Drug Therapies: Measuring Quality of Life, Lotronex Dilemma

by Food and Drug Administration (FDA)

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Measuring Quality of Life

The World Health Organization defined "quality of life" in its constitution in 1948 to include physical, mental, and social well-being, and not just the absence of disease or illness. Although its definition raised considerable question as to whether or not quality of life could be measured, the comprehensiveness of the definition has set a standard by which many measurement efforts have been judged. Increasingly, however, experts have come to realize that the measurement of the quality of life is subjective, and the final determination will always be made by the patient.

Sometimes, the quality of a person's life can be improved with interventions that have little therapeutic benefit, but great impact on perception. After receiving acute medical care for his heart attack, 51-year-old Phillip Terry from Dallas became tentative about his life. But then, advised by his doctor to start a new cholesterol-lowering diet, Terry's own perception about the quality of his life began to improve.

To help assess the patient's own perception about quality of life, pharmaceutical companies have begun to use disease-specific questionnaires that try to determine what qualities are important to patients and those that have been improved by the treatment.

The Pediatric Asthma Quality of Life Questionnaire, for example, was designed to gather information about how the disorder interferes with the daily activities of children between 7 and 17. Once a baseline for interference is established, doctors can measure whether a drug or treatment lessens the interference or somehow restores what the child or the parent considers to be a better quality of life.

But these studies are not always easy to conduct or interpret. "Quality of life can be influenced by many aspects of treatment, including side effects," says Laurie Burke, RPh, MPH, of DDMAC. And one of the biggest questions, she says, is "whether the outcomes measured even add to what is already known about a product's effects on symptoms and functional status." Although these questionnaires have been used extensively for several decades, the measures were initially developed to classify the degree of one's illness and not necessarily to evaluate changes in functional status.

Two adequate and well-controlled studies are generally required to support any clinical treatment outcome claim. That ensures that the evidence is strong enough to reach a conclusion and is not the result of chance or bias. "A claim must not mislead either the patient or the practitioner into believing that a benefit may be achieved that has not been adequately demonstrated," Burke says. Claims can be misleading unless they tell the whole story, both good and bad, and there must be fair balance of the supporting data — the benefits, as well as any limitations.

Current policy for quality-of-life claims, says Burke, is complex, case-specific, and dependent on the quality-of-life measurement, the disease, the intervention, and the population studied.

"We know that individuals weigh quality of life differently," adds Janet Woodcock, MD, director of CDER. "And we also believe that health claims are about more than just the symptoms of a disease."

Industry's Perspective

Pharmaceutical companies struggle in a highly competitive marketplace. Each is trying to differentiate its prescription drugs from others that treat the same disease. Aggressive campaigns that rely on quality-of-life claims to change prescribers' habits can help separate one drug from the pack, especially when marketed directly to the consumer. But these distinctions must be based on quality-of-life approaches that have been validated. If not, the increasing use of quality-of-life claims could mean misleading promotions, increased health-care costs, and inappropriate prescribing.

Kati Copley-Merriman, chairperson of the Health Outcomes Committee at the Pharmaceutical Research and Manufacturers of America (PhRMA), the trade organization that represents the country's research-based pharmaceutical and biotechnology companies, says quality-of-life claims are about more than making profit. "What drugs are doing for patients extends beyond the traditional measures of safety and efficacy," she says. "The forthcoming guidelines for quality-of-life claims currently under review will help to broaden the value statements manufacturers can make about products and will more accurately reflect the patient's own beliefs concerning the effects of a drug."

The Lotronex Dilemma

The recent controversy surrounding the withdrawal of Lotronex — a drug used to treat irritable bowel syndrome in women — is one such example of how a drug can have a profound impact on the quality of a patient's life. Lotronex was the long-awaited "magic bullet" for Bonnie Clayton, the IBS patient. She says it gave her back some semblance of a life. But, while it has helped her, it has been fatal to others. And that's not an effect FDA takes lightly, especially when the disease itself is not life-threatening.

"FDA approved Lotronex because its benefits outweighed its risks for the population of intended patients," says Woodcock. But clinical trials only test new drugs in several thousand patients; when a drug goes on the market, it may be used by millions of people and then rare but serious side effects can show up. Another reason some risks, like the severe constipation and even deaths associated with Lotronex, don't show themselves during clinical studies, she adds, has to do with how drugs are used in the real world. In clinical trials, patients are carefully monitored. After a drug is out on the market, all kinds of different patients will be treated with the drug. Some won't even have the condition for which the drug was approved — unlike Bonnie, who has known for more years than she cares to remember that she suffers with IBS.

"I am literally in tears," she says. "My life, which had just begun to achieve some normalcy again, will now revert back to the horror it once was."

While the withdrawal of Lotronex has been difficult for the patients it has helped — more than 2,000 Lotronex patients sent e-mails to CDER chief Woodcock complaining about the decision to remove the drug from the market — the case presents a clear example of how the safety and efficacy of a treatment can be inextricably linked to quality-of-life issues. From the agency's viewpoint, however, quality-of-life concerns cannot outweigh the safe use of a drug.

Woodcock reminds those who sent the e-mails that FDA tried to work with the manufacturer to find a way to keep the drug on the market safely. The agency had serious concerns about the severity and number of adverse reactions resulting from the use of Lotronex, but believed that a restricted drug distribution program would allow safe use of the drug in appropriately informed and closely monitored patients. Instead, the manufacturer chose to withdraw the drug.

On the Horizon

For now, several groups, including PhRMA, are working with FDA to consider the agency's regulatory approach to quality-of-life claims. This initiative is part of an ongoing effort with international counterparts to harmonize whatever regulations emerge, and to bring some order to the field. As this field of research develops and reliable standards for marketing claims are put in place, clinicians can start to understand which type of medical or clinical intervention offers a better quality of life for patients.

The challenge FDA faces in defining and measuring quality of life, and in regulating quality-of-life claims made about drug therapies, comes back to the very personal perceptions of patients and what they value as they grapple with life-altering diseases and equally life-altering therapies. Heart patient Phillip Terry is an example of how important these intangible influences can be to a patient's perceived quality of life: Although most of the dietary changes he has made will likely have little impact on his medical condition, they give him a sense of control. And that, he says, can make all the difference. "Sometimes a person just needs to gain his confidence back."

About the Author

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FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.