Quality-of-Life Data: Are the FDA and Managed Care Listening?

Quantifying QoL outcomes has been challenging historically—but now it’s more critical than ever.

By Olivia J. Banyon

Although quality of life (QoL) has been around as an assessment of health status for 20 years, standards for its measurement are still not universally accepted. Because QoL outcomes are based on subjective information, they’re considered less quantifiable than objective clinical data such as cholesterol or HbA1c levels. In addition, little consistency exists among policy holders such as the FDA and EMEA (European Medicines Agency), payers, scientists, and researchers in the way QoL is measured and interpreted. Without consistent standards, the value of QoL data will continue to be questioned. Pharmaceutical manufacturers can help shape the role of QoL data in the marketplace by understanding partnership opportunities and areas of efficiency in research.

The most widely used and validated QoL instrument in the world is the Medical Outcomes Short-Form 36-Item Health Survey (John E. Ware et al.), or SF-36(v2). The SF-36 evaluates the health-related quality of life (HR-QoL) of patients with different disease and health conditions and is considered a measure of health status as opposed to that of a specific age, disease, or treatment group. It has been translated for use in more than 50 countries as part of the International Quality of Life Assessment (IQOLA) Project. The SF-36 has been used to assess patient-reported health outcomes for more than 200 diseases and conditions. The SF-36 provides scores for physical and mental health in eight domains (see chart, left).

Many diseases and conditions have an impact in one or more of these domains. For example, patients’ quality of life with osteoarthritis or fibromyalgia is likely affected in the functional, physical, pain, and general domains. A different condition—such as a patient with an ileostomy in need of an ostomy appliance—may be affected in the functional and physical domains, too, but also in the areas of vitality, social functioning, and emotional and mental health. The HR-QoL impact of these conditions is central to a health economics value proposition. Therein lies an important application to managed care. Ideally, a pharmaceutical company’s health economics and outcomes research team works with the medical team during the early-phase clinical trial design to incorporate QoL and HR-QoL patient-reported outcomes (PROs) that will contribute to economic value during the commercialization phase. This requires that all teams have the foresight and understanding to translate the clinical manifestations of the disease into functional impact and be able to assign an economic value to the improvement or loss of function. Despite the historical challenges of QoL data, the marketplace is showing increased demand for health-related QoL data. A few of the primary forces driving this demand (see diagram, opposite, at bottom) are FDA and EMEA Guidance, evidence-based medicine (EBM), payer pressures, and new QoL assessments.

FDA and EMEA Guidance: Time for Clarification
The FDA has reevaluated regulations on advertising products’ QoL benefits. For any QoL claim to be allowed in pharmaceutical promotion, the FDA requires the same outcome claim be supported by a minimum of two adequate and well-controlled studies. The problem is the lack of consensus on what QoL is and how it should be measured. In 2006 the FDA issued a Guidance document suggesting a need for a more standardized, frequent, and structured approach to integration of PROs and QoL data. However, the Guidance itself created confusion around definitions of QoL and PRO. The EMEA issued a document that focused more on clearly differentiating HR-QoL from PROs and from the core symptoms of the disease. All PROs are not measures of health status, as the FDA Guidance suggested. QoL has traditionally been an umbrella term covering both health status and quality-of-life outcomes, which lends to the confusion in clinical trial design. A case can be made that the integration of PROs and QoL earlier in a brand’s lifecycle and phase of clinical trial development is the only way to truly assess particular treatment effects. PROs—which include QoL, measures of symptoms, health status, functional status, treatment adherence, and satisfaction with care/treatment—represent useful data to corroborate clinical trial data. While the 2006 Guidance has encouraged a standardized approach, the FDA still needs to address definitions, measurement, and distinction of QoL and HR-QoL. If the FDA is going to require the pharmaceutical investment to collect PROs, it will need to clearly delineate acceptable measures of QoL, HR-QoL, and health status.

Pharmaceutical manufacturers are often challenged to detect disease-specific differences with general QoL instruments such as the SF-36. Instead, manufacturers invest in developing disease-specific QoL assessments with the goal of detecting smaller, clinically significant changes. However, this can be an expensive and often fruitless endeavor if the FDA is unwilling to accept an unproven instrument. The FDA Guidance suggests that the use of standardized general assessments such as the SF-36 may increase the efficiency of FDA NDA submissions and provide the basis for easier clinical therapeutic decision making. One proven and reliable disease-specific QoL assessment is the Well-being Questionnaire (W-BQ12). The W-BQ12 is a generic measure of well-being developed by Clare Bradley of the University of London, UK. Many years were spent psychometrically validating the assessment in 37 languages for a range of populations including those with diabetes (type 1 and 2), macular disease, and growth hormone. Pharmaceutical researchers need to balance the more structured FDA Guidance approach with an assessment that corroborates clinical disease-specific data. A much wiser investment for pharmaceutical manufacturers, therefore, is determining and applying the clinical relevance of a more widespread assessment such as the SF-36.

While the FDA Guidance document was an important step toward standardization, it made no recommendations about the interpretation of PROs, QoL, and HR-QoL data on a therapy’s clinical significance or usefulness in therapeutic decision making. For this and other reasons, evidence-based decision making has recently returned to the spotlight among academic institutions, think tanks, associations, and payers.

Evidence-Based Medicine (EBM)
The impact of a medical or pharmaceutical intervention on a patient’s quality of life is central to the principles of evidence-based decision making. QoL measures such as the SF-36 contribute to medical decision making by providing insights into how treatments affect patients while offering both patients and physicians greater information on the risks and benefits of a treatment. EBM has its own lack of agreement in the industry, but suffice it to say that in the future, QoL, PROs, payer reimbursement, and FDA approvals will all be influenced by EBM applications.

Payer Pressures
Compounding the FDA’s more rigorous requirements on pharmaceutical manufacturers are increasing pressures from payers to evaluate the usefulness of any product seeking coverage. With the high degree of variability in measuring and interpreting PROs including QoL data, payers often resort to limited classifications of products based on indication or statistical results. This approach is limited due to differences in study design, including sample selection, size, and methodology, without consideration of clinical relevance, giving rise to reinvigorated discussion of EBM.

PROs can provide additional data for inclusion of a drug in a formulary, making that drug more competitive than others in its pharmacological class. Furthermore, an effective and well-tolerated drug with a demonstrated positive impact on patients’ health status and daily life may affect reimbursement decisions. Commercial and public payers have an even greater pressure to compete today based on their ability to control costs while delivering improved quality of care. PROs and outcomes research are critical to evaluating services offered by various plans (see diagram on previous page).

In general, payers/Managed Care Organizations (MCOs) are inconsistent in their application of QoL data. MCOs may require QoL outcomes for many reasons, some of which are opportunities for pharmaceutical collaboration. Aetna Health Plans has been evaluating the use of outcomes research in clinical decision making since the early ’90s. As an organizational case study, it is probably one of the most representative samples to consider. Aetna generally has a three-step process of applying outcomes research:

1. Technology Assessment: evaluation of the contribution of the innovation vs. the benefits of a new technology. Over 100 new technologies are evaluated each year, including the new technology’s impact on QoL and in making coverage policy decisions.

2. Clinical Guideline Incorporation: if the new technology is considered effective, clinical guidelines can be created to assist clinical staff.

3. Development of Internal Institutes of Excellence.

Aetna is one of many plans that consider health outcomes measures of function, disability, and patient satisfaction alongside basic measures of morbidity and mortality. However, for health outcomes measures to penetrate a payer environment, pharmaceutical manufacturers must consider the payer’s level of sophistication in evaluating health outcomes. This includes staff ability to understand the clinical relevance and significance of a health outcome. To advance their payer relationships, pharmaceutical companies must understand the payer’s valuation issues with health outcomes. These issues range from internal to global challenges.

The cost vs. benefit assessment has been an area of great debate over the past few years. It is often difficult for payers to decide to support a new treatment if the benefits are only marginal improvements over older benefits while the costs increase significantly. With this scenario, payers limit use of a new product through restrictions such as Prior Authorizations (PAs) or greater cost-sharing with the patient (paying higher deductibles or co-pays). Other methods payers employ include provider utilization management techniques such as incentives.

Despite the real-world limitations on the value of QoL data, payers use this type of data to compete in controlling the rate of cost increases while improving quality of care, or value. Pharmaceutical manufacturers have many opportunities to make QoL and PROs more valuable for payers. These include focused research resources on products that improve quality and efficiency of care the most, consideration of effectiveness and cost effectiveness in clinical trial design, assessment of function and disability outcomes, training and support of internal payer staff on interpreting QoL data, and development of systems to apply QoL assessment standards.

QoL data has been shown to predict morbidity, hospitalization, and mortality in certain patient subpopulations. Pharmaceutical marketers cannot develop claims for a product without understanding the true value of PROs including QoL endpoints in the marketplace—the clinical meaningfulness and relevance. We need to incorporate PROs and QoL measures earlier in a product’s lifecycle by evaluating its safety, efficacy, and tolerability profile (negatively or positively) on a patient’s quality of life in terms of functional and physical ability. From a marketing perspective later in the lifecycle, these measures directly affect both short- and long-term compliance and ultimately the product’s effectiveness and uptake in the marketplace.

Olivia J. Banyon is Managing Partner of The Hobart Group suite of companies. Her background includes a unique blend of outcomes marketing responsibilities working at Pfizer, Acuity HealthGroup, and a Medco-Wyeth Joint Venture in disease management. Her graduate education is in Epidemiology/Public Health, and her undergraduate education is in Communications from the S.I. Newhouse School at Syracuse University. She can be reached at obanyon@thehobartgroup.com.v.com.