PharmacoEconomics

The FDA is a more than a century old agency created to guard public health in the United States. It was created to guarantee safety of food and cosmetic products as well as safety and efficacy of pharmaceuticals. The spectrum and magnitude of FDA’s activities makes it the largest public health protecting agency in the world. The FDA oversees more than $2 trillion in medical products, food and other consumer goods. The volume of FDA’s responsibilities continues to grow exponentially as new and innovative products and technologies come to the market. Fifty years ago, it was unthinkable to consider that the FDA will be assessing safety and efficacy of nanotechnology, genomics, stem-cell biology, and robotics products. Besides, globalization further expands the borders of FDA’s responsibility. More than 200,000 companies export food, cosmetics and medical products to the U.S. The necessity of cooperation with international partners overseas is urgent. In November 2008, a step was taken in that direction by opening an FDA office in Bejing, China.
This ever increasing workload requires substantial financial, technology and personnel resources. Unfortunately, the pace of Agency’s funding and modernization has not been keeping up with the innovation and modernization of the products it is supposed to assess. The FDA’s total budget is less than 75% of the budget of a school district in its home county in Maryland, while the agency’s IT budget is less than half of that of CDC. The relatively  recent highly publicized news with contaminated heparin, unsafe rofecoxib, contaminated peanut butter significantly reduced the confidence of the public in the FDA’s ability to perform its functions. Public opinion polls in 2006 showed that the ratings of public confidence in the FDA fell from 80% in 1970s to 36%, the level usually reserved for tobacco companies and used-car dealers.
One of the solutions to tackle the FDA’s inability of overseeing safety of such a broad range of products is restructuring of the agency. The proposed three separate divisions will include food safety agency, drug safety research and monitoring agency and an agency for a new drugs approval. In my opinion, the newly formed agencies will be able to approach their respective areas of expertise more efficiently. Having a much narrower area of responsibility than the current FDA has, the newly created agencies will have simpler and more targeted procedures to ensure timeliness and efficiency in protecting public health.

References

Hamburg M, Sharfstein  J. The FDA as a Public Health Agency. N Engl J Med. 2009;360(24):2493-2495.

Okie S. A To-Do list for the New FDA Commissioner. N Engl J Med. 2009;360(14):1373-1378.

Wood A. Playing “Kick the FDA” – Risk-Free to Players but Hazardous to Public Health. N Engl J Med. 2008;358(17):1774-1775.

Off-Label promotion of pharmaceuticals can be defined as promotion of drugs that are not approved by the FDA for a particular indication. Off-Label promotion is usually conducted by pharmaceutical companies through their sales force, detailing physicians on unapproved indications of selected products. According to the latest FDA guidance document on off-label promotion, companies can use articles published in scientific journals that describe the off-label use of their drugs in order to support their promotional claims. The guidance provides a more relaxed recommendation to the companies on how they can use off-label promotion. For instance, in its previous 1997 guidance, the FDA required companies to submit in advance their off-label promotional materials for review, and use them for products to be soon officially approved for a current off-label indication. Current guidance requires neither prior submission of materials for review nor submission of a supplemental new drug application.
Off-Label use of drugs comprises up to 21% of all prescribed medications and up to 50% of oncology drugs. Two most urgent issues to be addressed with off-label drug use are patient safety, and costs. Physicians rely on their clinical judgment and evidence from peer-reviewed articles to prescribe off-label. However, it is well known that publication bias and involvement of pharmaceutical companies in many published studies might provide biased evidence on off-label drug indication. Cost is another consideration when prescribing off-label. For example, unapproved use of expensive products with low evidence of effectiveness will lead to significant waste of resources. Off-label use of drugs may also pose a significant risk to safety and cost-effectiveness of treatment if the high costs of drugs are accompanied with harmful effects to patients. For example, results from a randomized trial by Tol et al, of previously untreated metastatic colorectal cancer showed that when cetuximab is added to a combination therapy of capecitabine, oxaliplatin, and bevacizumab, progression-free survival of patients with the add-on is 9.4 months vs 10.7 months (P=0.001) on the three-drug combination. As Frederic Curtiss, the editor-in-chief of the Journal of Managed Care Pharmacy, states in his recent editorial “the benefits of trial and error with chemotherapy should be carefully weighted against the potentially high costs – both the dollar cost of the chemotherapy drugs and the risk of adverse events.”
On the other hand, there are many benefits for more flexible drug use. It allows avoiding the backlog of FDA approval process while bringing the health benefits to the patients earlier. In pediatrics, for example, off-label drug use is of critical importance.
It is important to understand that the motivation matrices of pharmaceutical companies, payers, patients and physicians have a lot in common, but at the same time differ significantly in relation to off-label drug use. Pharmaceutical companies are primarily interested in expanding their markets and creating new demands for their products, payers are there to ensure cost-effective outcomes, while patients want to receive the best possible care and physicians to provide the evidence based treatment options. The regulatory system should be able to guarantee the necessary surveillance of the actions of the stakeholders involved while having patients’ safety as its highest priority.

References:

Food and Drug Administration. Guidance for industry on good reprint practices for the distribution of medical journal articles and medical or scientific reference publications on approved new uses of approved drugs and approved or cleared medical devices. Fed Regist. 2009;74(8):1694-1695.
Curtiss F, Fairman K. Contradictory Actions on Off-Label Use of Prescription Drugs? The FDA and CMS Versus the U.S. Justice Department. J Manag Care Pharm. 2009;15(2):161-165.
Gillick M. Controlling Off-Label Medication Use. Ann Itern Med. 2009;150(5):344-347.
Tol J, Koopman M, Cats A. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med. 2009;360:563-572.