The Impact of Emerging Safety and Effectiveness Evidence on the Use of Physician-administered Drugs

Abstract

Background Spending on physician-administered drugs is high and uses not approved by the U.S. Food and Drug Administration (FDA) are frequent. While these drugs may be targets of future policy efforts to rationalize use, little is known regarding how physicians respond to emerging safety and effectiveness evidence. Study objective We analyzed changes in bevacizumab (Avastin™) use for breast cancer in response to its market launch (Feb-2008), two FDA meetings reviewing data suggesting that its risks exceed its benefits (July-2010, June-2011), and the FDA’s withdrawal of approval (Nov-2011). Data Data from a population-based audit of oncologists’ prescribing (IntrinsiQ Intellidose) were used to measure the monthly number of breast cancer patients treated with bevacizumab January, 2008-April,2012. Methods The number of bevacizumab patients following each regulatory action was estimated using negative binomial regression, compared with patients before the first FDA meeting, adjusting for cancer stage, treatment line, patient age and outpatient office affiliation. Results Bevacizumab use for breast cancer increased significantly after FDA approval. Following all regulatory actions, there was a 65% decline (95%CI=64%-65%) in use compared with the period before the first meeting. The largest decline was in the six-month period following the first meeting (37%, 95%CI=28%-47%). The rate of decline did not differ by patient or cancer characteristics and differed minimally by office affiliation. Discussion Bevacizumab use for breast cancer declined dramatically after FDA meetings and regulatory actions, a period without changes in guideline recommendations or insurance coverage. Physicians appear responsive to emerging evidence concerning physician-administered drug safety and effectiveness.

Stimulated Reporting: The Impact of US Food and Drug Administration-Issued Alerts on the Adverse Event Reporting System (FAERS)

“…Challenges to using FAERS data, however, have been reported to include under-reporting [ 11 , 12 ], the “Weber Effect” [ 13 , 14 ], and “stimulated reporting” [ 15 – 19 ]. With regard to under-reporting, while it remains a significant limitation, recent efforts by the FDA, global regulatory agencies, and the healthcare industry itself are helping to increase AE reporting rates.…”

“…To help guide prescribing decisions and arm healthcare professionals with emerging post-marketing safety risks, the FDA issues warnings [ 7 , 18 , 25 ], which have often effectively modified prescribing behaviors [ 17 , 19 ]. However, the alerts are sometimes challenged by the scientific community [ 17 , 26 – 29 ], numerous alerts can be required to trigger an effect [ 30 ], and too often they have little to no impact on prescribing patterns [ 17 , 28 , 31 – 33 ].…”

“…Although a number of studies have evaluated the impact of FDA alerts on drug use [ 16 – 19 , 31 , 33 , 40 – 57 ], few have comprehensively studied the impact of FDA alerts on AE reporting. Past studies that have found evidence for stimulated reporting with regard to post-marketing AE data have generally examined solitary, or a single group of, drugs.…”

Regulatory withdrawal of medicines marketed with uncertain benefits: the bevacizumab case study

“…A small majority (52 %) agreed with the FDA decision to withdraw the indication on the ground that the benefits shown in the two additional studies with bevacizumab were not of the same amount observed in the initial E2100 trial but 48 % believed this was not a valid reason. Another study examined trends in use of bevacizumab for breast cancer in 122 oncology practices involving 570 oncologists in the US [ 34 ]. It found that the use declined by 37 % between May 2010 (just prior to the ODAC meeting revoking approval) and November 2010 (just prior to the start of the FDA withdrawal process) and by 63 % just prior to the FDA official withdrawal notice without concomitant changes to clinical guidelines or insurers’ coverage policies that may explain these trends.…”

Bevacizumab in the neoadjuvant treatment of human epidermal growth factor receptor 2‑negative breast cancer: A meta‑analysis of randomized controlled trials

“…Bevacizumab (Bev) was the first vascular endothelial growth factor (VEGF)-A inhibitor to be studied in breast cancer and other solid cancers (10–14), and is currently approved by the USA Food and Drug Administration (FDA) for use in several cancer types (12–14). Following provisional approval for use in metastatic breast cancer in the USA, the FDA subsequently revoked approval in November 2011, due to the risks of Bev therapy outweighing the benefits (15,16). Currently, Bev is only approved for the treatment of breast cancer outside the USA.…”