Biased research, aggressive sales, harmful drugs

Approval from the U.S. Food and Drug Administration to market a new drug is a critical waypoint along the path to profits for pharmaceutical manufacturers. Unfortunately, recent case studies have illustrated that FDA approval does not necessarily provide assurances of effectiveness and safety. In this month's Georgetown University Health Policy seminar, we discussed two examples, anemia drugs and the diabetes drug rosiglitazone (Avandia), which were prominently featured in recent articles by Peter Whoriskey in The Washington Post.

Image courtesy of scienceblogs.com

The original impetus for the development of the anemia drugs Epogen, Procrit, and Aranesp, which mimic the  actions of the hormone erythropoietin, was to spare dialysis patients with severe anemia the inconvenience and risks associated with periodic blood transfusions. However, noted Whoriskey, pharmaceutical companies moved aggressively to market these drugs to a far larger patient population who were much less likely to benefit from them:

The trouble would arise as the drugmakers won FDA approval for vastly expanded uses, pushing it in larger doses, for milder anemia and for patients with a wider array of illnesses. Very quickly, the market included nearly all dialysis patients, not just the roughly 16 percent who required blood transfusions. The size of average doses would more than triple. And over the next five years, the FDA would approve it to treat anemia in patients with cancer and AIDS, as well as those getting hip and knee surgery.

Doctors were motivated to give more doses of these drugs due to generous financial incentives (estimated at between $100,000 and $300,000 annually for a typical oncologist) and the seductive thinking that if some drug was good, more was better. Even the publication of a 1998 study in the New England Journal of Medicine showing no survival advantage to boosting hematocrit levels to normal ranges in cardiac patients did little to discourage overprescribing. Not until 14 years later did an independent researcher obtain access to the complete study report from the FDA and conclude that the NEJM authors had used statistical slight-of-hand to obscure an increased risk of heart attacks and death in the normal-hematocrit group. In the meantime, lobbyists working for the drug manufacturers successfully blocked efforts by Medicare administrators to stop paying for the higher (harmful) doses.

Similarly, the evidence that rosiglitazone (Avandia) increased the risk of heart attacks was slow to come to light, due in part to the drugmaker's research emphasis on the surrogate outcome of glycemic control. Although a 2007 meta-analysis first sounded the alarm about rosiglitazone's cardiovascular risks, the manufacturer successfully stalled regulatory action in the U.S. for three more years, during which thousands of new patients were prescribed the drug.

Could the FDA and other U.S. government agencies do more to protect patients from the effects of biased research and aggressive sales tactics for newly marketed drugs? What concrete steps could health policymakers take to encourage research to identify unexpected harms earlier in the drug approval process?

- Kenny Lin, MD

  Director, Robert L. Phillips, Jr. Health Policy Fellowship

  Department of Family Medicine

  Georgetown University School of Medicine

Medicaid expansion is in the eye of the beholder

To supporters of the Affordable Care Act, legislative expansion of the Medicaid program is a welcome financial and health care bonanza for states and uninsured patients. To the ACA's detractors, Medicaid expansion is a hostile government takeover that must be opposed in principle, regardless of potential benefits of an infusion of federal dollars. The stage for these state-level clashes was set by a surprising Supreme Court decision last summer that upheld most major provisions of the Affordable Care Act, but declared unconstitutional the mandatory Medicaid eligibility expansion that the law's authors had expected would extend coverage to millions of currently uninsured Americans. Instead, the Court gave individual states the option to accept or decline the expansion, which, though far more generous with federal matching funds than the existing program, would still require states to spend more within already strapped budgets.

Medicaid Expansion map courtesy of Avalere Health via The Washington Post Wonkblog 5/5/13

In last month's Georgetown University Health Policy seminar, we discussed the complex role of the Medicaid state-federal partnership (which currently provides health insurance to 1 in every 5 Americans) in improving access to care and health outcomes. In fiscal year 2011, Medicaid spending totaled $414 billion, with two-thirds going to services for disabled elderly persons. Long-term care services (nursing homes, mental health, home health care) accounted for 3 in every 10 dollars that the program spent.

Currently, to qualify for Medicaid coverage, individuals must be not only poor, but belong to one of several "core eligibility groups" defined by federal law: children, pregnant women, people with disabilities, seniors, and adults with dependent children. Income thresholds vary widely across states, especially for working parents, who might find themselves eligible for coverage in more generous states but not in others. Few states provide significant coverage for non-disabled adults without dependent children, whose services were generally excluded from federal matching funds prior to the ACA.

In 2014, states that accept the ACA's Medicaid expansion will be required to extend eligibility to all adults (parents or not) earning less than or equal to 138 percent of the federal poverty level, which works out to annual incomes of $15,856 for an individual and $26,951 for a family of three. According to the Kaiser Family Foundation, more than half of today's 48 million uninsured have incomes below the new Medicaid threshold. In states that decline Medicaid expansion, there appear to be few feasible alternatives to leaving these persons without affordable coverage, except for those earning more than 100 percent of the federal poverty level who may be able to purchase subsidized private plans in state or federal health insurance exchanges. For example, in Florida, whose legislature rejected the Medicaid expansion last week against the wishes of Republican governor Rick Scott, only one quarter of the 1.3 million low-income residents who would have been covered by the expansion will be eligible for tax subsidies toward private coverage in the federal insurance exchange.

- Kenny Lin, MD
  Director, Robert L. Phillips, Jr. Health Policy Fellowship
  Department of Family Medicine
  Georgetown University School of Medicine