Who Cares About What Patients Think? The FDA, Insurance Payers, Researchers… Maybe You Should Too

While patient-reported outcomes (PROs) are nothing new in the field of medicine, they may now be newly appreciated.

The U.S. Food and Drug Administration (FDA) defines a PRO as “a measurement based on a report that comes from the patient (i.e., study subject) about the status of a patient’s health condition without amendment or interpretation of the patient’s report by a clinician or anyone else.” In other words, a PRO is how the patient feels, and how well or poorly a patient is responding to treatment, according to the patient.

However, according to Amy P. Abernethy, MD, PhD, a medical oncologist and palliative medicine specialist at Duke University Health System, that type of information, which she more broadly referred to as “patient-generated health data,” has been reported by patients at the beginning of every doctor’s visit for centuries.

“For doctors, patient-reported data are the beginning of every story; it is the history of the patient’s present illness,” Dr. Abernethy told ASH Clinical News. “When you go back to good old-fashion doctoring, we have always collected information on symptoms, quality of life, and personal concerns – so-called patient-reported outcomes – but recently we have gotten better at it and have been able to systematize it and make it a priority.”

As medical research has advanced during the last several decades, important research endpoints and goals have revolved around survival, disease biomarkers, progression, prevention, or genetic risk. The new millennium has widened that focus to include PROs such as physical functioning, self-image, psychological status, quality of life, and more.

ASH Clinical News recently spoke with several physicians actively studying PROs and working to expand their use in medicine and asked them to comment on the growing importance of PROs and how their measurement is changing the health-care landscape.

Why the Sudden Interest?

Although formalized PRO measurements have been around for decades, Dr. Abernethy acknowledged that they have gained more attention in recent years, and the reasons for that are many-fold.

The increasing importance of PROs may be related to increasing success in treating cancers such as hematologic malignancies, according to Gregory A. Abel, MD, MPH, hematologic oncologist and health outcomes researcher at Harvard Medical School.

“Patients with blood cancers are living longer these days,” Dr. Abel said. “A good example is chronic myeloid leukemia: we used to think mostly about how to get patients with CML to live longer, but as survival has improved, we are worrying more about the quality of patients’ lives, as well.”

Clinical advances in the field have paralleled technologic advances. For many years, there were not data systems available to easily collect patient-reported data, Dr. Abernethy added.

“The rise of technology made collecting, storing, analyzing, and monitoring this information easier and more doable; before, any survey done just got lost in a patient’s chart,” she said.

The patient-centeredness movement started to gain real momentum about five to seven years ago, said Ethan Basch, MD, MSc, director of cancer outcomes research program and associate professor of medicine and public health at the University of North Carolina at Chapel Hill. One of the most influential parts of that movement was the 2009 release of the FDA’s Guidance for Industry document discussing PRO measures, which detailed how the FDA would evaluate PRO instruments that drug and device manufacturers use to support claims on medical product labels.¹

“The FDA document raised PROs in the consciousness of researchers and, simultaneously, there was a rise in interest bringing the patient perspective into comparative-effectiveness research,” Dr. Basch said.

Comparative-effectiveness research started to gain legs around the time of the American Reinvestment & Recovery Act, which provided $1.1 billion for major expansion of comparative-effectiveness research. In addition, with the passing of the Patient Protection and Affordable Care Act in 2010 there were multiple provisions around patient-centeredness, including the creation of the Patient-Centered Outcomes Research Institute (PCORI), which was given a “mandate to improve the quality and relevance of evidence available to help patients, caregivers, clinicians, employers, insurers, and policy makers make informed health decisions.”²

“The creation of PCORI made waves in the research world,” Dr. Basch said. “Following the lead of PCORI, multiple major funding agencies are starting to include some degree of patient-centeredness or patient engagement within funding requirements. This has become a central concept in clinical research design.”

Who’s Concerned with PROs?

How a patient feels, and how well that patient is doing, is essential information for his or her treating physician. Because of that, many more players in the health care community are paying attention to PROs, including the FDA and insurance payers.

“A huge proportion of the treatment that we administer or the services that we provide are aimed at improving how patients feel and function,” Dr. Basch said. “In addition, many treatments and services can negatively impact how a patient feels and functions; and if we do not measure that we cannot truly understand how people are doing.”

In addition to releasing its industry guidance document on PROs, the FDA had participated in the formation of a Patient Reported Outcomes Consortium aimed at developing, evaluating, and qualifying PRO instruments with the FDA for use in clinical trials. The agency has also committed to a new initiative called Patient-Focused Drug Development as part of the Prescription Drug User Fee Act (PDUFA) V. Over the 5-year period of PDUFA V the FDA will hold at least 20 public meetings each focused on a specific disease area. These meetings will attempt to more systematically gather patients’ perspectives on their conditions and available therapies to treat their conditions.

“The FDA is taking this area very seriously, not only by holding focus groups but by increasing internal personal with expertise in PROs,” Dr. Basch said. “Ideally, the FDA would like to see PROs used more frequently in a rigorous way and be part of application packages and included in labels.”

One of the most relevant examples of the FDA incorporating PROs into its decision-making process is that of ruxolitinib, an oral JAK1 and JAK2 inhibitor. The FDA approved ruxolitinib for the treatment of intermediate-and high-risk myelofibrosis in November 2011, and subsequently for polycythemia vera in 2014. The drug was approved based on two clinical trials, COMFORT-I³ and COMFORT-II,4 with primary endpoints of reduction in spleen volume. COMFORT-I also included a secondary endpoint based on a PRO instrument that researchers developed in conjunction with the FDA.

“The drug would not have been approved if it did not make people feel better; the reduction in spleen volume on its own was not a meaningful outcome,” Dr. Basch said.

According to Dr. Abernethy, it was key that the FDA understood how the PRO measurement was developed and could trust in the implications of a measurable change on the scale. “In addition, the measurement tool made sense in terms of symptom profile in that it went along with what patients expected to be feeling and experiencing in terms of developing spleen problems and other issues associated with that disease,” Dr. Abernethy added.

Payers are also taking a greater interest in PROs. For example, in the cardiology realm, when discussing treatments for heart failure, the metric of hospital readmission is often used to measure a successful treatment. However, patient symptoms such as shortness of breath, chest pain, sleep quality, and physical functioning are also important elements of heart failure treatment.

“People who have symptoms and functional status problems are more likely to use a lot more services,” Dr. Basch said.

In addition, medical associations are starting to use PROs in clinical practice guidelines as a way to prioritize one product compared with another in terms of clinical benefit and potential harms or side effects. “Some of the very large payer organizations are starting to prioritize treatment based on these guidelines and the quality-of-life information,” Dr. Basch added.

Incorporating How Patients Feel into Research

As PROs gain attention, many in the research world have begun to develop PRO measurement tools or incorporate them into therapeutic trials.

“There has been development and use of PRO tools for many decades, but more recently there has been consolidation in this space as urged by the National Institutes of Health and its PROMIS program,” Dr. Abernethy said. PROMIS is the Patient Reported Outcome Measurement Information System and it funded investigators to develop a “psychometrically validated, dynamic system to measure PROs efficiently in study participants with a wide range of chronic diseases and demographic characteristics.”

Currently, PROMIS tools measure physical health, mental health, and social health for adults and children. However, there is a large and wide portfolio of other instruments available to researchers interested in measuring PROs, Dr. Abernethy said.

In its guidance document, the FDA outlined some of the attributes that define a quality PRO measurement tool including content reliability, ability to detect change, and validity.

Reliability is a key factor. When administered to different people it is important that the tool can reliably get the same type of estimate for people with similar problems, Dr. Abernethy said. It is also important that the questions are understandable, meaning that people from different backgrounds can understand the questions and provide similar answers.

Responsiveness to change must also be evident in a quality PRO measurement tool. For example, if the use of a certain drug makes a difference to a patient’s life, it is important that the employed tool shows an evident change.

Validity – that an instrument measures what it is supposed to be measuring, when compared to a gold standard – is at the crux of any useful tool. “My first advice to anybody looking to develop a PRO measurement is to try to use something that is already out there and has already been validated, provided it fits your goal,” Dr. Abernethy said.

How to Use PROs in Clinic

According to Dr. Abernethy, physicians can use routinely collected PROs as a way of monitoring treatments and signaling what interventions a patient may need. Symptom-focused PROs are particularly helpful. “For example, when you see a patient in the clinic, you can systematically measure pain, which is a PRO,” she said. “If a patient comes in with hip pain and you ask them to rank the pain on a scale from zero to 10 and then apply a steroid injection, on their next visit you can revisit that pain and any shift in score could indicate that the intervention is working, not working well enough, or not working at all.”

Second, PROs can be used as a way to triage patients, when applicable. A patient presenting with chest pain and shortness of breath may need to go to the emergency department, or someone in psychological distress may need the aid of a social worker or a psychiatrist.

Depending on how, and if, each practice collects and stores PRO data, it can be used for a series of secondary purposes as well, Dr. Abernethy said. The question of how physicians can use PROs in their everyday clinical practice is one that Dr. Abel thinks is deserving of greater research.

“I worry that in our busy hematology practices we do not have a lot of time to tease out what a patient’s quality of life truly is,” Dr. Abel said.

For example, for patients with myelodysplastic syndromes (MDS), fatigue is a big issue. “Some patients with MDS think that being tired is just part of getting old, and miss out on treatments that could help because their providers don’t always probe the extent of their fatigue,” he said. “Measuring all patients’ quality of life in a rigorous way would take out some of the guesswork.”

Dr. Abel said there is a great need to continue to develop methods to measure and administer PROs, especially in certain specific disease states. One method that may be helpful is the use of electronic medical records with patient portals, which can allow physicians to email patients prior to an appointment to assess PROs and compare that information to PROs at prior visits or to other patients with the same disease.

Although PRO research is still a relatively young field, a recent systematic review published by Kotronoulas et al. in The Journal of Clinical Oncology showed that the use of PRO measures in cancer care was associated with increased supportive care measures, improved symptom control, and improved patient satisfaction.5

“For a long time PRO information was dismissed as subjective and less important than objective measures like survival,” Dr. Abernethy said. “As we have gotten smarter about ways to collect this information, scientists, the FDA, the research community, and payers have all begun to prioritize it.”—By Leah Lawrence


References

  1. U.S. Department of Health and Human Services. Guidance for Industry. Patient-reported outcome measures: use in medical product development to support labeling claims. December 2009. Accessed from http://www.fda.gov/downloads/Drugs/Guidances/UCM193282.pdf.
  2. Patient-Centered Outcomes Research Institute. “About Us.” Accessed from http://www.pcori.org/about-us.
  3. Verstovsek S, Kantarjian H, Mesa RA, et al. Safety and efficacy of INCB018424, a JAK1 and JAK 2 inhibitor, in myelofibrosis. N Engl J Med. 2010:363:1117-1127.
  4. Harrison C, Kiladijian JJ, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012;366:787-798.
  5. Kotronoulas G, Kearney N, Maguire R, et al. What is the value of the routine use of patient-reported outcome measures toward improvement of patient outcomes, processes of care, and health service outcomes in cancer care? A systematic review of controlled trials. J Clin Oncol. 2041;doi:10.1200/JCO.2013.53.5948

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