The Importance of Press Releases Describing ASH Conference Findings in Translating Research Into Policy: Case Study and Seven-Year Follow-up From a 2004 Oral Presentation

More than half of all “Black Box” warnings appear seven years after a drug receives Food and Drug Administration (FDA) approval, particularly for off-label utilization. In 1998, thalidomide received FDA approval for erythema nodosum leprosum. In 1999, a trial reported 30% response rates with thalidomide administration for refractory multiple myeloma. In 2004, an oral presentation at ASH by our group highlighted 28% rates of venous thromboembolism when multiple myeloma patients received thalidomide with dexamethasone or chemotherapy.

Case study and review of FDA documents related to the ASH presentation.

Aware of a 92% rate of off-label thalidomide administration, the Connecticut Attorney General (AG) monitored press releases related to thalidomide. After reading a university press release describing the 2004 ASH presentation's findings, the AG's office contacted the presenter. In turn, the study's principal investigator collaborated with the AG to draft a Citizen's Petition to the FDA requesting six safety-focused actions be taken related to thalidomide-associated VTE. The Petition was filed in 2005, and was the fourth Citizen's Petition of the FDA ever filed by a state AG (The other Petitions were denied). Two weeks later, FDA received a supplemental New Drug Application (sNDA) request from thalidomide's manufacturer requesting approval as treatment with dexamethasone for multiple myeloma. Over the next year, five internal consultations from FDA statisticians, safety experts, and regulatory personnel responding to the Petition were obtained. In October, medical officers from FDA's Office of Drug Safety concluded that they agreed with findings of increased VTE risks in multiple myeloma patients with thalidomide/chemotherapy or thalidomide/dexamethasone and prophylactic anticoagulation lessoned these risks. In 2006, FDA's Director of the Center for Drug Evaluation and Research informed the AG that four of the Citizen's Petitions six requests were granted as part of the sNDA approval. The sponsor revised thaliomide's “black box” warning and disseminated “Dear Doctor” letters advising of VTE risks when thalidomide-treated multiple myeloma patients received dexamethasone or chemotherapy and urged consideration of VTE prophylaxis. The sponsor also agreed to a post-approval epidemiologic study of VTE prophylaxis, although the protocol has yet to be agreed upon five years later. Seven months AFTER the label change, the manuscript describing our findings was published in JAMA.

Collaboration between the Connecticut AG and a hematologist, initiated in response to a press release describing a 2004 ASH conference presentation, using a the Citizen's Petition, a policy resource broadly available to health care providers, facilitated rapid translation of research into policy, although safety concerns persist.

Off Label Use: Thalidomide: erythema nodosum leprosum.