Mobe | The science of pharmaceutical research

The science of pharmaceutical research

Why it’s healthy to be a skeptic when evaluating treatment options

The wonders of modern medicine are endless. Proton beam therapy can blast brain tumor cells so precisely that a 13-year-old’s surrounding brain tissue is left undamaged. An aging hip can be replaced so an 80-year-old can walk again. Insulin helps a 35-year-old with diabetes keep her blood glucose under control.

But medicine isn’t perfect. And for every breakthrough that cures a disease (or makes it easier to live with one) there are many more treatments that only help a little. And there are many more that may have no effect or that may actually cause a particular person more harm than good.

So, it’s important to approach any decision that affects your health, or the health of someone you love, with eyes wide open.

Numbers can deceive

Let’s say a study has just been published about a new drug for a disease that runs in your family. It cuts your risk for that disease in half. Sounds like a drug you’d want your doctor to know about, right?

But what if you discovered the drug dropped your risk of developing the condition from 2 percent to 1 percent? Now imagine that the drug comes with harsh side effects. The decision of whether to take this new drug is no longer quite as clear.

This example gets at the heart of why it’s risky to base medical decisions on “relative risk” versus “absolute risk.” Yes, a drop from 2 percent to 1 percent is a 50 percent reduction (the relative risk). But the absolute risk (1 percent vs. 2 percent likelihood of developing the condition) can tell a much more helpful story when you are weighing whether this treatment is worth it.

Steve Woloshin and Lisa Schwartz, authors of Know Your Chances: Understanding Health Statistics, describe it this way: Knowing only the relative data is like having a 50 percent off coupon for selected items at a department store. But you don’t know if the coupon applies to a diamond necklace or a pack of gum. You know the value of your coupon when you know the “absolute” data.

Negative results may be hidden

It’s all about published results. Doctors depend on published clinical trials to help understand risk and guide medical decisions. But what if not all of the evidence gets published?

“Publication bias” happens when the outcome of a study affects whether or not it appears in a peer-reviewed journal. Negative results about a treatment or a drug are not as likely to make it to press as positive results. It’s human nature—and financial incentives. Fierce competition for funding and career promoting journal citations drives researchers to submit more studies with positive versus negative results, as journals are more likely to publish positive findings.

A study in the New England Journal of Medicine looked at 15 years of registered studies involving antidepressants—both published and unpublished—to measure the effect of publication bias.

The results were startling.

Among 74 studies, 37 of 38 studies with positive results were published, while only 3 studies with negative results were published. The remaining 33 studies either were either not published at all or were published in a way that conveyed a positive result.

Treatment decisions are therefore made based on partial information being available.

The risks of partial information can be tragic. In the 1980s, a drug called lorcainide was developed to prevent abnormal heart beats in people recovering from a heart attack. In trials of the drug, 10 of 50 patients who took it died. Only 1 person out of 50 in a comparison placebo group died.

The lorcainide study was never published, and pharmaceutical companies continued to develop similar antiarrhythmic drugs. Over the next 5 to 10 years more than 100,000 people died taking this class of drugs before the medical community realized what was happening.

Fortunately, there has been a growing movement to reduce publication bias due to the recognition of these negative consequences. Most clinical trials of drugs are now required to be registered on clinicaltrials.gov. The study sponsors are required to publish a basic set of results within one-year following the completion of the study—a first step in helping improve transparency of negative results.

Drugs and technology are newsworthy—behavioral health practices not so much

Ads for promising medications are everywhere. Take sleep aids for example: it’s hard to ignore the appeal of people slumbering soundly, then rising to a sunny morning, rested and refreshed.

However, did you know that the improvement offered by even the most effective sleeping pill is small? For every 13 people who take a sedative sleep aid, only 1 person has an improvement in their sleep quality. For those that see an improvement, on average they get an extra 25 min of sleep per night. On average, for every 6 people who take these sedatives, 1 person will experience side effects such as headaches, drowsiness, fatigue, nightmares, nausea, or gastrointestinal disturbances.

Cognitive behavioral therapy (CBT) for sleep on the other hand, one-on-one sessions with a professional psychologist, are not the stuff of magazine features or ad campaigns. This type of therapy treats the cause of sleep problems, does not have the side effect risk of a drug, and has been shown to be as effective as sedatives, while likely having a more long-term effect.

If physical activity (a.k.a. exercise) were a drug, it would be a blockbuster. There is evidence for exercise as a prescription for disease prevention and/or treatment for conditions such as heart disease, diabetes, rheumatoid arthritis, fibromyalgia, osteoporosis, cancer, depression, and more. In some cases, exercise can be as effective as pharmaceuticals, but without the uncomfortable side effects, yet we tend not to think of this powerful lifestyle intervention as “treatment.” For many of us, when life gets busy it can be easier to squeeze in a trip to the pharmacy than to get to the gym.

News organizations need headlines

As information consumers, our healthiest dose of skepticism should be reserved for the popular press—magazines, newspapers, and news sites. Writers and editors often seem to “spin” a story for maximum click-throughs. It’s important to be wary of red flags like these:

  • The story touts the “potential” of a certain treatment. This is often an indication that a treatment has only been tested on animals, a long way from being a viable option for humans. Stay tuned, but the most meaningful results may be many years away!
  • There’s a lack of data to back up a claim­—a good sign that there is none.
  • The headline is posed as a question, like this: “Can Facebook advertising prevent cancer?” The answer to that question is “no.” But such a framing lets the writer skirt accountability for sound reporting on an unproven (yet hard-to-ignore) claim.

The health journalism watchdog site healthnews.org has hundreds more tips, tools and reviews to help you become a smarter information consumer. And that’s something to aspire to. After all, your health depends on it.

Sources

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2. HealthNewsReview.org. Reporting the findings: Absolute vs relative risk. (N.D.) https://www.healthnewsreview.o...

3. Epstein, D. When evidence says no, but doctors say yes. Atlantic Monthly. Feb. 22, 2017. https://www.theatlantic.com/health/archive/2017/02/when-evidence-says-no-but-doctors-say-yes/517368/. Accessed March 30, 2018.

4. Turner, E. Et al. Selective publication of antidepressant trials and its influence on apparent efficacy. New England Journal of Medicine. 2008; 358:252-260. https://www.nejm.org/doi/full/...

5. Glass J, Lanctôt KL, Herrmann N, Sproule BA, Busto UE. Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits. BMJ. 2005;331(7526):1169.doi:10.1136/bmj.38623.768588.47. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1285093/

6. Mitchell MD, Gehrman P, Perlis M, Umscheid CA. Comparative effectiveness of cognitive behavioral therapy for insomnia: a systematic review. BMC Fam Pract. 2012;13:40. Published 2012 May 25. doi:10.1186/1471-2296-13-40

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8. Manson, J et. al. Estrogen plus progestin and the risk of coronary heart disease. New England Journal of Medicine. 2003; 349:523-534. https://www.nejm.org/doi/full/10.1056/nejmoa030808#t=article

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