In January 2005, the oversight responsibility of the Post-Approval Studies Program was transferred to the Division of Epidemiology (DEPI) of the Office of Surveillance and Biometrics (OSB)/Center for Devices and Radiological Health (CDRH).
The CDRH Post-Approval Studies Program encompasses design, tracking, oversight, and review responsibilities for studies mandated as a condition of approval of a premarket approval (PMA) application, protocol development product (PDP) application, or humanitarian device exemption (HDE) application. The program helps ensure that well-designed post-approval studies (PAS) are conducted effectively and efficiently and in the least burdensome manner.
CDRH has established an automated, internal tracking system that efficiently identifies the reporting status of active PAS studies ordered since January 1, 2005 based on study timelines incorporated in study protocols and agreed upon by the CDRH and applicants. This system represents CDRH's effort to ensure that all PAS commitments are fulfilled in a timely manner.
In addition, CDRH launched this publicly available webpage to keep all stakeholders informed of the progress of each PAS. The webpage displays general information regarding each PAS, as well as the overall study status (based on protocol-driven timelines and the adequacy of the data) and the applicant's reporting status for each submission due.
Five case-control studies will be conducted in Denmark, Germany, and the United Kingdom for 5 rare
disease outcomes: rare CTDs, rare neurological diseases, brain cancer, cervical/vulvar cancer and lymphoma. The round gel implants were introduced in Europe in 1985-1986, while the shaped gel implants have been in use in Europe since 2001, both for breast reconstruction and augmentation.
The studied diseases will be identified from a wide network of specialized medical centers, specialized institutions in major hospitals and health care centers in case of rare CTDs and rare neurological diseases as well as cancer registries or their associated tumor centers in case of brain, cervical/vulvar cancer and lymphoma. Controls will be obtained from randomly selected households. Overall, 1,150 cases (350-400 per country) and 5,000 controls (1,600-1,700 per country) will be enrolled into the study.
One large control group from the same neighborhood as cases will be used as a comparator for the studies.
These five case-control studies will investigate the risk of studied diseases in women with Mentor shaped and round silicone gel-filled breast implants compared to the risk of women who never had breast implants. Furthermore, the effect of any type of breast implant on the five studied diseases will be investigated.
The case-control studies will test the null hypothesis that women in Denmark, Germany and the United Kingdom with rare diseases studied are not more likely to have had exposure to Mentor¿s MemoryShape breast implants compared to women who do not have the rare diseases studied. The alternative hypothesis is that diseased women are more likely to have had exposure.
Study Population Description
Women in Denmark, Germany, and the United Kingdom with the studied rare diseases (i.e., rare
CTDs, rare neurological diseases, brain cancer, cervical/vulvar cancer and lymphoma) as cases and women without any of the 5 studied rare diseases from the same countries as cases.
Inclusion criteria for cases:
¿Alive at the time of enrollment ¿Between 22 and 60 years of age at the time of enrollment ¿Identified with one of the ICD10 codes included in the protocol for the 5 studied diseases ¿Valid histological or staging information (for cases with brain cancer, cervical/vulvar cancer and lymphoma
Exclusion criteria for cases:
¿Women with a history of malignancy, connective tissue disease or neurological disease at the time of diagnosis Women who either refuse to give permission to use their registry information, or do not live in the respective country or do not speak English, Danish or German, respectively
Inclusion criteria for the controls:
¿Between 22 and 60 years of age at the time of enrollment ¿Willing to provide the necessary information on their medical history (including the exposure to breast implants) and potential confounders
Exclusion criteria for cases: ¿Women who either refuse to give permission to use their registry information, or do not live in the respective country or do not speak English, Danish or German, respectively ¿Women with a history of any condition studied in the array of five case-control studies. ¿Women who provide unclear information that cannot be clarified by the interviewers
For each of the 5 case-control studies, 1,150 cases of women diagnosed with studied rare
disease identified from the specialized medical centers and cancer registries in Denmark, Germany and the UK will be enrolled. A total of 5,000 females identified from the same neighborhood as cases without any of the 5 rare disease outcomes will be enrolled as a control group to the 5 case groups.
Data will be collected by using questionnaires as well as electronic information provided by the
cancer registries/tumor centers. The same questionnaires will be used for cases and controls. The participating women will fill in the questionnaires on potential confounders (e.g., life-style related covariates) and exposure to breast implants. Similar questionnaires have been successfully used in previous case-control studies with self-administered questionnaires.
The documented information will include:
-Country code -Study site number -Case/control ID number -Date of birth -Age at menarche -History of pregnancies -Regular menstrual bleeding -Start of menopause -History of breast implant -Reason for breast implant (cosmetic, reconstruction, other) -Names, types, and dates for breast implants -Reasons for switch or stop of breast implant -History of hormonal contraception -History of hormone replacement therapy -History of infection with HIV, Helicobacter pylori, or EBV -Frequency of routine medical check-up in the decade before diagnosis of rare disease studied -Number of lifetime x-rays, including computerized tomography -Staging and histological information on lymphoma -Date of lymphoma diagnosis -History of other cancer -History of other severe diseases -History of treatment with immunosuppressive drugs -Family history lymphoma -Marital status -Educational level achieved -Professional exposure to radiation -Postal code as proxy for size of town or city -Body height -Body weight -Smoking status -Alcohol consumption -Level of physical exercise -Date of completion of questionnaire