HESI Developmental and Reproductive Toxicology Committee Survey: Contraception in Clinical Trials
Objective: to understand the current industry practices for contraception requirements for both women and men in clinical trials, the
governance processes set up to promote consistency and/or compliance with contraception requirements, and the effectiveness of current
contraception practices in preventing pregnancies during clinical trials. This effort should also identify opportunities for improvements in current
practices.
Acronyms:
WCBP: women of child bearing potential
bHCG : human chorionic gonadotrophin
COC: combined oral contraceptive – i.e. combined estrogen and progestagen ingredients.
EFD – embryofetal development
HRT – hormone replacement therapy
DDI – drug-drug interaction
Definitions:
For survey purposes, company “guidance” includes any or all of the following – policies, standards, SOPs, procedures, written guidance
documents.
Instructions for filling out survey
There are 5 sections to this survey which are likely to require contributions from multiple functions. Where possible, please provide (e.g.
embed) anonymized source guidance documents or the critical text from source documents. Please use comment boxes as desired to add any
detail considered pertinent.
If you have questions, please contact either
USA: William Breslin, breslin_william_j@lilly.com, 317-433-3601
Europe: Jane Stewart, jane.stewart@astrazeneca.com, +44 1625 513209
Please send completed survey to: Connie Chen, cchen@hesiglobal.org by March 31, 2012. Partially completed surveys are of use – thank
you!
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HESI Developmental and Reproductive Toxicology Committee Survey: Contraception in Clinical Trials
Company:
CODENAME:
A. Company guidance for contraception and/or barrier protection for male subjects with partners of childbearing
potential.
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Is there company guidance for contraception or
barrier protection requirements for men in clinical
trials?
If contraception or barrier protection use is specified,
how is the duration of post-trial contraception
determined?
Is double barrier protection ever required?
Are 2 forms of highly effective contraception ever
required? If so, under what circumstances.
Are there company restrictions or guidance for
enrolling men with pregnant partners?
Do contraception and barrier protection requirements
differ between small molecule and biologic drugs?
Any other comments:
Yes/No
Please summarize key requirements and governance process
Please describe.
Yes/No, If yes, under what circumstances.
Yes/No, If yes, under what circumstances.
Yes/No. If yes, please describe.
Yes/No. If yes, please describe.
B. Company guidance on management of WCBP in clinical trials
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Is there a company-wide definition of a WCBP?
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Is there company guidance on birth control
requirements for WCBP in clinical trials?
If contraception or barrier protection use is specified,
how is the duration of post-trial contraception
determined?
Is there company guidance that details the birth
control methods considered acceptable for use?
E.g., male condom, COCs, copper-banded IUD etc
Do contraception requirements differ between small
molecule and biologic drugs?
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4
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No / Yes
Please provide WCBP definition
No/ Yes, If yes, please describe the basic requirements and governance process.
Please describe
No/ Yes
Please provide list of recommended methods
Yes/No. If yes, please describe.
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HESI Developmental and Reproductive Toxicology Committee Survey: Contraception in Clinical Trials
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Pretrial enrollment procedures:
a) Does policy require pregnancy testing before
enrollment of all WCBP on clinical trials?
a) No/Yes
b) If yes, what are the technical detail regarding
timing and type of pregnancy testing (e.g. urinary
versus serum bHCG, time before first dose) are
specified?
b) Please provide technical details
c) Are there exceptions regards requirements for
pretrial pregnancy testing?
c) Describe exceptions
d) Is confirmation of a menstrual period required
prior to trial entry?
d) Yes/No
e) What other conditions are specified pre-trial to
ensure WCBP are not pregnant?
e) Provide other criteria
f ) What information is given to WCBP on the
acceptable birth control methods for the clinical trial?
During trial & post trial procedures
a) Is pregnancy testing typically or rarely required
during dosing in a clinical trial?
f) Provide example of the typical information
b) Is ongoing birth control compliance monitored?
b) Yes/No rarely. If rarely, describe circumstances.
c) At checks in a clinical trial, are WCBP routinely
asked to reconfirm compliance regards birth control
requirements for that trial?
c) Yes/No, If yes, please describe monitoring procedure.
d) What pregnancy testing is typically required after
cessation of dosing?
d) Yes/No, Describe
a) Yes/No typically.
Any other comments:
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C)
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2 i)
3 ii)
4 iii)
5 iv)
6 v)
7 vi)
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Influence of Animal Data on birth control requirements on clinical trials
Is there policy / guidance on what developmental
toxicity animal data should be available before
WCBP are enrolled in clinical trials?
When / if proceeding into WCBP clinical trials without
EFD studies in 2 species, what difference (if any)
does that make to birth control or pregnancy testing
on the trial?
For WCBP on trials, when animal data illustrates
potential for fetal harm at clinical exposures, what
difference (if any) does that make to birth control or
pregnancy testing on the trial?
For men on trials, when animal data illustrates
potential for fetal harm at clinical exposures, what
difference (if any) does that make to birth control
requirements on the trial?
For men on trials, when animal data illustrates
potential for testicular toxicity at clinical exposures,
what difference does that make to informed consent
and birth control requirements on the trial?
When the embryo/fetal and male and female fertility
data indicate no risk, does this information impact
contraception requirements for men or WCBP?
Does the margin of safety for embryo/fetal toxicity
impact contraception requirements?
Other comments:
No / Yes
If Yes, please describe default and any key exceptions to that default.
If yes, is the guidance different for small molecules vs. biologics?
Yes/No. If yes, please explain.
Yes/No. If yes, please explain.
D) Drug-Drug Interaction work to support hormonal contraceptives / HRT
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2
Is there company guidance on the DDI testing
required prior to allowing use of systemic hormonal
contraceptives?
What default testing for DDI is required?
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No / Yes
Please summarize key aspects
Please describe the in vitro/in vivo test cascade
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HESI Developmental and Reproductive Toxicology Committee Survey: Contraception in Clinical Trials
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Would a final submission package generally include
a DDI study with ethinylestradiol/COC?
If not, what would trigger need for a specific DDI
study with ethinylestradiol or a COC?
What criteria are used to determine if a DDI signal is
of sufficient magnitude to be of concern regards
either COC efficacy ( decreased exposure to
estrogen component) or COC / HRT safety (e.g.
increased exposure to estrogen component)
Any other comments:
Yes / No
No, describe trigger
Describe criteria for decreased exposure:
Describe criteria for increased exposure:
E) Reporting and Review of Pregnancies in Phase I – Phase III Clinical Trials
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Is there company guidance on reporting and follow
up on inadvertent pregnancy drug exposure in
WCBP in clinical trials?
What is the reporting mechanism?
No
Yes – provide key aspects of guidance & reporting mechanism
2
In clinical trials where the men were requested to
use contraception, is there company guidance on
reporting and follow up of pregnancies in WCBP
partners?
What is the reporting mechanism?
Yes/No
If yes – provide key aspects of guidance & reporting mechanism
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Reported pregnancies
What information is gathered about the (failed) birth
control method?
What other information is typically gathered about
the exposed pregnant patient (e.g. primagravida etc)
Review of Pregnancy rates in trials including
WCBP
a) Is there a routine review of reported pregnancy
rates at the end of trials?
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b) Is there a review of reported pregnancy rates at
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a) Yes/No
b) Yes/No
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the end of trials with test agents considered likely to
cause fetal harm?
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c) What (if any) oversight of the pregnancy rates
across multiple trials is undertaken (egg internal
ethical review board on an annual basis?)
c) Describe
d) Is there a review of pregnancy rates with drugs
that have a DDI with hormonal contraceptives?
d) Yes/No
e) Are pregnancy rates summarized by geographical
area or country to understand the cultural impact on
contraception practices and effectiveness?
e) Yes/No. If yes, did this review prove informative; explain.
Any other comments:
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