The text below provides responses to CBER’s September 30, 2009 comments on the draft concept protocol (submitted to the BLA on August 13, 2009) for a phase IV epidemiological study to assess the incidence of autoimmune disease following administration of Cervarix. For ease of review, CBER’s comments are presented in bold text followed by GSK’s responses.
1) Please submit to us the actual or projected dates, as per 21 CFR 601.70(7), for the following:
- Date of Submission of Protocol
- Completion of Subject Accrual
- Submission of Annual Interim PMC Study Reports
- Completion of the Study
- Date of Submission of the Final Study Report
We are able to provide the following dates requested:
- Date of submission of protocol: March 2010
- Submission of Annual Interim PMC Study Reports: yearly after start of subject accrual.
- Date of Submission of the Final Study Report: 6 months after study completion.
The other dates (completion of subject accrual and completion of study) rely on rates of routine Cervarix uptake among the general population after licensure. Based on current Gardasil coverage rates (10-12%) among HMOs with a population of women of approximately 1.3 million aged 10-25 years and conservative assumptions for Cervarix coverage for the next years we believe we can complete subject accrual by March 2013 (3 years after final protocol). However, at present, it is difficult to confirm whether this target will be met, since it depends on rates of Cervarix uptake, which currently cannot be accurately predicted. Completion of study is targeted for 1.5 years after completion of subject accrual (i.e., September 2014, if subject accrual is complete by March 2013) and, as mentioned above, we expect that the study report could be provided 6 months after completion of the study (i.e., March 2015).
Once the study is initiated and after 6 months of subject accrual have been completed, we will be able to provide more accurate estimates of the dates for completion of the study and submission of the final study reports. In summary, we are suggesting the following dates:
Date of Submission of Protocol
Completion of Subject Accrual
Submission of Annual Interim PMC Study Reports
Yearly after start of subject accrual
Completion of the Study
Date of Submission of the Final Study Report
*contingent on subject accrual
2) Please submit a brief response to each item in the September 16, 2009, Information Request (see below).
Responses will be provided separately.
3) Please consider exchanging the pregnancy registry component of the PMC, with participation in VAMPSS (Vaccines and Medications in Pregnancy Surveillance System). VAMPSS uses both prospective surveillance and case control methods and is coordinated by the American Academy of Allergy, Asthma and Immunology.
Thank you for this suggestion; however, GSK has only limited knowledge of VAMPSS and therefore, we cannot commit to participation in VAMPSS in a timeframe commensurate with the initial licensure of Cervarix. We would therefore propose that the pregnancy registry component of the PMC be maintained.