Drug Safety Oversight Board Meeting, April 15, 2010
The Executive Director updated the Drug Safety Oversight Board (DSB or Board) on Drug Safety Communications posted and in development since the March 18, 2010 meeting. The following is a list of the posted risk communications:
Drug Safety Communications Posted since the March 18, 2010 DSB meeting:
- March 19, 2010: Ongoing safety review of high-dose Zocor (simvastatin) and increased risk of muscle injury
- March 31, 2010: Ongoing safety review of Stalevo (entacapone/carbidopa/levodopa) and possible development of prostate cancer
- April 7, 2010: Follow up to the Public Health Alert about changes to the heparin sodium USP monograph
The DSB discussed two topics:
- CT scans, radiation exposure, and cancer risk
- Bisphosphonates and a potential risk of atypical femoral shaft fracture
The views expressed by non-CDER employees are those of the individual and not necessarily the opinion of their respective government agency.
CT scans, radiation exposure, and cancer risk
A CT scan, also called computed tomography, is a diagnostic procedure that uses special X-ray equipment. It combines a series of X-ray views taken from many different angles to produce cross-sectional images of the body.
More than 19,500 CT scans are performed in the United States every day. One CT scan can expose a patient to radiation equivalent to approximately 30 to 442 chest X-rays. There were an estimated 72 million CT scans conducted in the U.S. in 2007.1-3 Using risk models based on the National Research Council’s “Biological Effects of Ionizing Radiation” report and organ-specific radiation doses derived from a national survey, Berrington de Gonzalez and colleagues estimated that approximately 29,000 (95% CI, 15,000-45,000) future cancers could be related to CT scans performed in the US in 2007.1 The application of consensus radiation risk estimates strongly suggests that increased exposure to ionizing radiation from CT scanning may have significant public health implications.
The Federal Partners with hospitals and clinics presented information on the number of CT scans ordered for a particular indication (e.g., diagnostic, screening) and age group. The Board also invited a guest expert, Dr. Charles Anderson, Chief of Radiology for the Veterans Health Administration (VHA). Dr. Anderson shared data regarding X-ray and CT testing trends at the VHA.
The Center for Devices and Radiologic Health (CDRH) and the Center for Drug Evaluation and Research (CDER) share the regulatory authority related to CT Scans. CDRH regulates the CT scan equipment and CDER regulates the imaging contrast agents. The contrast agents are often used during medical imaging to highlight specific parts of the body.
The Board discussed the following:
- An overview of the publications, reports, meetings, and events on the ionizing effects of radiation from CT Scans that have been issued or occurred since June 2005
- Highlights from high profile incidents of radiation over-exposure occurring during CT brain perfusion scans
- The risks and benefits of medical imaging involving radiation exposure, including a distinction when the imaging is for diagnosis of symptoms versus screening of asymptomatic patients
- Radiation risk estimates from the Biologic Effects of Ionizing Radiation (BEIR VII) report
- An overview of FDA’s initiative to reduce unnecessary radiation exposure from medical imaging
- Highlights of the extent and limitations of the authority of CDRH in reducing unnecessary radiation exposure from medical imaging devices
- CDER’s radiation safety responsibilities for imaging drugs
- The available data about the risk of cancer related to radiation exposure from CT scans and the additional data needed to better understand these risks
- FDA’s role in influencing the safe use of CT scans
- The best way to communicate FDA’s recommendations about the safe use of CT scans to healthcare professionals and the public
- Berrington de Gonzalez A, Mahesh M, Kim KP, et al. Projected Cancer Risks From Computed Tomographic Scans Performed in the United States in 2007. Arch Intern Med. 2009;169(22):2071-2077
- Smith-Bindman R,Lipson J, Marcus R, et al. Radiation Dose Associated With Common Computed Tomography Examinations and the Associated Lifetime Attributable Risk of Cancer. Arch Intern Med. 2009;169(22):2078-2086
- Redburg, RF. Cancer Risks and Radiation Exposure From Computed Tomographic Scans: How Can We Be Sure That the Benefits Outweigh the Risks? Arch Intern Med 2009;169:2049-50.
Bisphosphonates and a potential risk of atypical femoral shaft fracture
Bisphosphonates are a class of drugs that prevent the loss of bone mass. They are commonly prescribed to prevent or treat osteoporosis in postmenopausal women. Osteoporosis is a systemic disease characterized by the thinning of bone tissue and loss of bone density over time. The Board discussed whether patients using bisphosphonates have an increased risk of atypical subtrochanteric femur fractures –fractures in the bone just below the hip joint.
The Board invited a guest expert in osteoporosis research, Dr. Cliff Rosen, from Maine Medical Center’s Research Institute. The Federal Partners with hospitals and clinics provided bisphosphonate usage patterns including information on femur fractures occurring in their patient population using bisphosphonates.
The Board discussed the following:
- Overview of osteoporosis pathophysiology and treatment goals
- The National Osteoporosis Foundation 2008 established osteoporosis screening and treatment guidelines
- Bisphosphonate drug utilization trends in the U.S.
- Mechanism of action for bisphosphonates
- Efficacy and safety of bisphosphonates
- The American Society of Bone and Mineral Research’s draft definition of subtrochanteric femoral and hip fractures
- Data on the occurrence of subtrochanteric femoral fractures in patients using bisphosphonates from several large observational registry-based studies
- A recently published study (The FLEX trial) on the long term use of bisphosphonates
- The additional data needed to better ascertain whether bisphosphonates are associated with an increased risk of subtrochanteric femoral fractures
- Recommendations regarding future drug safety communications about bisphosphonates and a potential risk of atypical fractures
Board Update: A Feedback Conversation
The Board discussed a possible Drug Safety Communication involving a diphenhydramine over-the-counter product intended for topical use that consumers mistakenly ingested orally.