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Some Thoughts on Pharmacovigilance and Postmarketing Surveillance

2016; Elsevier BV; Volume: 38; Issue: 12 Linguagem: Inglês

10.1016/j.clinthera.2016.11.008

1879-114X

Richard I. Shader,

Pharmaceutical Economics and Policy

As college students in the early 1950s, many of us were deeply involved in following politics. Some of us campaigned for Adlai E. Stevenson II despite being strong admirers of Dwight David Eisenhower (Ike), who in our eyes was a great hero. Others considered Stevenson to be too much of an “egghead.” As I recall, Ike was the first to seriously court the women’s vote. Among the issues on our minds in those years were McCarthyism and the so-called Red Menace, the Korean War, our relationship with NATO, and our involvement in Latin American politics. Nixon, Ike’s running mate, came under a cloud during the campaign when he was accused of personally profiting from gifts given by wealthy donors. The Ike-Nixon ticket pulled ahead of Stevenson when Nixon explained that one of these gifts was a dog called Checkers, a gift he refused to return because his daughter Tricia loved and had named the dog. The outcome of this election was attributed, in part, to Nixon’s “Checkers” speech, an appeal to sentiment that was irrelevant to the governance of the United States. I still treasure my silver, bottom-of-a-shoe-with-a-hole-in-the-sole tie pin, the signature of the Stevenson campaign. Another movement also captured our attention, the Ku Klux Klan (KKK). Some of us initiated an informal discussion group. Although we were diverse in membership, we were united in our dislike of the KKK and what it stood for in our eyes—anti-Semitism, anti-Catholicism, anti-immigration, white supremacy, and nativism. I had come from Central Florida, an area that was known for its KKK activities, especially in the 1930s through the 1950s. Another member of our group, a history major, was from the state of Washington, where the KKK had been strong in the 1920s and 1930s. He told us about a weekly publication from that era called Watcher on the Tower. Originating in Seattle, it emphasized the role of the KKK as keepers of white supremacist values and protectors of America.1Seattle Civil Rights & Labor History Project. Watcher on the Tower and the Washington State Ku Klux Klan. http://depts.washington.edu/civilr/kkk_wot.htm. Accessed October 9, 2016.Google Scholar In 2016, some of this may sound disturbingly familiar. Tongue in cheek, we decided to call ourselves The Society of Watchers of Tower Watchers. A Germanic languages major in our group wanted us to use the name Gesellschaft der Wächter von Turmwächter. Other than as a way to come together for support and to share thoughts and information, we Watchers of Tower Watchers really did not expect to accomplish anything. Young and idealistic, we were a lot of talk, a vigilant surveillance group without a plan or capacity for action. This month’s topic is devoted to another area of vigilance, pharmacovigilance. Pharmacovigilance requires cautious watchfulness and careful surveillance. Only in this way can signals of unanticipated harmful properties be detected during the postmarketing phase of drug development. Currently, various pathways are available to accelerate approvals for many new chemical entities (NCEs). As a result, it is less common now for sufficient numbers of patients to be studied before marketing to understand fully the pharmacology of these new NCEs. Many Phase III development plans do not call for more than 3000 to 5000 patients to be exposed to a NCE. This means that unwanted effects that occur in fewer than 1 in 5000 patients will likely go undetected before an approval letter from the Food and Drug Administration (FDA). Similarly, the information obtained from studies of new biologics is likely to be incomplete, particularly because their complete pharmacology is not typically known at the time of marketing for their first indication. Safety and efficacy are key elements of a New Drug Application (NDA); benefit must prevail over risk. In 2007 in its reauthorization of the FDA, Congress passed the Food and Drug Administration Amendments Act (FDAAA). To improve the likelihood that a NCE’s or biologic’s risks would be outweighed by its benefits, FDAAA gave the FDA the legal authority to require that manufacturers develop Risk Evaluation and Mitigation Strategies (REMS).2Approved Risk Evaluation and Mitigation Strategies (REMS). http://www.accessdata.fda.gov/scripts/cder/rems/index.cfm. Accessed October 9, 2016.Google Scholar REMS can be required either as part of an agent’s approval or even once it is already on the market. That occurs if a signal has emerged, and yet it seems worthwhile to continue the drug’s availability for patients who benefit from the product. REMS can be quite varied, ranging from the distribution of medication guides (patient package inserts), to specific training for prescribing clinicians, to conducting new clinical studies that focus on the matter of concern.3REMS Template. http://www.fda.gov/downloads/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm188155.pdf. Accessed October 9, 2016.Google Scholar Our Guest Editor for this topic is our new Consulting Editor for Pharmacovigilance and Pharmacoepidemiology, Paul Beninger, MD. Paul is also vice president and senior medical advisor, Global Safety Science, Global Pharmacovigilance and Epidemiology at Sanofi as well as an assistant professor and director of the MD/MBA Program in the Department of Public Health and Community Medicine at Tufts University School of Medicine. We are extremely pleased that Paul has joined our editorial team and that he will bring his vast expertise into our reviewing process. For this issue, Paul has assembled three contributions that provide a background for understanding where we are today and what the future may hold.4Beninger P. Pharmacovigilance in the new millennium.Clin Ther. 2016; 39 (2512–2513)Google Scholar, 5Beninger P. Ibara M. Pharmacovigilance and biomedical informatics: a model for future development.Clin Ther. 2016; 39 (2514–2525)Google Scholar, 6Wu J. Juhaeri J. The US FDA’s Risk Evaluation and Mitigation (REMS) program – current challenges and future direction.Clin Ther. 2016; 39 (2526–2532)Google Scholar, 7Price J. What can big data offer the pharmacovigilance of orphan drugs?.Clin Ther. 2016; 39 (2532–2545)Google Scholar