not be clinically meaningful (i.e., do not indicate treatment benefit), we encourage sponsors to avoid proposing labeling claims based on statistical significance alone.”

  • This is an important point. If we created a pain scale which went from 0-100 (0=no pain, 100=unbearable pain) and gave it to enough patients in two groups (say, a thousand in each group), then it’s quite likely we could come up with a small but statistically meaningful difference. However, just because it’s statistically significant, is it really worth the cost, the risk of side effects, and the treatment burden to go from 80/100 to 78/100? This part of the guidance reinforces this notion and will encourage investigators to fine-tune their instruments for responsiveness. We’re already examining our existing scales to establish what we call “minimally important differences” (i.e., how much of a change on the scale is really a meaningful change as opposed to random variation in the measure?).

The report also contains (as an appendix) a sort of “how-to” recipe for submitting evidence in support of a PRO. We are fully support this guidance and look forward to the day when PROs developed from data on PatientsLikeMe can be used to support label claims for clinical research.

PatientsLikeMe member PaulWicks PatientsLikeMe member Mike Massagli

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