Tuesday, July 29, 2008

Drug Companies Ignore Pregnant Women and Third World Countries

My favorite science journal, PLOS, has a nice series of articles on women's health and more specifically maternal health. PLOS, which I love because they are public access, is a top tier journal. The gist of the articles is that after the scariness of DES and thalidomide, maternal medicine development has been at a relative standstill. As pregnant women still often have the need for medication, this has de facto resulted in the off-label use of medication. According to Fisk and Atun, 75% of pregnant women are on at least one medication for which the safety has not been formally verified. This in no way means that all (or even any) of these drugs are actually dangerous--it moreso belies the fact that women are ignored by the drug companies. Only three new medications (atosiban, carboprost, and carbetocin) have come about in the last 20 years in the UK. This is in exception to abortifacients and reformulations. Moreover, two of them are only used post-delivery. The Big Medication Players in maternal health (magnesium sulfate, α-methyldopa, hydralazine, β-blockers, aspirin, and nifedipine) have all been around for decades.

Why is this so important? According to Fisk and Atun:
Worldwide, there are 536,000 maternal deaths annually, while nearly half the 13.5 million under-five child deaths occur as antepartum, intrapartum, or neonatal deaths.
In developing nations, the problems are even more pronounced because of their increased burden of disease. We do not know how to treat most tropical diseases in pregnant women, but that does not mean they are not getting sick and dying. I support careful testing of all people with no qualifications. Malaria, however, leads to a mortality rate of 50% in pregnant women in their 3rd trimester, according to White et al, and we do not know how to treat it. There is no easy answer. Clinical trials are difficult as it is, let alone one in pregnant women or in a third world country.

10 comments:

Habladora said...

Alright, I've got some questions:

What do you mean by "off-label use of medication" - I thought that off-label medications were just generic instead of 'brand name,' but equally tested. Is that wrong?

Do you mind linking DES and thalidomide to discussions of their scariness that you find valid?

What do you mean by "I support careful testing of all people with no qualifications"? Without restrictions? Tested for what?

Sorry to be so dense, but 2 out of our 4 contributors are non-scientists, and I'm one of them. So, you might have to back-track a bit for me.

Casmall said...

Another great post from Le Loup! Your post brings up so many issues its difficult to know where to start. Is this primarily an issue of drug companies not having the incentive to service the poor, or is it calculated risk aversion towards testing drugs in pregnant women? Both?
By the way, this is a great example of the failure of magic market forces to provide solutions.

Renee said...

It is my understanding that Malaria is a preventable disease, perhaps we should start there rather than looking for a pharmaceutical solution.

Le Loup-garou said...

Off label use of a medication is when it is used for a purpose that has not be officially tested. For example, gabapentin (Neurontin) is very effective drug for the painful tingling of the feet in diabetics. This is called peripheral neuropathy. It has not been tested officially, but it is well known to work. Off-label use is typically accepted by experts in the field and should not be considered renegade medical practice.

Le Loup-garou said...

DES (diethylstilboestrol) is a synthetic estrogen, which when given during pregnancy to encourage continues pregnancy, caused clear cell adenocarcinoma of the vagina and cervix in the offspring. This was first shown in 1971.

Thalidomide was marketed as anti-insomnia and anti-anxiety medication for pregnant women in the 1950's and 60's. It was shown to be a potent mutating agent in fetuses, causing malformed limbs. Interestingly, it has been shown to be a great alternative treatment for multiple myeloma.

What I meant by 'no qualifications' is that clinical trials should always be safe for the patient. There should be no exceptions to this. The stated purpose of clinical trials, however, is clearly stated to answer a specific scientific question, NOT to help the individual, who may or may not benefit from the trial.

Sorry I was so unclear before. That's what I get for dashing out a quick post...

Habladora said...

Oh, thanks for answering my questions! I'd say I feel 10% smarter now!

Le Loup-garou said...

Casmall: I think it is a little bit of everything. There is a justified apprehension of the drug companies to test pregnant women and a lack of financial rewards for treating the third world. Although the PLOS articles focused on pregnant women, there is a general disregard of both women and children by the pharmaceutical industry. These groups are historically poorer, more disenfranchised, and have poor lobbying power.

Another Anonymous Poster said...

Renee-

I don't know that I would consider malaria to be a 'preventable' disease. Nets might work to some extent, but they can only cover so much, can develop holes/open points, and appear to have some cultural issues in some locations that inhibit acceptance.

(side note: they apparently resemble the funerary veils used to cover the dead in some sub-Saharan cultures, so people don't want to cover their beds/cribs with something that makes them look like the occupant is dead. I guess there's not much of a goth/vampire subculture in those parts that might find that cool)

Anyway, the only other method of prevention that I know of would be insecticide spraying. The goal there would be to kill the mosquitoes that carry the plasmodium that causes the disease. We tried that, but 1). the insects become resistant to the agents, 2). the agents kill off all sorts of beneficial insects, and 3). the agents have all sorts of other effects on other animals. "Silent Spring" documents this pretty well.

Plus, it seems to be a fine line between spraying insecticide and using pharmaceuticals.

That just leaves anti-malarial drugs, and the plasmodia become resistant to them all the time.

daedalus2u said...

I think the examples that the pharmaceutical industry is looking at are Bendectin and silicone. There was no evidence that Bendectin caused birth defects, but that didn’t stop the manufacturer from being sued and from awards being made. Every good study of silicone has shown it to be safe but that didn’t stop Dow Corning from being put out of business.

There is similar stuff going on with vaccines. The “vaccines cause autism” controversy is manufactured by lawyers trying to win the legal lottery.

There is such a degree of difficulty in developing any type of new treatment. It is much more difficult than I thought when I started working on my nitric oxide stuff.

Le Loup-garou said...

daedalus2u, you make some great points. I think that we may have crossed the line between patient protection and litigiousness.