A very disturbing article, the likes of which I’ve never read in all my years as a physician, appeared in a recent issue of the AMA’s Archives of Internal Medicine. Written by Neil Holtzman, MD, a Johns Hopkins-based pediatrician, it describes the circumstances surrounding the untimely death of his beloved wife of many years, Barbara Starfield, MD, also a Johns Hopkins physician whose specialty was public health.
Ironically, Dr. Starfield was nationally respected for her writing on the serious glitches in our health care system that would lead to her premature demise. Her two major concerns were:
- The impersonal over-specialization of the physician-patient relationship.
- A pharmaceutical industry that, to get approval for new drugs, palms off deeply flawed studies to the FDA while extolling a drug’s questionable “benefits” even as it underreports potentially lethal side effects.
That Dr. Starfield died from complications of the very issues she’d been warning everyone about underlies the sad irony of her husband’s article.
Dr. Starfield was in her healthy 70s when her drowned body was found in the family swimming pool. Because of the unexpected nature of her death, Dr. Holtzman requested an autopsy. The pathologist found that Dr. Starfield had died from massive bleeding into her brain, especially at a point where her head might have struck the side of the pool. However, there was also evidence of multiple small areas of bleeding throughout her brain with the appearance of small strokes. Adding further irony, just weeks before her death Dr. Starfield had written about her symptoms in her personal journal, wondering to herself if she might have experienced a small stroke, but later noting that she felt better the next day and had not pursued it further.
For the six months before her death, Dr. Starfield had been taking a medication called Plavix (clopidogrel), prescribed by her cardiologist after she’d had a stent inserted into a coronary artery to rectify coronary insufficiency (poor blood flow), which had been diagnosed three years earlier. Once a person has a stent inserted, the blocked artery is open and they can usually expect years of healthy life. Plavix, prescribed almost exclusively by cardiologists, acts like aspirin to reduce the ability of blood to clot. It’s generally agreed that using a medication like Plavix or aspirin to block coagulation (clotting) reduces the chance that a dangerous blood clot might develop in the coronary arteries and ultimately reduces the risk of a heart attack. Like many primary care physicians, I’ve never prescribed Plavix but do have several patients taking their cardiologist’s prescription daily.
When Plavix (which unsurprisingly is very expensive) was introduced years ago, the pharmaceutical company marketed it as safer than aspirin to prevent heart attacks, though this had never been proven. Looking back over the data that was submitted to the FDA, the evidence of any real benefit of Plavix over aspirin was actually very slim. The clinical trials submitted to the FDA had lasted just eight months, and yet the company described a drug that would confer “long-term benefits.” Although patients take Plavix for years, no study has ever shown any benefit of doing so. Despite what Dr. Holtzman later discovered was very iffy Plavix data, the FDA approved Plavix and cardiologists began routinely prescribing it, often for very long-term use (years), far longer than the drug had ever been studied. Interestingly, no one has ever conducted a simple study comparing Plavix to low-dose aspirin for heart attack prevention.
Dr. Starfield herself had written about the failure of adverse drug reactions to be systematically reported to the appropriate agencies. She was also concerned about the failure of this information to get into the hands of the very doctors prescribing the drugs. Both she and Dr. Holtzman had urged that drug companies face significant financial and criminal penalties when it’s discovered that a company has withheld follow-up information reported to them by both patients and physicians. Dr. Starfield emphasized that this withholding contributed to iatrogenic (physician-caused) death, now the third leading cause of death in the US. Obviously, getting information about adverse drug effects is a matter of life and, in Dr. Starfield’s case and likely that of others, death.
Plavix is the third most frequently implicated drug causing hospitalizations classified as “drug adverse events” in patients over 65. Once she was on Plavix, Dr. Starfield had noticed she was bruising more easily and bled longer following minor cuts. It’s possible that if her primary care physician, who’d known her for years, had been notified she was taking Plavix he might have recognized minor changes in her thinking processes that would have led to an MRI, which may in turn have picked up on the small hemorrhages in her brain. Dr. Holtzman reminds readers in his journal piece that his wife herself had written about the fragmentation and overspecialization of health care, with different doctors prescribing different medications and no single system in place to inform all doctors about a patient’s current drug regimen.
Exploring further the history of Plavix, Dr. Holtzman confirmed what his wife had written about the pharmaceutical industry for years. Of the six known large studies comparing Plavix to a placebo, the only two that showed clinical benefit had been funded by the drug’s manufacturer. The four other Plavix studies had received no funding from the industry whatsoever and not one showed clinical benefit of Plavix over placebo. Indeed, one of them actually showed the risks of Plavix exceeded its non-existent “benefits.” Even knowing this, the company had withheld this information from cardiologists and, after Dr. Starfield’s death, virtually none of the cardiologists surveyed by Dr. Holtzman were aware of this study.
The only journal offering a strong warning against Plavix was “Worst Pills, Best Pills.” Published by the not-for-profit Public Citizen, it has, over the years, influenced a lot of my own prescribing habits.
Dr. Holtzman concluded his piece by writing “specialization, fragmentation, drug orientation, and profit-seeking help make American medicine the most expensive in the world, but not the safest or most effective.”
Step-by-step to approved drug
I think the appearance of an article like this shows the medical profession is becoming seriously concerned that it has capitulated itself to the pharmaceutical industry. Here are the steps a new pill that you swallow or I prescribe has undergone:
- A pharmacologist discovers a molecule that, via lab animal testing, is thought might have an effect on the human body. Alternatively, the molecule of someone else’s successful drug is simply tweaked (hence the term “copycat drugs”).
- The molecule is sold to a pharmaceutical company, which patents it and agrees to pay royalties on it (unless the pharmacologist is an employee of the company).
- Based on additional research, the pharmaceutical company decides what the molecule might be useful for (this is easier if it’s a copycat drug). Success usually means suppressing the symptoms of a illness, although more recently hiring physicians to create a “new” condition by bundling some symptoms together (e.g., “social anxiety disorder”) is a preferred approach.
- The pharmaceutical company pays university-based physicians obscene amounts of money to conduct research studies using paid volunteers. Everyone in this food chain wants to please the pharmaceutical company, so researcher bias becomes the order of the day. The glowing “positive” results are sent to the FDA and the negative ones suppressed.
- Articles written by professional medical writers employed by the pharmaceutical company start appearing in medical journals.
- After FDA approval, more obscene amounts of money are spent promoting the drug to physicians and the public.
- By charging very high prices (which they justify to offset the “cost of research”), the pharmaceutical company garners enormous profits as long as the drug remains under patent protection.
- During these years when money is flowing in, the company suppresses negative reports that may be filed by doctors and patients or fails to act promptly on negative reports being received from the FDA.
- Finally, when the company’s patent expires, the trickle of negative reports turns to a gusher (because they’re no longer being suppressed) and there’s a trail of dead and wounded patients left in the drug’s wake. The same issue of Archives has a report on statin drug use in women being a significant cause of chronic fatigue—statins have been off patent for years.
My guess is that will take many years for this process to change. There are too many special interest groups involved and too much money at stake. The best way to avoid falling victim to the hungry maw of the pharmaceutical industry is to take excellent care of yourself (healthful diet, healthy weight, keeping physically fit, reducing stress) and to question the need for each and every drug your doctor wants to prescribe.
I recently traveled in Turkey and India. What I noticed in Turkey was that there was virtually no obesity, cigarettes have practically vanished, and the food at every restaurant was right-sized portions of a Mediterranean diet. Likewise Indians mostly were of a healthy weight and there were literally mountains of fresh fruit, veggies, whole grains, nuts, and seeds everywhere, all grown at local farms and sold or bartered at affordable prices. For health care, they’ll use blends of Ayurvedic herbs, homeopathy, and energy healing, resorting to Western pharmaceuticals only as a last resort.
David Edelberg, MD