FDA Drafts Guidance for Consideration for Inclusion of Pregnant Women in Clinical Trials – Part 3


In Part 1 of our blog series about Food and Drug Administration (FDA)’s draft guidance entitled Pregnant Women: Scientific and Ethical Considerations for Inclusion in Clinical Trials: Guidance for Industry, we discussed the introduction and background, and in Part 2 we discussed ethical considerations. Now in Part 3, we will discuss other considerations for enrolling pregnant women in clinical trials.

Disease and availability of treatment options:

Prior to enrolling pregnant women in a trial, the sponsor should consider:

  • Severity of the pregnant woman’s disease or condition.
  • How rare the disease or condition is.
  • Availability of other treatments for the disease or condition.
  • Individual pregnant woman’s situation.
    • For example: failure of other viable treatment alternatives for a life-threatening condition.

When to enroll:

  • Animal reproductive toxicity studies should be conducted prior to enrolling pregnant women in clinical trials.
  • Phase 1 and 2 clinical trials should be completed and safety data collected from non-pregnant women of reproductive age.
  • Sponsors should consider some criteria prior to enrolling pregnant women:
    • Evidence of safety data based on other indications or a lack of alternate therapies - pregnant women may benefit from enrollment.
    • Availability of other treatments or a lack of safety data – enrollment of pregnant women may increase risk over benefit.

Pharmacokinetic Data:

  • Physiological differences may occur during pregnancy that alter the metabolism, absorption, distribution, and/or excretion of drugs.
  • Pharmacokinetic data (PK) on pregnant women should be collected in phase 2 trials on investigational products to better calculate appropriate dosing for phase 3 trials.
  • PK data should also be collected in phase 3 trials on marketed products.
  • Computer modeling and simulation of PK in pregnant woman may be helpful.

Safety Data Collection and Monitoring:

  • Data that should be collected for safety include.
    • Gestational age of fetus at enrollment.
    • Length of time fetus exposed to treatment.
    • Outcomes after pregnancy.
    • Follow-up safety data on infant.
  • Specialized monitoring can include:
    • Supervision by medical expert such as obstetrician.
    • Cord or infant blood samples to determine drug blood levels.
    • Specialists knowledgeable about pregnant women and fetal. concerns should contribute to the data monitoring plan so that adverse events are appropriately reported and monitored.

Stopping Criteria:

Just as in typical clinical trials, there may be considerations for stopping a trial. Some examples are:

  • Active treatment is superior to the control.
  • Analysis of study data determines that risks outweigh the benefits.

Enrolling pregnant women in clinical trials requires careful use of risk-benefit analysis. Clinical trial design should minimize risks while still maintaining the ability to address the hypothesis. Pregnant women and their fetuses may benefit, either directly or indirectly, through inclusion in clinical trials. The draft guidance released by the FDA addresses considerations for including pregnant women in clinical trials while minimizing risks. The public comment period is open until June 08, 2018, and instructions for submissions of comments can be found here.

- The Clinical Pathways Team

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