The importance of patient-reported outcomes … it's all about the patients

FDA Consumer, Nov-Dec, 2006 by Linda Bren

A visit to the doctor often means being poked and prodded with various instruments, such as a thermometer stuck in the mouth, a stethoscope placed on the chest, or a blood pressure cuff wrapped around an arm

All of these instruments give the physician measurements--blood pressure, temperature, heart rate--that help in diagnosing or treating an illness.

But none of these instruments measure how much pain patients feel, how depressed they are, how well they sleep at night, or whether they have enough energy to walk up a flight of stairs. That information must come directly from the patients.

Along with getting a physical examination and lab tests, patients are routinely asked how they are feeling or how well they are functioning, says Robert Temple, M.D., director of the Food and Drug Administration's Office of Medical Policy, but the information they provide is filtered through a "knowledgeable interpreter"--the physician.

For example, a person with heart failure will be examined for large amounts of fluid in the body tissues (edema), for fluid in the lungs, and for abnormal heart sounds. He or she might get a chest X-ray or echocardiogram, and would be asked about his or her ability to exercise. The patient would be given a heart failure classification, a widely recognized four-category description of the severity of exercise limitations that makes use of nonstandarized questions and has considerable room for judgment.

A person with asthma would undergo a similar evaluation, including an assessment of how limiting the asthma had been. In all of these evaluations, the patients' own assessment of their well-being has not been ignored, but their reports have been interpreted by the physician.

"Physicians ask the patient questions and come to a conclusion," says Temple. "There's nothing inherently wrong with that, but it's unstructured and very operator-dependent."

Increasingly, however, information about symptoms and performance is being obtained directly from patients using structured questionnaires that are shown to give reproducible, meaningful, quantitative assessments of how patients feel and how they function-measures that are called patient-reported outcomes, or PROs. The questionnaires used to collect this information are called PRO instruments.

What is really new, says Temple, is that these instruments are being used to assess symptoms without the physician's interpretation. "The use of PRO instruments is part of a general movement toward the idea that the patient, properly queried, is the best source of information about how he or she feels," says Temple.

The FDA is encouraging the medical research community to use PROs in clinical trials to help tell whether a new drug or medical device is working and how well it is working. If PROs are collected, measured, and assessed properly, the information can be used by drug or device developers to support the approval of a new medical product and claims about that product.

Beyond clinical trials, researchers also are investigating how PROs can be used in clinical practice to enhance the treatment of patients.

The goal of using PRO measures is to provide better information to doctors and patients so that the best treatment for patients can be determined, says Laurie Burke, R.Ph., M.P.H., director of the FDA's study endpoints and label development team in the Office of New Drugs. "It's all about the patients."

Ensuring Reliable PRO Instruments

"Just like a doctor may ask, 'how are you feeling today,' but then probes with further questions, a PRO instrument probes in a structured, formal way," Burke says.

Getting information directly from patients about their symptoms and about how they feel or function is not new. "Patients are the only source of information about their symptoms and this information has a critical role in drug assessment," says Burke, "even if structured instruments are not used." More recently, many researchers have developed their own PRO measuring instruments, she says. "But the problem is that although those measures are familiar to the people who developed them, we often can't interpret the measures."

The FDA is working with the research community, the pharmaceutical and medical device industry, and other government agencies to ensure that the PRO instruments used are reliable, interpretable, and valid--in other words, that they measure what they are intended to measure and that they are backed up by solid, scientific rationale.

Why Use PROs?

PRO instruments offer a structured interview technique that minimizes measurement error and ensures consistency, ultimately providing a more reliable measurement than one that can be obtained by informal interviews.

PROs are useful because some treatment effects are known only to the patient, says Bob Rappaport, M.D., director of the FDA's Division of Anesthesia, Analgesia, and Rheumatology Products, and it is helpful to standardize the questions asked of patients. For example, pain intensity and pain relief have always been measured with PRO instruments. "In most cases, the only way to know if someone is feeling better is to ask how much pain they are in," he says.