No clinical trials on pregnant women -> discrimination?

[deepwatersolo]

I don't have much time the next couple of days, but I stumbled over a thread on Twitter have to leave this here, as it struck me (and frankly irritates me to no end) and I'd appreciate outside perspective.

Science journalist Erin Biba on Twitter makes a good point about women having long been ignored by medical studies.
twitter.com/erinbiba/status/1115337518294228993

'Wanna hear something crazy? It wasn't until 2016 that the National Institute of Health required that medical research include male AND female mice as well as male AND female tissue cells in drug development. Before that female mice and female tissue cells didn't need to be used. The NIH also didn't require that women be included in clinical trials for drugs until 1993.'

But then goes on to say:
'Currently there are NO clinical trials for any drug done on pregnant women. Pregnant women are excluded from ALL clinical trials. If a woman in a clinical trial becomes pregnant she must exit the trial.'

And finishes with :
'If you're wondering why women are so susceptible to snake oil and pseudoscience there's your answer. It's because medicine has ignored their health and they're desperate for any possible treatment.'

I cannot overstate, how galling I find it, to bring the issue of 'no trials on pregnant women' into this and imply they are overlooked. Fetal development is quite sensitive to drugs, and I doubt any well informed woman who is not desperate for money would risk this, considering she will probably be stuck with the consequences this may have on her pregnancy & resulting child.

From my perspective it very much looks like an upper class woman - who would never dream of participating in such a trial when pregnant, because risks are too high - bemoans the fact that less privileged and informed women aren't persuaded to play guinea pig for her.

(Also, are women actually so disproportionall susceptible to snake oil? That comment also rubbed me the wrong way. )

Am I getting this wrong? Am I reading too much into this?

Don’t know, but a counter argument could be:

It could make the trial results difficult to interpret ..the results from pregnant women could be different for many reasons, so it’s creating risk without gain in understanding ( unless you have quite a few or pregnant women) .

Also, it is running trial on mother and baby. Do you propose that poor children should also be able to sign up?

Finally, if you allow it, women will assume that it is likely to be safe for baby or it would not be allowed, so they may make false judgement?

Seconded MIdgebabe. All very good points.

I can't imagine many pregnant women would sign up for a trial particularly if the drug is not specifically for pregnant but just for high blood pressure that may affect pregnancy.
This isn't pregnant women being excluded it's pragmatism by the trial organisers. Pregnant women would have to be a separate subgroup in the trial and you wouldn't get enough of them.
Most people participate in trials through either altruism or desperation. Pregnant women will put their foetuses first and not want to be experimented on.

Sounds sensible not to have clinical trials on pregnant women. Doesn't sound like discrimination but more like ethical.

She's wrong. Pregnant women aren't excluded from all drug trials, but obviously there needs to be a clear case that the benefits outweigh any potential risks to the woman or the fetus, so in practice the number of trials is small.

I can’t imagine many pregnant women willingly testing drugs with potential side effects for their baby.

I’ve just had a baby and there’s no way I’d have participated in a drug trial whilst pregnant.

She appears to suggested that pregnant women should be routinely included in clinical trials which is of course nonsense. A woman who becomes pregnant while taking an experimental drug will always be asked to stop it. Why would they put the health of the baby at risk with an unproven drug? That would be utterly unethical.
The only correct way to test drugs on pregnant women if needed is if they have already been proven to be safe and effective in both adults and children. You'd never include pregnant women in an initial trial. She doesn't understand how clinical trials work.

She doesn't understand how clinical trials work.

It very much looks like it.

I don't think you can have clinical trials on pregnant women, because of the ethics of affecting the fetus.

But then, once a drug passes, it's going to be out in the wild, and will inevitably end up being used on pregnant women (ie ones using it who then become pregnant) - so you end up with the situation that instead of a small number of women becoming pregnant whilst on the trial, being carefully monitored and tested for issues, there is a much larger number of unmonitored pregnant women now taking this drug.

Which seems insane and dangerous

So now I come back to the idea, that at a bare minimum, women becoming pregnant on the trial should stay in the trial - because the alternative is worse.

late stage trials obviously

There are pregnancy specific medical trials which women obviously take part in to try and improve maternity care.

But for general drug trials it's not necessary or ethical. The drug won't be being tested for effect on pregnancy so the overall focus will be on non pregnancy stuff. Pregnancy may actually alter the effect of the drug so could render the whole trial void. Never mind possible effect on the fetus.

She sounds a bit thick.

And also it depends on the trial. I've been in a drug trial for over 5 years and there are definitely pregnant women in our fb chat group. Difference is I guess that we're all chronically ill so the benefits outweigh possible side effects though the Prof in charge says there's no increased risk in pregnancy.

If you had 1000 pregnant women in a trial, you would expect (sadly) quite a lot of miscarriages. As a researcher you might understand that they were within the expected range, they would have happened anyway. I think expecting a woman, who has just miscarried, to be able to see this in a pragmatic, blame free way, is unrealistic and cruel. They would blame the drug and they would blame themselves.

Occasionally a drug is found to be associated with a slight increase in risk, say heart attacks. Most people who had a heart attack on the drug would have had it anyway, but they still go to the papers and forums with their "I thought it was safe," stories. Nobody with a patent for a potentially useful drug is going to welcome that kind of publicity, one miscarriage story you can google is pretty much a guarantee pregnant women wouldn't take it anyway.

Also, a lot of medicines tested these days are for long term chronic conditions, so waiting 9 months to start on the meds, while your biology is all over the place anyway, isn't that bad.

We should include more women though, and more racial diversity. It would also be useful to trial co-morbidities like diabetes (as it's becoming common).

But then, once a drug passes, it's going to be out in the wild, and will inevitably end up being used on pregnant women (ie ones using it who then become pregnant)

No I don't think that's right. Generally drugs are not recommended in pregnancy. The only exception is vaccines.

So now I come back to the idea, that at a bare minimum, women becoming pregnant on the trial should stay in the trial - because the alternative is worse.

But you would weigh the risk for one pregnant person the clinicians knowingly expose to potential harm to the risk of unknown people who may take meds against recommendations on their own risk.

I do not think this is ethically appropriate.

It's a double-edged sword. There is some evidence that Metformin, used for diabetics, can help women with PCOS avoid early MMC. However, it would not be ethical to carry out trials so they don't happen. Some consultants are happy to prescribe Metformin to pregnant women, some aren't. There is no known risk but there does seem to be a general culture of avoiding giving pregnant or lactating women drugs, even if there is no evidence the drugs have negative effects.

I also had to fight hard to get prescribed thrush treatment both during pregnancy and whilst breastfeeding - Boots don't want to give anything to pregnant/breastfeeding women without a doctors prescription.

I think this person requires a history lesson about when experiments on pregnant women were done.

They are nothing more than an idiot who fails to have any level of understanding of ethics.

Cba to dignify it more than that.

I work in clinical trials these days. She isn’t correct on this - she is right that there isn’t much data on pregnancy and various drugs, but the exclusion of pregnant women is ethical.

Most trials require participants to take a pregnancy test at each visit. Some will require participants to be on two forms of contraception. We simply cannot take the risk of exposing a foetus to an unknown investigational product - it is NOT ethical.

The safety data for pregnancy comes from usage data. So a drug will end up on the market and inevitably women will become pregnant while taking it. The reports on those pregnancies form, in a way, an indirect safety dataset and form the basis of the pregnancy category system, along with animal studies.

It’s flawed, but I honestly cannot see any ethical way of making it better. You cannot test most (there are exceptions) drugs on pregnant women unless you meet extremely strict and stringent criteria.

Not all trials exclude pregnant women - but it’d be grossly irresponsible to allow women into a trial where the effects on a foetus are unknown.

It’s an incredibly difficult area. It seems so black and white - of course we shouldn’t experiment on unborn babies. But then you bump into reality - both that pregnant women get sick, and that sick women get pregnant. Some conditions only affect pregnancy - if they discovered something that was massively promising as a cure or preventive for pre-eclampsia for example, what do you do when you get to the human trial stage? Non-pregnant women or men don’t get pre-eclampsia (except for a small number of cases of post-partum pre-eclampsia). So who do you trial it on? Maybe you could ethically trial it on women who are already sick with the condition, and compare t with the standard of care. But what if it were a drug to prevent the condition developing? You’d have to trial it on women with no sign of the condition.

Similarly women who need medication for ongoing health issues get pregnant. What about their treatment? Should it be left to each individual pregnant woman to take the risks of continuing or stopping her regular drugs, with no evidence base or guidance and basically let every individual roll the dice for herself? Or should we attempt to apply the same safeguards and medical strictures that are available for everybody else by systematically applying drug trial standards to (consenting) women in these situations and then learn from them?

It’s incredibly murky and I don’t know what the perfect answer is, but a black and white “no trials when pregnant” is too absolute I think.

it's an interesting take.

but as pp describe there are trials in pregnant women. these are usually observational, i.e. they look at the effect of medicines that are taken during pregnancies.

if a clinical trial can take place and how it takes place is decided by ethics committees who have very strict frameworks on what can be done. and most importantly what shouldn't be done.

as a background: the nazis did extensive medical trials in concentration camps on scores of people. no consent sought. no ethical protocols followed (i.e. no pain relief for painful experimental procedures etc)

btw many off the shelf medications say 'do not take when pregnant' or 'speak to your dr/pharmacist' etc even though some of them are known (through observational trials over many years) to be quite safe for pregnant women and their fetus.

She's a "science journalist"? Then she should know that it's unethical to test most drugs on pregnant women.
As others have pointed out, the fetus is more sensitive to drugs than the woman carrying it, both because of the size difference and the fact that it's organs may not be developed enough to safely process the drug. And of course, the preganancy may be too short for the trial to give significant results.

Never in a month of Sunday's would you get it past ethics review. Unless the drug was thought to be treating a specific condition associated with pregnancy with a very clear benefit potential for the mother and fetus it's wildly unethical and violates Helsinki in soooo many ways....she's a twat.

www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/

Thalidomide. They don't dare.

So now I come back to the idea, that at a bare minimum, women becoming pregnant on the trial should stay in the trial - because the alternative is worse.

But if - as is likely- this number is too small to give the pregnant woman section of the study enough power to make the data meaningful, then it is a complete waste ie risk for zero benefit and therefore unethical. One of my areas is welfare and ethics review of medical experiments on animals (mice, mostly) and consideration of numbers is one of the first things on the project licence application to be considered. You can't use far more than you need...but the opposite is true too..you would not gain a licence if your project included too few for meaningful data to be collected- even for experiments in the "mild" category as it's just a complete waste of potential suffering.
You can (often must) do pilot studies on small numbers for new drugs or doses, but these are with a view to doing larger numbers within the same project as long as the pilots don't suffer side effects of unexpected severity. You can't just do a couple of pilots out of interest and leave it at that.