Evaluation of the Thalidomide Fetal Exposure Prevention Program (Thalidomide Survey)

Background

Thalidomide is a drug known to cause serious birth defects if taken during pregnancy. In 1998, FDA approved thalidomide under restricted distribution regulations. To minimize the risk of fetal exposure to the drug, the manufacturer, with FDA’s support and guidance, instituted the System for Thalidomide Education and Prescribing Safety (S.T.E.P.S.), a comprehensive risk management program directed at both physicians and patients. To assess the effectiveness of this program, the Slone Epidemiology Center conducted a patient survey. The original survey, initiated in 1998, was revised substantially in 2001, when the manufacturer initiated a modified S.T.E.P.S. program; both surveys are briefly described below.

Methods

From October, 1998, through July, 2001, the Slone Epidemiology Center conducted a survey that was mandatory for all patients (male and female) receiving the drug. Patients completed an enrollment questionnaire at the time of the first thalidomide prescription and follow-up questionnaires at subsequent office visits. The survey collected information on the patient’s understanding of the teratogenic risk of thalidomide and compliance with the measures required by the S.T.E.P.S. program. In addition, the survey included interventions with the patient and/or prescriber in instances where specific and potentially serious noncompliance was identified.

In the modified survey design conducted from 2001 through 2004, enrollment was voluntary. All patients (male and female) who received the drug were contacted and provided an opportunity to enroll. Questionnaires, targeted to specific pregnancy risk groups, were completed every two to four months during treatment and upon completion of treatment. To assess the representativensess of those who enrolled, we compared the characteristics of enrolled patients to those of unenrolled patients using information collected by the manufacturer as part of the S.T.E.P.S. program.

Results

26,655 patients were enrolled in the original (mandatory) survey. Less than half were female, and 6% of all enrollees were females of childbearing potential. No pregnancies were reported.

The modified (voluntary) survey enrolled 34,815 patients (approximately 47% of those contacted); 3% were females of childbearing potential. Knowledge of S.T.E.P.S. varied by age, primary language, and education, and tended to be highest among those age 30 through 79 years. Knowledge of the risks of thalidomide was highest among females of childbearing potential; women in this risk group did not report any pregnancies.

Investigators and Study Staff

Allen A. Mitchell, M.D., Principal Investigator
Carla M. Van Bennekom, R.N., M.P.H., Co-Investigator

Study Details

Source of Funding:

Celgene Corporation

Study Period:

1998 to 2004

Presentations

  • Van Bennekom CM, Mitchell AA. One country’s programs for preventing pregnancies in women exposed to teratogens: experiences with Accutane and thalidomide in the US. International Symposium on Prevention and Epidemiology of Congenital Malformations. Cardiff, UK, September 2000.
  • Van Bennekom CM, Mitchell AA. S.T.E.P.S. and the Accutane pregnancy prevention program: monitoring drugs with recognized teratogenic potential. Annual Meeting of Teratology Society. Keystone, CO, July 1999.
  • Van Bennekom CM, Mitchell AA. Thalidomide Survey. University of Utah Conference: Thalidomide: Impact on the Practitioner. Salt Lake City, UT, January 1999.

Publications

  • Andrews EB, Kaye JA, Van Bennekom C. The REMS publication paradox. Oncology (Williston Park) 2009;23(8):715-7.
  • Mitchell AA, Van Bennekom CM. Data we dare not present – do regulations prohibit learning from experience? [abstract]. Pharmacoepidemiol Drug Saf 2003;12:S66-7.
  • Van Bennekom CM, Mitchell AA. The voluntary thalidomide survey [abstract]. Pharmacoepidemiol Drug Saf 2003;12:S131.
  • Van Bennekom CM, Mitchell AA. Thalidomide: monitoring a unique regulatory approach [abstract]. Pharmacoepidemiol Drug Saf 1999;8:S158.