Risks and Harms to Physicians Reporting Hematologic Adverse Drug Reactions (ADRs) to Health Authorities

Background : The Southern Network on Adverse Reports group (SONAR) has previously identified severe risks and harms to physicians who reported serious ADRs to Heath Authorities related to solid-tumor oncology pharmaceuticals. (eClinMed, PLOS One, Journal of Scientific and Professional Integrity) We investigated whether similar risks and harms occurred to clinicians/scientists who reported hematology-associated ADRS.

Methods: Quotes were abstracted from media coverage or Health Authority hearings for individual hematology drugs.

Results : Risks and harms were reported in regulatory agency or government agency meetings by eight clinician/scientists physicians who led phase-3 pharmaceutical-sponsored clinical trials (Olivieri N (U Toronto, NEJM 1996, Singh G, Stanford, unpublished 2004), Buse J (U of North Carolina, unpublished 1999, Henke M (Abteilung Universitatsklinik, Lancet 2003, Mangano D (UCSF, NEJM 2005), Topol E and Nissen S (Cleveland Clinic JAMA 2004), meta-analyses (n = 2) (Bennett C (Northwestern, JAMA 2008, Mangano D (UCSF, NEJM 2006); database analyses (n = 1) (Mangano D (UCSF, NEJM 2004), case-control studies (n = 1) (Brass L, Yale, NEJM 2005) and an independent safety review (n = 1) (Solomon S, Harvard, JAMA 2005) including lawsuits, loss of job, public harassment and loss of grants. Three physicians lost academic positions (Topol, Olivieri, Mangano), two physicians lost federal grants (Olivieri, Bennett), and one FDA scientist (Graham) was demoted. ADR findings resulted in drug removal (n = 7; Vioxx, Avandia, Bextra, Celebrex, Trasylol, Phenyl propanolamine, Hydroxy-ethyl starch), revised indications (n = 2) (Procrit, Aranesp 2007, 2008, 2010)) or 10-year delay in FDA-approval (n = 1) (Fereprox). Median time from FDA approval to ADR identification was 8 years (Range, 4 years (Bextra) to 62 years PPA)). Numbers of persons reportedly seriously injured or dying from 1 ADR was 10,00 (Procrit)- 270,000 (Vioxx) (median 120,000). Manufacturer allegations that resulted in pharmaceutical companies actions included violation of secrecy agreement (n = 2) (Fererpox, PPAs) and public reporting of proprietary data (n = 11). Pharmaceutical companies paid $600,000 (Fereprox) to $5.8 billion (Vioxx) in fines and settlements.

Discussion: Twelve physicians experienced severe threats and/or harms after reporting hematologic-associated ADRs to Health Authorities and/or in major publications. We suggest physicians not sign secrecy agreements that might jeopardize public safety (as currently established by almost all US medical universities) and should partner with independent drug safety monitoring boards (DSMBs) on ADR evaluations to monitor safety concerns of drugs and medical devices.

No relevant conflicts of interest to declare.