What’s a consumer to do?

You’ve no doubt been hearing the news reports about an analysis of clinical trials on the blood sugar drug, Avandia (rosiglitazone), finding an association with increased heart attacks and deaths. Consumers have become alarmed and caught in the middle of an inordinately fierce debate among various interests due to the obscene amounts of money — $3 billion in sales just last year — at stake.

The FDA issued a Safety Alert yesterday, advising diabetics talk with their doctors. Rather than panic, the public deserves to know and better understand what all of the fuss is about.

The research that began this recent furor was conducted by Dr. Steven Nissen, M.D. and Kathy Wolski, MPH, of the Cleveland Clinic. It was just published in the New England Journal of Medicine. They wrote that they were prompted to do this investigation because the drug had received FDA approval based on studies showing it could lower blood sugar (and glycated hemoglobin) levels. However, those studies had not examined if the drug actually reduced complications of diabetes, including cardiovascular events and deaths. Multiple (more than 50) other drugs that worked the same way (PPAR agonists) had failed to get FDA approval or make it to market because of excessive cardiovascular events during phase two and three trials, or their developments and marketing had been halted because toxicity had become evident, they said.

Doctors Nissen and Wolski were unable to obtain the original raw clinical data from officials of the drug company, GlaxoSmithKline; who refused to share it. So they had to rely on publicly-available data from the original information the company had submitted to the FDA. While they recognized the limitations of their meta-analysis, the pooled data from the clinical trial evidence showed a worrisome 64% higher risk for cardiovascular deaths and they felt it important to bring this to the attention of the medical community.

Adding to concerns, the Public Citizen issued a press release revealing the FDA knew of increased heart attacks among people on Avandia nearly five years ago but post-market safety concerns had not been addressed. An internal FDA memo dated July 16, 2002 said that based on FDA Adverse Events Reporting System, new cases of congestive heart failure were being reported among patients on these medications and “to an extent not clearly defined in the product labels.” Still, all of the facts on this issue are not yet available and caution is warranted until we do. A good overview of this situation for medical professionals, which includes a disclosure of some troubling evidence known by the drug company and thoughtful considerations of various suggestions, was written by Dr. Roy M. Poses, M.D. at Health Care Renewal.

So many of these types of problems could be avoided if doctors and those writing clinical guidelines would use higher quality standards for evidence, he said. How many times has the public been blindsided by learning years after a drug — for weight loss, cholesterol, anti-inflammatory, hormone or diabetes — has been on the market, that its dangers may exceed marketed benefits?

How many times have we heard “science says” something one day, and the opposite the next? Consumers, and many healthcare professionals, aren’t able to make it a full time job to review the medical literature and keep up with the controversies on every drug and therapy. Until medical and public regulatory professionals straighten themselves out, sadly the public is left on the short end of the stick.

Still, there are a few core concepts that can help you protect yourself and your loved ones. I have never known a study that was truly sound in the first place to ever be disproven; finessed and perfected over time perhaps, but never disproven. But plenty of bad ones are all the time.

So here are my top 12 down-and-dirty tips for how to know what to believe concerning medical research and how to recognize the real science.

1. Remember risk factors are not actual diseases, nor are they causes for diseases. If someone suggests a treatment for a risk factor or number — be it a body measurement like weight or blood pressure, or a lab test like blood sugar or cholesterol — rather than an actual disease, your radar should go up. Even more, if they suggest a number is a “pre-disease” of some type, run the other way!

As we’ve seen, extreme blood pressures and cholesterol levels may or may not be a symptom a disease, but changing them doesn’t cure the disease. Coarctation of the aorta can result in hypertension, but lowering blood pressure won’t cure the problem. Diabetes isn’t a disease of blood sugar levels, it’s a systemic metabolic dysfunction for which blood sugars are a rough measure and bringing blood sugars down doesn’t cure or prevent the disease.

2. Emerging science ... isn’t. Evidence to support the need for or effectiveness of a drug or treatment should be based on clinical intervention trials on actual people, not epidemiological correlations or suggestions from lab or animal studies. Suggestions, speculations, hypothesis, etc. are rarely convincing enough evidence for you to risk your life.

3. Clinical studies used as credible evidence should be done on people similar to you and should show a clear benefit in actual health outcomes — the most important one being reducing premature death — not simply change a risk factor number. False surrogate endpoints don’t count.

4. For trustworthy evidence, clinical trials should be long enough for sufficient problems to be identified and any true long-term benefits to be realized. Any weight loss intervention study under 5 years, for example, doesn’t even deserve a second glance. Remember, studies all weight loss interventions (diets to bariatrics) that show transient changes to surrogate endpoints, which always rebound, and to increase long-term health problems, do not make good evidence.

5. The well-designed clinical study ideally should be double-blind, randomized, the groups similar, and include a control group of people not taking the medication or treatment — not just a study pitting one drug against another. You also want to know that the treatment is better than nothing or a placebo. The study should be designed carefully to take into consideration obvious contributory factors and you should know what happened to everyone present at the beginning of the trial.

6. Avoid inappropriate generalizations or aggrandizements of the findings. If a clinical study shows a drug or intervention to be of some benefit as a treatment for sick people, remember, that does not mean that it has efficacy as a preventive therapy. Chemotherapy can be a lifesaving treatment for someone with cancer, but giving it to everyone to prevent cancer would not be good medicine.

7. The degree of benefit should outweigh the risks and side effects. Side effects reported among the select, idealized patients and settings used in the clinical trials for drug approval should be viewed as hints of what is likely a larger scenario in real life. People and situations are often more complicated than the single health problem addressed in a clinical trial.

8. Look at what the actual study shows and what the research data finds, because that can be very different from what an author may say or conclude, and most certainly different from the marketing and media hype. Beware the spin and bias.

9. The source of a study funding, impressive credentials of the authors, and prestige of the publication or institution do not mean that a study or clinical recommendation is automatically bad or good. Ad hominem attacks are the tactic of junk scientists and those unable to address the research evidence itself. It helps to learn to recognize sources that are repeatedly meticulous and careful; and those that repeat the same junk science tactics or repeatedly arrive at dubious conclusions.

10. What is being prescribed should have biological plausibility — and this can be a hard one to know without some understanding of biology, chemistry, toxicology, and physiology. That’s why embracing science and the scientific process is so important. Having a sense of history also helps because much junk science and popular myths are disproven and resurface generation after generation. Those myths do not deserve your attention. The maxim “if it sounds too good (or bad) to be true, it probably is” can be invaluable. “The dose makes the poison” is another proven adage that will stand you in good stead.

11. Remember, if it’s everywhere in the media, that’s marketing, not science. If research hasn’t been published, but is presented at a conference, on television or a media event, it isn’t anything to take seriously, either. Wait until it’s been published and you and scientists are able to scrutinize it.

12. Be a skeptic. Think critically and try to sort through the proof logically. Look at all sides and resist the temptation to jump on something because it sounds intuitively correct, it is popular and everyone else is doing it, or because you want to believe.

These won’t catch all the shenanigans, but they’re a good place to start and may help you keep safe and above the frey.

© 2007 Sandy Szwarc