Tuesday, February 15, 2005

Bleeding edge

I've always been a skeptic. Never one to believe in things that I couldn't see, touch, feel or smell, or things that simply didn't make sense right off the bat. By two, I had decided that Santa was clearly imaginary--that whole billion-presents-on-a-sleigh thing was obviously bogus--and wondered why my parents persisted in pretending otherwise. How gullible did they think I was? When I was old enough to start losing teeth, I simply handed my father the little bicuspid, bloody and wet, and left my hand out for the pre-ordained twenty-five-cent payout. No Tooth Fairy here; no Easter Bunny, no Great Pumpkin: an atheist from day one, no assembly required.

Starting in the mid-1970's, my very un-skeptical mother edited and published a bi-weekly newsletter "exploring the mind/body connection." It was filled with interesting but mostly unsubstantiated articles on how laughter could cure warts or hypnosis eliminate snoring, or the uncanny psychic abilities of parakeet owners. Mostly I thought the stories very silly, being my father's hard-nosed daughter, but as I was quite mercenary even at that tender age, I willingly coded return slips, stuffed envelopes and saved up my ill-gotten gains from the pockets of the starry-eyed subscribers--paid out by my parents in cans of diet soda, which I was allowed to convert to cash once the numbers reached undrinkable proportions.

There was one story that I did lock onto, however grudgingly, and which was repeated quite credibly in article after article over the newsletter's ten-year lifespan: the power of the placebo. If you believe something is going to work, it is more likely to do just that. If, as the story went, you believed you were getting acupuncture to relieve pain in your left elbow, it didn't matter whether the pins were placed correctly by a master acupuncturist or simply jabbed in randomly by an untrained research assistant: those who went in believing it would work for them had positive results, regardless of the "treatment". (How, exactly, does that belief or optimism trigger the physiological process of healing, or at least deliver some relief from the symptoms? I am fascinated.)


. . .


In the biopharmaceutical industry, clinical trials are usually conducted with multiple means of measuring efficacy. Patients, generally randomized into two groups sharing very similar characteristics of age, sex, stage of disease and treatment history, will be given either the active drug or a placebo. In so-called "double blind" trials, neither the patient nor the doctor knows who is receiving the real thing, and the coded tracking data is kept under strict wraps by the company or university managing the trial. In the end, various reports are made, the data is unlocked and analyzed from all angles, the FDA advisory panel reviews all the safety and efficacy data and makes its recommendation, and eventually the FDA bigwigs pronounce the official usefulness (or uselessness) of the drug.

Almost invariably, and even in studies of serious ailments, a statistically significant proportion of the placebo group reports an improvement in their symptoms (the placebo group almost always reports negative side-effects, also--a whole discussion unto itself--but at least they believe it's doing something). Doctors also frequently report seeing some improvement in patients whom they believe to be receiving the real drug but who are, in fact, getting nothing more than a cleverly disguised IV saline solution or sugar pill. Even the clinical investigators often find an improvement in the placebo group. So the effectiveness of the medication is necessarily based on comparison to placebo in what I think of as as the chemistry versus optimism showdown, and optimism usually has something good to say for itself.

So it seems that the power of belief, or optimism, or faith in medicine (I refuse to call it hope, as I'm still quite irritated with that word) can, in some people, bring about its own reward. But does it then follow that skepticism could bring about a negative outcome? And if that's the case, how exactly does a natural-born skeptic convert? Is it simply innate, and not to be learned? It truly feels like a hard-wired system for me.

My years in the biopharm industry instilled a lot of faith in the drug approval process, though clearly the ongoing safety monitoring program has left much to be desired and is now being revamped in the wake of recent extremely-rare-but-dreadful reactions to drugs like Vioxx or, a while back, Fen-Phen. I have been a carefully informed consumer of everything from ibuprofen and acetaminophen to generic-versus-name-brand thyroid replacement products, comparing side effects, interactions and clinical efficacy. So I was surprised, to say the least, when I found that neither Lupron nor the generic PIO concoctions are FDA approved for use in ART. And the Prometrium safety sheet specifically warns against its use in pregnant women. Not to mention the fact that the birth control pills I picked up today from a deeply puzzled pharmacist are most definitely not FDA approved for the suspended ovarian animation prior to an IVF cycle.

I realize that these products are part of standard ART protocols, and that, most likely, the only reason they're not FDA approved for such purposes is that the drugmakers don't want to finance additional trials proving their safety and efficacy in such a tiny market when they're already universally used in that setting, regardless. Once a drug's approved for sale, doctors can prescribe it for any condition they deem appropriate, and clearly they're appropriately prescribing these drugs in ART. But that doesn't keep me from wanting to see the data, to know the numbers--I'm left with a vaguely guinea-piggish feeling, though I know I'm in the good company of the tens of thousands who have gone before me.

Guess there's nothing left for it but to try to be optimistic that the drugs will work, that they won't harm me, and take it from there. It's a very, very small leap of faith, I realize, but I really don't have the legs for it. They're much better at walking, sedately and skeptically, from one known place to another.

9 Comments:

Anonymous Anonymous said...

You pose a lot of really good questions. I really hope being negetive or realistic as I call it isn't a bad thing for us. I am so not good at the whole optimism thing. Hoping for you, to hard to hope for myself.

I am a few days late, but I am so sorry about the negetive.

Sheri
Infertility Sucks

10:00 PM  
Blogger Emma Jane said...

I think Lupron had the weirdest package insert to read: prostate cancer and premature puberty seemed to be the primary on-label uses. Shiver.

It is utterly terrifying that none of this stuff has been objectively validated, in some sense. And that's part of why different clinics can do such different things--no one knows what's best.

But: how much would you demand to enroll in a double-blind study? Even if the answer is, "okay, don't charge me as much," that's still a big hit to an establishment that has no trouble recruiting paying customers. And there's no federal money for the research.

11:08 PM  
Blogger Orodemniades said...

Well, hell.

Maybe that explains why my Clinic doesn't proscribe BCP's for suppression...? They do use a cancer drug that can sterilize you instead, however.

hah hah.

Ah, Britain.

3:12 AM  
Blogger E. said...

I take Metformin for PCOS; I don't think it's approved for this use, either.

You raise an excellent point about placebos. Now I just have to figure out how to be positive instead of negative. Ha.

Does it help if we're hopeful FOR you this cycle?

5:24 AM  
Blogger Suz said...

I'm a couple days away from getting the drugs, so haven't had the chance to read the inserts yet, but know the sceptic feeling well already from when the ureologist prescribed my husband Clomid for sperm motility; definately off label here.

5:24 AM  
Anonymous Marivic said...

Thought-provoking questions (excellent, btw) aside, here's what I got from your post (also most excellent):

You regard "hope" as the inexplicably unsettling neighbor we try to avoid without being too obvious, and "faith" - the quiet neighbor you never really see but whose bumper stickers you admire, and whom somehow makes you feel good about your neighborhood.

You choose faith over hope, I find that fascinating.

I like your blog because it's funny yes but quite frankly, right now it's a wonking effort to find an infertility blog that doesn't have, well, a pregnant woman at the helm. It's marvelous and irksome at the same time (yes, I know I'm going to hell...) yet eased considerably by the writings of folks that are going through this stuff post-haste. Thanks for sharing, good luck with all this & that.

Marivic

9:26 AM  
Blogger Pamplemousse said...

As I prepare for first IVF, I too marvel at using a drug to deliberately put me into menopause! What if they can't get me out again, I ponder? What if I like it and don't want to leave old-lady land? Maybe it would be a relief???

9:44 AM  
Anonymous Day said...

I freak out when I think of all the drugs I've taken and injected to get and stay pregnant. I went through 10 ART cycles and a year before starting to try to conceive, was on Lupron for 10 months (ironically, not for infertility but to help manage my bone marrow disease which -ironic again- I likely contracted when I took the antibiotic sulfa).

The fact is, whatever unknown risks they may carry, these fertility drugs work. I never believed they would, but they did.

And they will for you, too...

...but I totally understand your uneasiness about it.

5:19 PM  
Blogger Wavery said...

You are so tuned in. And brilliant. I pledge my adoration eternally.

2:48 PM  

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