July 24, 2018

expert reaction to media reports that a Dutch drug trial of Viagra in pregnant women was stopped last week

A Dutch drug trial of viagra was stopped last week after more babies than expected were born with lung problems, and 11 have since died.

Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said:

What safeguards are put in place for clinical trials, and particularly for those involving pregnant women?

“Firstly the design of the trial is evaluated very carefully and requires approval by authorities.  There will need to be a good rationale to carry out the trial, but the outcome will be uncertain which is why the trial is done.  Great care is taken with trials involving pregnant women and drug companies are reluctant to do them which is why our knowledge of medicines in pregnant women is so limited.  Such trials are often carried out by academic groups rather than drug companies.

“Secondly, especially in important trials or where serious outcomes like death are being evaluated, there will be independent ‘Data Monitoring’ committees (DMC) that will evaluate the accumulating data on a regular basis knowing the treatments that were assigned (the investigators themselves may not know the treatments to avoid bias in the running or the assessment of the trials).  The DMC will advise those running the trial whether it should be continued or if they recommend stopping the trial.  It is often difficult to decide these questions but a DMC will usually act in a cautious way and their role is to protect participants in the trial.

How common are trials like this and how common is it for there to be unexpected outcomes?

“Trials is pregnant women are not as common as they should be, but they do occur, often with public funding.  All trials can have unexpected outcomes, which is precisely why the trial is done, because we do not know the outcome.  It is certainly not rare for a trial to be stopped early – sometimes because there is greater benefit than expected and sometimes because a harm occurs at a greater rate than anticipated.

“There have been other studies in this area, both involving preliminary work using animals and using pregnant women, and there was no indication that the treatment was dangerous based on previous research.

Are there regulations that people have to follow? Will they be the same in the Netherlands as in the UK?

“Yes there are EU and national laws that have to be followed and while details can be different in different countries, they follow the same principles.  The regulations and laws have increased in their scope, especially over the past 25 years.

If this was a trial being conducted on women known to have underperforming placentas, does that indicate what stage the trial was (e.g. Phase 1, 2 or 3)?

“This does not seem to be a drug company trial, and in pregnant women these phases of a trial are not as easily applicable.  In some senses it would be regarded as a Phase 3 trial.

“There are possible explanations for the differences seen that could be other than the effect of sildenafil, and the reason will require careful investigation.  It could be that higher risk women were given the sildenafil, but the DMC’s advice to stop the trial suggests that there was no obvious explanation other than the adverse effect of sildenafil.”

Declared interests

Prof Stephen Evans: “No conflict of interest.”