Advisory Committee for Reproductive Health Drugs
September 29, 2003
Questions
- Please discuss what enrollment
criteria should be used to adequately capture the population to be studied
for ovulation induction, and for ART.
- Should enrollment be stratified by age
for ovulation induction, and for ART?
- Should we stratify by use of adjunct
procedures, such as donor oocyte or ICSI?
- Should studies be blinded or not? If blinded, discuss the merits of
blinding the assessor, the patient, or both.
- Discuss the merits of having placebo
and/or active control arms in studies.
If an active control is used, discuss how you would define the
non-inferiority margin.
- Discuss the advantages and
disadvantages of single versus multiple treatment cycles.
- Discuss the advantages and
disadvantages of powering studies to detect a difference in live birth
rate, or in ongoing pregnancy rate.
- If studies can not be powered to
demonstrate differences in live birth rate or ongoing pregnancy rate,
discuss the clinical relevance of the following surrogates.
Rate of patients with:
Presence of fetal
heartbeat
Presence of gestational
sac
Positive β-hCG
Ovulation rate
Follicular development
rate
- Is an intent-to-treat analysis
appropriate for ovulation induction?
If not, should cycles be analyzed per patient given hCG?
- Is an intent-to-treat analysis
appropriate for ART? If not, should
cycles be analyzed per retrieval, or per embryo transfer?
- Please discuss which safety endpoint(s)
should be evaluated.
- Drug manufacturers conducting studies
for female infertility currently obtain the following indications:
- Induction of ovulation and pregnancy
- Multiple follicular development in
ART
Please comment on the appropriateness of these
indications given your discussions of endpoints and analyses.
- Should manufacturers who obtain
approval for ovulation induction or ART maintain a pregnancy
registry? If yes, what information
should be collected? At what point
should the registry be terminated?