The FDA has long recognized patient-reported data in clinical trials. Many widely used drugs have been approved primarily based on patient-reported improvements. Migraine drugs are typically approved using patient diaries measuring levels of pain relief, phonophobia, photophobia and nausea; the primary endpoint of depression trials is the change from baseline in a standard depression rating scale; Pfizer’s Lyrica (pregabalin) showed efficacy in neuropathic pain based on a difference in average self-reported pain scores between patients treated with Lyrica and placebo; and the list goes on. Whether FDA’s acceptance of these patient-reported endpoints is due to FDA’s belief in the value of patient-reported outcomes (PROs), or due to the lack of a ‘harder’ endpoint for these trials is debatable. However, below is a selected list of drugs primarily approved based on PROs, and their peak WW sales. One can see that relying on patient-reported clinical data has not hindered the success of these products.
FDA Guidance on Patient-Reported Outcome Data
In December 2009, FDA issued a guidance document instructing industry on how to use PROs in drug development and clinical trials. Although FDA has historically accepted patient-reported outcomes for approval when a more objective endpoint is lacking, they have been very reluctant to include secondary PRO endpoints (such as improvements in quality of life) in approved product labeling. Some in industry have viewed this new guidance as sign of a shift within FDA toward the importance of patient experience and quality of life measures. If true, this could have a broad impact on the way drugs are designed, developed and marketed.
To date, PRO data has been underutilized in clinical practice. However, if FDA begins to recognize PRO measures such as quality of life, pharma companies will begin to generate data on their drugs’ impact on these measures. Physicians will have additional data available when deciding which drug might be best for their patients and will begin to rely more heavily on PRO data.
Importance of PRO Measures
There are many reasons to value PRO measurements. Some treatment effects are only known to the patient, and the patient provides a unique perspective on treatment effectiveness that goes beyond traditional clinical measurements. European pricing authorities have long valued the impact of quality of life on drug evaluation, using the quality-adjusted life year (QALY) measurement of disease burden, which includes both the quality and the quantity of life lived. But even for those who do not believe a focus on the patient is reason enough, there is evidence of the clinical importance of PRO measures. A study of 293 heart failure patients showed that patient-reported functional status was a prognostic predictor of hospitalizations, quality of life and death; and a meta-analysis of oncology research from 1982-2008 showed a correlation between patient-reported quality of life and survival in cancer patients.
Opportunity for mHealth
All of this, of course, creates a tremendous opportunity for companies working to collect patient-reported data, and I have previously written about the value of longitudinal personal health data streams, or healthstreams, that include both physician/system-generated data (EMR), combined with more frequently added patient-generated data. Traditionally, patient-reported data has been captured disproportionaley via written diaries. However, since the most common measures for a PRO instrument are based on the Likert scale and Visual Analog Scale (VAS), it seems clear that any PRO data commonly captured via written patient diaries can be more easily and efficiently captured by electronic means, and work is being done to validate electronic capture methods.
In the future, we will see this type of PRO data regularly captured by patients via mobile devices and mobile apps, and this data will become a common tool for physicians in clinical practice. Some companies, such as Ringful Health and ReliefInsite (recently acquired by PatientsLikeMe), are already moving in this direction with mobile versions of asthma diaries and pain journals.
Patient-reported outcomes data is valuable and gaining importance in the practice of medicine. When you see your first pharmaceutical ad featuring claims of improvements to quality of life, you will know the era of patient-reported outcomes has arrived.