Effectiveness Research Can Help Sponsors Address
‘Real-world’ Benefits and Secure Reimbursement

Although the U.S. Food and Drug Administration (FDA) and other regulatory agencies around the world require that medical product sponsors provide evidence of a drug’s or a medical device’s efficacy in order to gain market entry, they do not, in most cases, require that data on a potential product’s effectiveness be produced.

However, as federal legislation calls for increased comparative effectiveness data and as both commercial and government payers demand additional documentation of what a product’s benefits are when it is used outside of a strict clinical research setting, sponsors may need to provide data on the effectiveness of their products in real-world settings after they have been marketed.

“Put simply, efficacy is a measure of how well a drug or vaccine or medical device works in clinical trials, such as those conducted to gain market approval, and effectiveness is a measure of how well that product works in clinical practice when applied to a broader range of patients,” said John Seeger, PharmD, DrPH, Vice President of Epidemiology at i3 Drug Safety.

“The differences between the two are related to several factors. For example, in clinical trials to establish efficacy, the patients taking a drug are screened in accordance with the inclusion/exclusion criteria in the protocol, but in practice, once that drug is on the market, clinicians use their best judgment about the risk/benefit of the product for the patient, who may have other conditions and may be taking concomitant medications,” according to Seeger.

Other factors that have an impact on effectiveness can include patient adherence to the therapy and the duration of the study. During clinical trials, adherence is typically more closely monitored and the duration of therapy tends to be short, he explained. “If safety or efficacy as observed in clinical trials is not maintained in the real world, then the benefit/risk assessments based on the clinical trial data may lead to incorrect treatment decisions. Further, revised safety and effectiveness data could lead to a change in how the product is used, leading either to a larger possible target patient population or to a smaller one, defined on the basis of this risk/benefit assessment,” he said.

ARRA’s call for effectiveness research

The American Recovery and Reinvestment Act of 2009 (ARRA) designated $1.1 billion for comparative effectiveness research (CER), which, according to the Department of Health & Human Services (HHS), “is essential for clinicians and patients to decide on the best treatment. It also enables our nation to improve the health of communities and the performance of the health system.”¹

CER compares the relative effectiveness, safety, cost and other clinical and economic outcomes of two or more health care interventions used to prevent, diagnose or treat diseases, disorders and other health conditions under real-world conditions. In other words, sponsors may have sound efficacy data from randomized, controlled clinical trials – which take place under ideal conditions against a placebo and can prove that a treatment works versus doing nothing – but to inform market use judgment calls and coverage decisions, they also may need rigorous evidence of effectiveness in realistic conditions.

“Although there hasn’t been a requirement to determine effectiveness in the past,” Seeger explained, “the ARRA CER provisions now provide for it. Even without this mandate, however, there is value to doing effectiveness studies, especially where there appear to be differences between efficacy and effectiveness.” He noted that even where there are not differences, sponsor companies might wish to develop sound data demonstrating effectiveness because “health plans and countries or agencies that pay for care may want that information before agreeing to reimburse the product.”

Also, if the question of effectiveness is raised about a product during the approval process or after the product is on the market, clinicians may shy away from its use or payers may be reluctant to reimburse it. “If sponsors don’t have the data to show that their product is effective in actual practice, a cloud may be cast over the product,” Seeger said. “As a result, reimbursement strategies may fail, with potential loss of market.”

Measuring effectiveness requires data, expertise

Some metrics from a product’s clinical development, such as changes in blood pressure or cholesterol measures can be directly applied in an effectiveness setting. “Determining a measure that makes sense is pretty straightforward,” he indicated. “The biggest challenge is access to data, because primary data collection is both time-consuming and expensive.”

Gaining access to comprehensive data and to the sophisticated technology and epidemiological tools they may need to conduct effectiveness research can be much easier when sponsors join forces with i3 Drug Safety. Epidemiology researchers within i3 Drug Safety have expertise in using observational data derived from its Normative Health Information (NHI) database to answer real-world effectiveness and safety questions with relative ease, Seeger explained.

“Using health care claims from the large and comprehensive NHI database allows i3 epidemiologists to translate claims to usable solutions and a greater understanding of how population health can be measured and quantified,” he stated. “Our technology brings it all together because we have the computing resources that permit the query and processing of such a large amount of data, which is not a trivial task.”

Effectiveness case study: RotaTeq®

These capabilities were utilized by Merck when its rotavirus vaccine, RotaTeq, came to market with a postmarketing commitment regarding safety monitoring. Prior to the approval of RotaTeq in 2006, Wyeth Lederle Vaccines’s RotaShieldÒ in 1998 had been the first vaccine approved to prevent rotavirus gastroenteritis in the United States.

However, RotaShield was taken off the market in 1999 because it became associated with a rare, but potentially life-threatening side effect: intussusception (a type of bowel obstruction that occurs when the bowel folds in on itself).² This is an example of what can happen when a larger population in a less-controlled setting takes a drug or vaccine that meets efficacy requirements during clinical trials: They may experience different benefits or side effects than those seen during the clinical trials phase.

To help ensure that RotaTeq was effective and did not pose the risks that RotaShield did, Merck worked with i3 Drug Safety epidemiologists to monitor cohorts of infants that either received the vaccine or did not, using the i3’s comprehensive health insurance claims database. An effectiveness study based on these cohorts found that the RotaTeq vaccine was more than 95 percent effective in preventing rotavirus gastroenteritis and in reducing health care resource utilization.³

This type of effectiveness data can be presented at scientific and medical conferences, and can be submitted to regulators and payers as warranted. “There is a lot to be said about the value of data on the effectiveness of a product rather than relying on efficacy found during clinical trials,” Seeger noted.

“i3 epidemiologists play an important role in measuring and quantifying population health,” he said. “i3 offers a unique combination of data resources, technology and expertise that can help our clients answer effectiveness and comparative effectiveness questions in a timely manner.”

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