MDs distrust industry-funded studies

Here’s an interesting turn of events. A new survey shows that physicians will distrust the results of a study, once they see that it was funded by the pharmaceutical industry.  In fact, many physicians were more likely to trust research funded by a government agency like the National Institutes of Health. But here’s the twist: Many industry-funded studies are of very high quality and some taxpayer-funded studies can be of lesser quality.

If physicians’ prescribing decisions are not guided by the quality of the research, then we’re all in trouble.  But then again, maybe we’re all in trouble, anyway, given the fact that most drug studies are funded by industry. We already know that industry-funded trials tend to produce results that favor their products—and the studies that fail to do so never see the light of day. The latter problem has been resolved—somewhat— for new drugs.  Trials initiated after 2007 are mandated to register on a publicly accessible website so that everyone knows of their existence and goals.

But I digress. The surveyed physicians were given only the abstracts (summaries) of hypothetical clinical trials of three different drugs. The trials were of high, medium or low quality.  Each abstract disclosed whether the study had support from a pharmaceutical company, the National Institutes of Health, or made no mention of support. The follow-up questions determined physician understanding of the trials’ quality, their confidence in the results, and their willingness to prescribe the drugs.

“We found that respondents downgraded the credibility of industry- funded trials, as compared with the same trials randomly characterized as having NIH funding or having no source of support listed,” concluded Aaron S. Kesselheim, MD, Harvard Medical School, and colleagues who developed the survey, published recently in The New England Journal of Medicine.  Ironically, 75% of the surveyed physicians reported “accepting at least one type of industry support.”

What to make of all this?  I have to admit that I was somewhat surprised by the survey results. I didn’t think practicing physicians were that jaded, especially physicians who themselves take industry money. This survey is important, but there’s a far larger problem related to pharmaceutical industry funding. It was addressed by one memorable speaker at a conference held last year by the Cochrane Collaboration. “Many of the clinical trials conducted by the pharmaceutical industry are very well-designed, but they do not answer the questions we want answered,” said John Ionnaides, MD. “We want to know whether the new drug is safer and more effective than the older drugs,” he said.  The “we” he was describing are the physicians who prescribe the drugs as well as the people who take them.

Dr. Ionnaides, an internationally respected researcher, went on to explain that no drug company wants to risk a head-to-head comparison trial, which could find an older, cheaper off-patent drug is better than their new expensive drug. Instead, a new drug goes on the market having proven to the FDA’s satisfaction that it is better than nothing (a placebo). And that’s exactly the way the drug makers want it to be (and lobby Congress to make sure things go their way).

This research gap goes far beyond drugs. No head-to-head comparison study, for example, has been done to guide men through the thicket of treatment options for prostate cancer.

Perhaps information gaps like this can be tackled successfully by the comparative effectiveness research efforts that have emerged as a result of the Affordable Care Act. But wouldn’t it be better if taxpayers did not have pay for this important research? Isn’t it about time to take seriously an idea that bubbles up every now and then:  Make the drug and device companies contribute to a large research fund; and then make them step back to let independent researchers conduct the head-to-head comparison trials.

Maryann Napoli, Center for Medical Consumers©

How prescription drug harms can go unnoticed

Twelve years ago, the American public first heard the shocking news that deaths due to medical care constitute the third leading cause of death in the U.S.—after deaths from heart disease and cancer. Sadly, the death of the research physician who introduced this statistic has recently been attributed to her medical care. Implicated is the commonly prescribed and widely advertised drug Plavix.

The circumstances surrounding the death of Barbara Starfield, MD, of the John Hopkins School of Hygiene and Public Health, were described online first at the Archives of Internal Medicine. The story is told by her husband, also a physician, who has raised critical issues about how common but serious harms of prescription drugs can go unreported.  He calls on doctors and the general public to be vigilant about reporting adverse effects to FDA. His wife had published many papers about improving the quality of medical care.

Neil A. Holtzman,MD, got more information than usual because an autopsy was required for his wife. She died while swimming alone in a pool. Although the immediate cause of death was “pool drowning,” Dr. Holtzman wrote that he was stunned by the description of “cerebral hemorrhage” as the underlying condition. “The pathologist attributed the massive hemorrhage to cerebral amyloid angiopathy (CAA), listing “anticoagulation therapy” on the death certificate under “other significant conditions.” CAA is not so rare, says Dr. Holtzman who learned that it is present in about 8% of everyone over age 75, which includes his wife.

Plavix is the “anticoagulation therapy” mentioned in the autopsy report.  Dr. Holtzman explained that his wife had been diagnosed with a heart condition called coronary insufficiency three years before her death.  Initially, she was put on aspirin therapy, but six months later a stent was implanted to open the right main coronary artery.  Plavix is the standard open-ended treatment thereafter.

Unfortunately re the “thereafter” part, only two aspirin vs. Plavix clinical trials had been conducted in people who had stents implanted. (Not incidentally, both trials were industry-sponsored.) Neither lasted more than one year; yet many cardiologists prescribe Plavix beyond one year after stent placement, as did his wife’s cardiologist.

(Forgive me for inserting myself into this story, but my husband and I discovered the same gap in research information after he had a drug-coated stent implanted during a “possible heart attack.”   We too noticed the short duration of the two Plavix vs. aspirin trials.  And we were disturbed by the higher rate of major bleeding shown for Plavix plus aspirin compared to aspirin alone in one study of unstented people post-heart attack.  With his cardiologist’s approval, my husband stopped the Plavix  15 months after his stent was implanted and stayed on the 325 mg dose of aspirin. None of this bad news about Plavix was explained to us by the cardiologists, by the way, we found it on our own.)

Searching the medical literature for current Plavix data, Dr. Holtzman found two trials published after his wife’s death that showed a significant increase in major bleeds.  All but one of the Plavix studies were published before his wife died, but their alarming results seemed to be ignored by most cardiologists, he wrote. “Neither the American Heart Association nor the FDA issued an alert on prolonged use of the drug.”

Dr. Holzman observed that the studies on Plavix following coronary stent placement reflect the focus of the cardiologists who are largely concerned with the short-term effects of a drug following stent implants. The patient, on the other hand, would want to know about bleeding risks throughout entire duration of drug treatment.

The autopsy showed a bruise on Dr. Starfield’s scalp but no skull fractures. Her husband suspects that a bump against the bend in the side of the pool could have precipitated the cerebral hemorrhage. He knew that she had informed the cardiologist that she bruised more easily while taking Plavix and bled longer following minor cuts. Had cardiologists known to look for cerebral amyloid angiopathy, the “significant condition” listed on Dr. Starfield’s death certificate along with “anticoagulant therapy” perhaps a connection would have been made to the strokelike symptoms she experienced in her last weeks.

Ironically, Dr. Starfield’s death would not have been counted in the third leading cause of death statistic. When she identified the sources for this statistic back in 2000, she was careful to note that it is probably an undercount, given the fact that the studies looked only for iatrogenic deaths in hospitalized patients.  It doesn’t take into account people who die of medical treatment outside of a hospital.

Maryann Napoli, Center for Medical Consumers©

Related info: Report adverse drug reactions to the FDA’s Medwatch Program (for consumers) and (for health professionals).  Sign up for FDA drug alerts and recalls.  Read Dr. Starfield’s 2000 commentary in the July 26, 2000 issue of JAMA (Is US Health Really the Best in the World?).

Related post: Angioplasty overuse and Bill Clinton  2010 post about overuse of stents.

Stents vs drugs from one of our favorite websites.

Read this 2012 article by ProPublica Why can’t medicine fix simple mistakes?

Time to rethink low-dose aspirin therapy?

Here’s a new slant on the daily low-dose aspirin routine followed by millions of Americans: You might want to stop, if you don’t have heart disease or are at low risk for it. Why? The chance of having a rare but serious side effect from aspirin therapy may be higher than the chance of avoiding a heart attack or stroke.   And this goes for people with diabetes.

These new findings, published online first by the Journal of the American Medical Association, call into question the current thinking about the safety of low-dose aspirin therapy. They also brought to mind an interview I did years ago when doctors were telling us—in the media and in person—that statins are safer than aspirin. I was skeptical about the purported safety of statins because these cholesterol-lowering drugs were relatively new at the time. What’s more, the comparison didn’t seem convincing. After all, it took medical science a hundred years to understand the risks of aspirin.

But the research physician I was interviewing pointed out that all the aspirin vs. placebo clinical trials showed that—no matter how low the aspirin dose—there were always more cases of brain or gastrointestinal bleeding in the study participants on aspirin.

Naturally, I checked his contention and found that the smallest aspirin dose studied to date was a trial that included healthy postmenopausal women taking 100 mg aspirin every other day. And indeed, there were more cases of serious bleeding in the women on aspirin than in those on a placebo.

That’s my backstory  for the new evidence against low-dose daily aspirin use in people without heart disease. Surprisingly, a new study found that the incidence of major bleeding leading to hospitalization is much higher than has been reported in clinical trials. Significantly, this new finding is not based on people who took part in clinical trials.

The study was conducted in the Puglia region of Italy where researchers had access to the medical records of all its citizens. They singled out 186,425 people, aged 30 to 95 years, on low-dose aspirin therapy and matched them with an equal number of people of similar ages and health who were not on aspirin therapy. Both groups had equal number of diabetics (about 15%).  All were followed for nearly six years.

Here are the results: There were bleeding-related hospitalizations in 3,369 of the people not on aspirin therapy, and in 3,538 of those on aspirin therapy. Put another way, 169 more cases of serious bleeds in those on aspirin.

This study provides a more accurate, real-world assessment of aspirin therapy’s harm than a clinical trial because people who volunteer for research are typically younger and healthier than the general population. And those with multiple chronic conditions are usually excluded.

From the medical records of people hospitalized for severe bleeding incidents, the Italian researchers were able to identify those most likely to be affected. Men, for example, are more likely than women. So are people with previous hospital admissions for gastrointestinal problems, those on other drugs known to cause bleeding (e.g., Coumadin, Plavix), and everyone over age 70.

The editorial that accompanied this study made it clear that aspirin therapy’s benefit outweighs its harms for people with heart disease. “For 6 major vascular events [e.g., stroke, heart attack] prevented, approximately1 major bleeding event would occur; therefore, the value of aspirin for secondary prevention is not disputed.”   (Click here for another estimate)

As for everyone else—the people who don’t have heart disease—the Italian researchers described two noteworthy aspects of their findings:  It has long been known that people with diabetes have a increased risk (36%) of bleeding, but this is the first study to show that aspirin had no effect. Low-dose aspirin therapy neither decreased or increased the bleeding risk in diabetics.

The other important finding involves statins. (Yes, I’ve come full circle to statins and aspirin). About one-fourth of all people in this study were taking statins, which appeared to have a protective effect against aspirin, say the researchers, citing a “substantially lower risk of both gastrointestinal and intracranial hemorrhages associated with the use of statins.”  They cite several previous studies that confirmed this protective effect.

But things are not so clear for brain bleeds. The researchers cite a large, randomized trial published last year that suggested statins may increase the risk of intracranial hemorrhage [emphasis added].”The take-home message:  your risk of stroke or heart attack has to be high enough to warrant the newly identified higher risk of major bleeding. But you might need someone with an advanced degree in biostatsitics, rather than a family doctor, to help you sort things out.

To me, this is a cautionary tale relevant to all “preventive” medicines. If it took this long to understand aspirin, how long will it take to learn the full-story on the harms of newer drugs like Plavix and Fosamax that people are expected to take daily to cut their chances of heart attack or a fracture.

And keep this in mind: Aspirin therapy is for life, but this study (like most clinical trials) lasted less than six years.

Maryann Napoli, Center for Medical Consumers©

Related posts
Drugs to prevent heart problems
Low-dose aspirin and cancer prevention
Most drugs don’t work in most people  Read how doctors, journalists, and consumers are misled by the way drug-effectivess statistics are presented in medical journals.

Breast cancer and radiation

Want to know the best way to reduce your chances of developing breast cancer? Avoid inappropriate CT scans of the chest. This is the refreshingly blunt conclusion of a new study funded by the U.S. National Cancer Institute. The radiation exposure from this imaging procedure is huge,  the damage is cumulative, and the breast is known to be one of the most radiation-sensitive organs of the body. There has been an alarming five-fold increase in the use of CT scans over the last two decades.

CT scans of the chest are ordered for diagnosing diseases of the heart, the lungs, and even screening symptomless people for these diseases. And it is not yet clear whether the improvements in diagnostic accuracy outweigh the cancer-causing harm of radiation exposure.

Among the reasons given for the inappropriate use of CT scans are: financial incentives, especially for hospitals and physicians who own their CT equipment; expanding indications for appropriate use; fear of malpractice lawsuits; and public demand fostered by hospital advertising campaigns. Too often, radiation exposure is unnecessarily high due to poorly trained technicians, the lack of universally agreed-upon standards for minimal exposure, and failure to calibrate the scanning equipment to the size of the patient.

The National Cancer Institute-funded study was conducted by Rebecca Smith-Bindman, MD, a professor of radiology and biomedical imaging, epidemiology and biostatistics at University of California, San Francisco, and published yesterday online in the Journal of the American Medical Association (JAMA).  She has focused on the breast because of an Institute of Medicine report that was published at the end of last year. Commissioned by the high profile foundation called Susan G. Komen for the Cure, this report disappointed many breast cancer advocates who wanted to know which pesticides and toxic substance in consumer products are the most likely to cause breast cancer.

The Institute of Medicine found insufficient evidence for any of these potential health hazards, but singled out “avoidance of medical imaging as one of the most important and concrete steps that women can take to reduce their risk of breast cancer.” Dr. Smith-Bindman used the National Cancer Institute funding to document the rise in CT scanning between 1996 and 2010 based on the care of patients at six U.S. health plans with 1-2 million enrollees altogether. She found a tripling of the number of CT scans, and a doubling of per capita radiation dosage over the study period. It should be noted that this finding could understate the magnitude of the problem because physicians practicing in managed health plans do not have a financial incentive to overdo the ordering of tests.

Acknowledging the media attention given previous studies documenting CT scan overuse, Dr. Smith-Bindman noted in an online video provided by JAMA: “There is a belief that we’ve solved the problem about radiation dose due to increased awareness over the years, but I’m not convinced that we’ve gotten the doses down, particularly in children and young adults, which are much higher than I would like to see.”

People should ask for the radiation dose before agreeing to a CT scan and make sure the dose is listed in their medical records, she advises, hoping that a groundswell of consumers asking pointed questions will improve the current situation. “Many ordering physicians are insufficiently informed about radiation doses and the cancer risks attributable to medical images,   and yet this information is crucial to weigh risks and benefits and provide appropriate justification for the use of CT and other high-dose imaging studies to patients and families.” Testifying before Congress last week about radiation safety, Dr. Smith-Bindman reportedly said, “Some people have worried about the X-rays at our airports to screen passengers, but one CT scan is equal to approximately 200,000 airport screens.”

When this study was reported yesterday by Medpage, an information source for physicians and journalists, one of the first comments came from an anonymous expert who appears to be a medical physicist, which is a specialist in the health effects of radiation on the human body:

“One issue is the variation in image quality caused by differences in expertise and experience amongst equipment operators, maintenance and calibration protocols, and servicing intervals. Another is the variation in image quality caused by the use of older versus newer, mid-range versus high-end equipment. When I researched this area in some depth about ten years ago, I discovered that the top-end equipment was being built by Japanese firms and only being used in Japan. It simply wasn’t available in the USA, in the EU or elsewhere. I have yet to speak to a specialist in medical imaging technology, or a pathologist or oncologist, let alone a typical medical generalist, who has more than an entry level understanding of the medical physics employed in this area. Accurate images, taken from multiple angles, can be a real boon. But the average physician doesn’t know how to interpret them, and most radiologists refuse to discuss medical imaging results directly with patients.

And another comment from the same Medpage forum:

“For each non-emergency situation, ask your physician or dental  professional, ‘Is this imaging procedure going to change the  treatment plan?’  If they can’t provide an intelligent answer,  then I refuse or delay the test until I speak to someone who can.   Every time my <10 yr old child goes to the Orthodontist, the  assistant immediately says, ‘let’s get some x-rays’ (or even a whole  facial scan) and then gets mad when I question her.  They’ve never  actually recommended any treatment/action taken for my child’s  teeth; she is just being observed yearly so why take x-rays  additional to the ones she has at the regular Dentist?  On the  other hand, my ~40 yr old husband hit his head tubing in the  Smokies.  At the ER, I agreed on a head CT because having a brain  bleed, although highly unlikely, could be fatal.  So, each patient  needs to question the risk to benefit ratio and consider age at the  time of exposure.”

Maryann Napoli,Center for Medical Consumers(c)
Related posts:
Tests to avoid CT scans appear frequently on the specialists’ list of inappropriate tests.
CT scans: lots of radiation, little research Explains why CT Scan radiation dose is so much higher than that of a conventional x-ray. And how to determine when a scan may be inappropriate.
Another way to cut your risk of breast cancer:  Explains how mammography screening  increases your chances of  being  diagnosed with breast cancer and  treated unnecessarily for a cancer that did not need to be detected.

U.S. doctors’ income 2011

Physician income declined in general, although the top-earning specialties remained the same as in Medscape’s 2011 survey. In 2012, radiologists and orthopedic surgeons topped the list at $315,000, followed by cardiologists ($314,000), anesthesiologists ($309,000), and urologists ($309,000). Previously, radiologists and orthopedic surgeons led the pack, at a mean income of $350,000 each, followed by anesthesiologists and cardiologists (both at $325,000). The bottom-earning specialties in 2012’s survey were pediatrics, family medicine, and internal medicine ($156,000-$165,00).

Although decreased reimbursement has been the recent buzz-phrase, some specialties saw modest gains, whereas others saw significant declines. The biggest income increases were in ophthalmology (+9%), pediatrics (+5%), nephrology (+4%), rheumatology (+4%), and oncology (+4%). For declines, the largest were in general surgery (-12%), orthopedic surgery (-10%), radiology (-10%), and emergency medicine (-8%).

For employed physicians, compensation includes salary, bonus, and profit-sharing contributions. For partners, compensation includes earnings after tax-deductible business expenses but before income tax. Compensation excludes non-patient-related activities (eg, expert witness fees, speaking engagements, and product sales).

Average time spent with patients

As in Medscape’s 2011 survey, the 13- to 16-minute patient visit is still the most common, especially in the primary care specialties of family medicine and internal medicine. Anesthesiologists (49%), critical care physicians (44%), and neurologists (46%) spend more time with each patient: a mean of 25 minutes or more. A majority of dermatologists (40%), radiologists (8%), ophthalmologists (35%), and emergency physicians (35%) spend the least time — a mean of 9-12 minutes per encounter.

                                                                                  From the Medscape Physician Compensation Report: 2012 results.    Total respondents: 24,216 US physicians across 25 specialty areas

Drugs to prevent heart problems

Congratulations to the two cardiologists who went public with crucial information rarely explained to the public. Their target: Heart drugs prescribed to healthy people who are expected take them every day for the rest of their lives. Guess what? These drugs can be great at improving your blood test results but not so great at helping you live longer or delaying the symptoms of heart disease. (And isn’t that the point, after all?) Billions of dollars were spent annually on drugs that, initially, showed promise that didn’t hold up with long-term scientific scrutiny.  And too often, failure to prove any benefit does not dull the prescribing enthusiasm.

Vinay Prasad, MD, Northwestern University, Chicago, and Andrae Vandross, MD, Yale University, cite examples of widely prescribed drugs that were ultimately proven useless (Tricor),  dangerous (extended-release niacin), or their advantage is uncertain (Zetia, Vytorin).  In the current issue of Archives of Internal Medicine, the two cardiologists propose “setting the bar” higher for drugs prescribed to healthy people. This means clinical trials with a large number of healthy adults who are randomly assigned to take either the new drug or a placebo and are followed for many years. In other words, drug makers should prove their products can cut the rate of death, heart attack, stroke before the drugs are approved for healthy people.

As things stand now, drugs are usually approved after a few months of study on the basis of short-term results.  For example, a drug must be better than a placebo at lowering cholesterol, or blood pressure, etc.  It has long been assumed that this, in turn, will ultimately lower the rate of deaths from heart attack, stroke, etc.  This assumption hasn’t always panned out. This was shown in 2006, when a much-anticipated drug called torcetrapib was in the process of getting FDA approval for its ability to greatly increase the so-called good cholesterol. But the clinical trial had to be stopped because the drug also increased the number of deaths and heart problems.

Occasionally, the large clinical trial proposed by the two cardiologists is, in fact, conducted—-but the results aren’t in for a decade or two after the drug was approved.  Worse, prescriptions continue to rise for a drug found to be useless.  One widely prescribed drug called fenofibrate (some brand names: Tricor, Lipofen, Antara) was approved by the FDA in 1993 for the treatment of very high triglycerides in the blood. Tricor became a blockbuster four years after a 2005 meta-analysis cast doubt on the benefits of all drugs in this class known as fibrates. There were no improvements in overall survival, and this was confirmed in a landmark clinical trial. “Although it was prescribed for more than a decade to further improve lipid profiles [standard test for fats in the blood] for patients already prescribed a statin, we now know the error of this practice.”

Cost is no small matter, as noted in this paper. “Annual spending on statins exceeded $19 million in 2005, ezetimibe (in the form of Vytorin and Zetia) costs over $5 billion in 2007, and fenofibrate costs passed $1 billion in 2009.”

Another improvement suggested by Drs. Prasad and Vandross:  Drugs given to healthy people must be shown to lower the rate of deaths from all causes before they are approved.  Too often a drug will lower the rate of heart-related deaths but not the total rate of deaths. If the drug succeeds with the former but not the latter, this raises the possibility that the drug itself is killing some people.  The only way to rule this out is to demand that the clinical trials not only keep track of heart-related deaths but also total deaths.

If this sounds familiar, it is the same argument that has emerged over how to prove the lifesaving value of screening tests (also “prescribed” for healthy people). “While screening for breast, prostate, and colon cancer decreases cancer-specific death, none [emphasis added] have shown an overall mortality benefit in prospective trials,” wrote the two cardiologists.  Screening can lead to potentially fatal, unnecessary, aggressive cancer treatments.  click here for breast cancer screening,  here for prostate cancer screening, and here for colorectal cancer.

Whether these excellent proposals ever see the light of day remains to be seen.  After all, the current system of short-term pre-approval trials serves drug industry interests, and healthy people in early middle age are its favorite “market share.” (Unlike the sick and the elderly, healthy people have a longer lifespan ahead in which to take drugs.)  It’s a good idea to think long and hard before accepting “preventive” drug therapy if you don’t have heart disease.  Drs. Prasad and Vandross have given us the blueprint for the issues to be raised with the prescribing doctor.

Maryann Napoli, Center for Medical Consumers©

Related posts

Drug to prevent heart attacks and strokes

45 medical tests or treatments to avoid

Our medical care system has become a danger, an expensive, wasteful danger at that. So what else is new? You might ask. Now doctors themselves are recognizing the problem and going public with warnings, specifying tests and treatments to avoid under certain circumstances.  The primary care physicians led the way last year when they named the top ten “don’ts” in their field. Now nine specialty organizations have weighed in with their versions.  A momentous move, given the fact that these specialists are putting aside their own economic self-interest and warning their peers as well as the general public about the harm of overtesting and overtreatment.

Altogether 45 tests or treatments made the new list—five for each specialty. Yes, it’s about saving money; an estimated $660 billion is spent annually on unnecessary healthcare in U.S. And no, this is not about rationing; it’s about improving the quality of medical care and using it wisely.

The theme of this project, called Choosing Wisely, is this: Virtually all medical interventions entail some risks both large and small. An example of the former is the huge radiation dose delivered by CT scans; an example of the latter is the small chance of a puncture-related infection from a screening colonoscopy. And some tests that are risk-free can cause false-alarms that lead to more tests that are not. If you have nothing to gain from a test, why take even a small risk?

Here’s a “nothing to gain” example from the oncologists’ list: “Don’t perform PET, CT, and radionuclide bone scans in the staging of early prostate cancer or early breast cancer at low risk for metastasis.” Some reasons: “A lack of evidence to show these tests improve detection of metastatic disease or survival. Unnecessary imaging can lead to harm through unnecessary invasive procedures, overtreatment, unnecessary radiation exposure, and misdiagnosis.”

There’s also a recurring theme within the lists, namely, avoid imaging people without symptoms and people at low risk for the relevant disease. People in one or both of these categories run the risks but have nothing to gain in terms of improved outcomes. Examples: pre-operative chest x-rays, cardiac imaging stress testing for people without symptoms of heart disease.

Some lists warn against imaging even for people with symptoms, such as brain imaging for fainting or for uncomplicated headaches, because there’s no proof it improves outcomes. The cardiologists’ top five is all about inappropriate use of imaging with radionuclide and CT scans.

The strongest warning about reducing radiation exposure came from the American Society of Nuclear Cardiologists:  “Use methods to reduce radiation exposure in cardiac imaging, whenever possible, including not performing such tests when limited benefits are likely.” The word ‘methods’ also refers to calibrating the machinery to produce the best image with the lowest dose.

Sometimes a standard practice is just a waste of the patient’s time and money like this example from the allergists: “Don’t routinely do diagnostic testing in patients with chronic urticaria [hives]. Routine extensive testing is neither cost effective nor associated with improved clinical outcomes.”

Few treatments are addressed in this project, although one tops the gastroenterologists’ list.  It refers to the drugs like Prilosec and Nexium, which are widely prescribed for heartburn, gastroesophageal reflux disease, and gastric ulcers. The gastroenterologists’ advice: Use the lowest effective dose. (Click here for extensive information on this topic from Consumer Reports, which participates in Choosing Wisely.) The gastroenterologists also want their peers to restrain themselves on the repeat colonoscopies even for people who have had small polyps removed.

Another treatment example comes from the kidney specialists who are concerned about the overuse of a class of anti-anemia drugs.  “Don’t administer erythropoiesis-stimulating agents [Procrit, Aranesp, Epogen, and Eprex] to chronic kidney disease patients with hemoglobin levels greater than or equal to 10 g/dL without symptoms of anemia.” The kidney specialists could have taken a stronger stance with this example, given the fact that these drugs’ effectiveness is in doubt and they have killed an estimated half million people.  Click here for a Whistleblower’s Story.

Inform yourself

We consumers have a role in driving the market for unnecessary testing. Here’s the doctors’ side of the story: 30% of them admit that they order tests they know won’t help their patients but order them anyway because patients come in asking for them.  On the other hand, 80% of all medical care expenditures is driven by physicians.

Read more about Choosing Wisely, an initiative a foundation established by the American Board of Internal Medicine.  Click here for the names of specialty organizations and their respective lists.

Maryann Napoli, Center for Medical Consumers©
Related Posts
The primary care physicians’ list of 2011.
Heart screening tests
CT Scans: Lots of radation, little research

New Book: Mammography Screening—truth, lies and controversy

What happens when a popular cancer screening technology is found to be far more harmful than lifesaving? When the finding becomes clear decades after it was oversold to the public? When a lucrative industry, in terms of equipment, breast biopsies, drugs, etc., has already built around it that is now impossible to dismantle?

One might hope that science would win out. After all, mammography has the distinction of being a cancer screening test with extensive research behind it. In his new book Mammography Screening: Truth, Lies and Controversy (Radcliffe Publishing, London/New York: 2012), physician and research scientist, Peter C. Gøtzsche recounts what it was like to take a hard look at that research and find it didn’t match up with mammography’s sterling reputation.

The near-universal reaction? Shoot the messenger. Vicious attacks came from researchers, policymakers, and physicians. Too often aimed at the man himself rather than his critique. Opinions were fixed—mammography is risk-free and lifesaving. Anyone who disagrees publicly is causing deaths in women who might reconsider and stop having mammograms. The book describes the scientist’s 11-year investigation that uncovered mammography’s considerable harms, though they were “hiding” in plain sight—in the original studies that had long ago established mammography screening as a lifesaver.

Dr. Gøtzsche, director of The Nordic Cochrane Centre, Copenhagen, describes himself as someone who knew little about mammography when, in 1999, he was asked by the Danish Research Council to do an in-depth assessment of all mammography-related research. A statistician and expert in clinical trial design and analysis, Dr. Gøtzsche was the right man for the job. Denmark was considering a national screening program, but first wanted to know more. Bad signs were already showing up in Norway where such a program was underway. Screening decreased breast cancer deaths but, ominously, it hadn’t decreased the rate of deaths from all causes. Even more alarming, mammography failed to detect the most aggressive, deadly form of breast cancer.

Central to Dr. Gøtzsche’s conclusions are the nine randomized clinical trials that included a half million women altogether. The first took place in New York City, in the early 1960s; the last two trials were conducted in Canada and Sweden in the 1980s. “We were baffled by what we found,” he wrote. “We had expected them to be more convincing considering how popular mammography screening had become, despite its high cost.”

The results of these nine trials focused narrowly on mammography screening’s role in reducing breast cancer deaths. Dr. Gøtzsche may well be the first to step back and look at the big research picture, assessing the total death rate and the harm to women. His assessment for the Danish National Board of Health described the benefits as uncertain and raised the possibility that screening could cause more harm than good. It was ignored.

Dr. Gøtzsche continued mining the data from the nine trials and publishing frequently over the next decade. The first paper, co-authored with statistician Ole Olsen, appeared in 2000 in the British journal, The Lancet. But it was their second paper for The Lancet in 2001 that set off a furious international reaction. The nine mammography trials emphasize the number of breast cancer deaths among the participants, but Olsen and Gøtzsche contend that deaths from other causes must also be taken into consideration. These trials show that many more women given regular mammograms are treated for breast cancer than the unscreened women, and these treatments themselves may cause fatalities. Furthermore, overtreatment of ductal carcinoma in situ, often with mastectomy, was identified as “a considerable risk of mammography screening because most cases do not become invasive.” (Disclosure: I serve on The Nordic Cochrane Centre’s advisory board, am quoted in this book, and have reported Dr. Gøtzsche’s work ever since I first came across it in 2000.)

Reactions in the U.S. media were exceptionally virulent and prolonged. It was likely the first time that most physicians as well as the general public heard that some cancers will never cause death or symptoms. But this was not the first high-decibel mammography media controversy. In 1992, when the Canadian trial was published, it was roundly trashed because it came up with an unpopular finding: Mammography screening did not reduce breast cancer deaths, though it increased the number of cancers detected. Dr. Cornelia Baines, co-director of this trial, expected fellow scientists to take a dispassionate look at the finding to see why it differed from that of the earlier trials.  Instead, she became the target of numerous attempts to silence and discredit her.

When the mammography controversy surfaced again in the media in 2001, it was the policymakers, the radiologists, and the breast cancer specialists who came down hardest on Olsen and Gotzsche. To accept their conclusions would mean that hundreds of thousands of women worldwide have been treated for a type of breast cancer that would either regress or remain dormant. Who would “dig deep” into that possibility? Certainly not the doctors who for years have been sending their patients for mammograms. And certainly not the radiologists whose income had increased mightily—less from the screening test itself than from the money-making ancillary activities like stereotactic needle biopsies, continuing education courses, magnetic resonance imaging, and biopsy-related patents (click here for one example).

Most women don’t want to hear about mammography’s harms either. Fear of breast cancer sold them on mammography in the first place—without it, there would be no action to take. In the early 1970s when mammography screening was first introduced in the U.S., most American women were not particularly fearful of breast cancer, largely because it was seen as an old woman’s disease. But a multi-national cancer drug maker took care of that “problem” with annual breast cancer awareness campaigns featuring young breast cancer victims. The fear level is kept high for doctors, too, who are frequently reminded that “failure to diagnose breast cancer” is a leading cause of malpractice lawsuits.

Cancer charities take a well-deserved hit in this book for their refusal to admit that screening has a downside. Their misuse of statistics seems calculated to inflate the benefit of cancer screening. Consider the 30% reduction in deaths bandied about in the early years of mammography promotion. This statistic was downgraded recently to 15% by the U.S. Preventive Services Task Force. But both of these are relative risk statistics, which are typically misunderstood by doctors and consumers alike. Most relevant is the absolute effect of screening, not the relative effect, points out Gøtzsche who provides this explanation: “If 2,000 women are screened regularly for 10 years, 1 woman will avoid dying from breast cancer, and 10 healthy women who would not have been diagnosed without screening, will have breast cancer  diagnosed and be treated unnecessarily.”

At the end of last year, the Canadian Medical Association Journal invited Dr. Gøtzsche to write an editorial entitled, “Time to stop mammography screening?”  The Canandian Task Force on Preventive Health Care had just issued new guidelines,  stating that  “women who do not place a high value on a small reduction in breast cancer mortality, and who are concerned with false-positive results on mammography and overdiagnosis, may decline screening. ”  Dr. Gøtzsche describes this as “an important step in the right direction, away from the prevailing attitude that a woman who does not undergo screening is irresponsible.”

It’s hard to imagine that this could ever happen here in the U.S.

This book can serve as a guide to physicians and women who want to make their own informed decisions about mammograpy screening, who want an honest in-depth assessment of the research—one that should have given to the public before the introduction of mass screening. A similar “promote the test first, learn the harms later” story has unfolded recently about the PSA screening test for prostate cancer. You just might want to sharpen your critical skills and prepare in advance for the next cancer screening disaster.

Maryann Napoli, Center for Medical Consumers©

More about Dr. Gotzsche’s work:
Free mammography screening leaflet from the Nordic Cochrane Centre  It is also available  at The Nordic Cochrane Centre website in 13 languages.
Cut your risk of breast cancer—avoid screening mammograms. One-third of all breast cancers found on a mammogram are the forms of breast cancer that would never cause death or symptoms.
Breast cancer death rate has dropped, but not due to mammography  Improvements in breast cancer treatments are most likely cause. ‘Before and after’ studies conducted in countries that introduced mammography in the 1990s verify what was noticed in Norway in this era: Screening  does not detect the most deadly form of breast cancer; it has not reduced the occurrence of advanced cancers.
Poster for the 2002 Cochrane Colloquium  U.S. media coverage of the 2001 Lancet paper.

What MDs don’t know about cancer screening

Most primary care physicians are keen on cancer screening. In fact, sending symptom-free patients for regular tests is central to their practice. Yet an understanding of cancer screening statistics is critical to informed decision-making, whether you’re the doctor sending people for tests or a patient just following orders. A new survey of U.S. primary care physicians shows the majority accept misleading statistics as proof that screening works.

Four hundred and twelve physicians took the online survey, which was designed by an American and German research team with a history of trying to improve understanding of health statistics by health professionals as well as the general public. “Most physicians incorrectly equated improved survival and early detection as evidence of lives saved,” concluded the researchers led by Odette Wegwarth, PhD, Max Planck Institute for Human Development, Berlin, Germany. “Few correctly recognized that only reduced mortality in a randomized trial constitutes evidence of the benefit of screening.” The survey results were published this week in Annals of Internal Medicine.

The survey presented physicians with two ways of expressing the effect of a hypothetical screening test which was described as improved 5-year survival and increased early detection in one scenario and as decreased cancer mortality and increased incidence in the other. Though the type of cancer was not identified, the hypothetical test scenarios were based on real-life data from the European prostate-cancer screening randomized trial. And the 5-year survival statistics and the percentage of stage I prostate cancers came from the U.S. database of cancer statistics collected in 1975. To be safe, that year was chosen because it predates the introduction of any organized screening program for prostate cancer.

The physicians were more impressed with what the survey authors called “irrelevant evidence,” for example, a test with a large 5-year survival rate. Here’s why this is irrelevant: The older we get, the more cancers we have in our bodies; many will never become life-threatening. Prostate cancer, for example, is in the overwhelming majority of cases a slow-growing or non-progressive cancer.

Therefore, prostate cancer’s 5-year survival rate will look like a clear justification for early cancer detection because most men will die of something else. Conversely, they  could die six years after a diagnosis of prostate cancer and still be counted as a “survivor”. Furthermore, screening often moves up the time of diagnosis (and treatment) without moving back the time of death.  (By the way, we can thank the American Cancer Society for its long-time use of this extremely misleading measurement of a cancer screening test’s benefit. In the not-so-distant past, the ACS actually used the word ‘cure’ interchangeably with 5-year survival, thus making generations of cancer patients think that making it to five years meant something.)

Now for the other worrisome finding:  The surveyed physicians were less impressed with a test described as having “reduced mortality”. And they were more impressed with a test that finds lots of cancer. But screening for cancer will always increase the number of cancer cases diagnosed, compared with the number of cancers found in people who seek medical attention only after symptoms appear. That’s because screening detects many more cancers that do not progress, which falsely inflates the apparent benefit of a screening tests (a phenomenon that the survey authors describe as overdiagnosis). This is why careful researchers will—after many years of follow-up—-compare the overall death rate of both the screened and unscreened groups. It is the only way to sort out the people who actually achieved a life-saving benefit from those who were treated unnecessarily for a cancer they didn’t need to know about.

This comparison is also a way  for researchers to determine screening’s “cost” in terms of harms. Here’s what the European prostate cancer screening trial found:  For every one prostate cancer death avoided in the PSA screened men, 48 men suffered severe complications from unnecessary treatment of a non-progressive cancer.

What to do

If you are going for any cancer screening test, inform yourself first at the National Cancer Institute’s website.  And be sure to use the “health professional” version which is more honest and in-depth than the patient version. If you get most of your medical information from the media, plan on regular visits to this media fact-checking website (www.Healthnewsreview.org). See its recent excellent critique of the media’s take on the latest colon cancer screening research, particularly The New York Times’ erroneous portrayal of it as definitive proof for colonoscopy as the best screening method. Click here

Maryann Napoli, Center for Medical Consumers©

Related posts:
Most drug don’t work (This is about understanding drug trial statistics.)
PSA screening for prostate cancer
Cancers that do not kill
Reduce your risk of breast cancer: Avoid mammograms (unless you have a breast symptom)

Whistleblower’s story: New book reviewed

“Blood Feud: the man who blew the whistle on one of the deadliest prescription drugs ever” (NY: Dutton, 2011)  by Kathleen Sharp 

This is the true story of an expensive anti-anemia drug that came on the market for one purpose; was heavily promoted for several unproven uses; and how the drive for profits led two drug companies to commit fraud. Kathleen Sharp, a veteran investigative reporter, describes what happened from the perspective of a drug salesman whose company pressured him into achieving higher and higher sales targets. The drug maker provided a playbook of tactics known to manipulate physicians into writing more prescriptions and at higher, more dangerous, doses. Eventually, the drug salesman-turned-whistleblower comes to the horrifying conclusion that over a half a million people have died as a result of this drug. Its benefits, if any, remain unclear; its safety never established.  It is still on the market.

Central to the story is one of the first biotech drugs to go on the market. Erythropoietin is the man-made version of human erythropoietin, which is produced naturally in the body and stimulates the bone marrow to make red blood cells. Epo, as it is called, became known as a “blood booster,” sold by Amgen and Johnson & Johnson under the brand names: Procrit, Epogen, Aranesp, and Eprex (Europe).

Epo received FDA approval in 1989 to reduce cancer chemotherapy patients’ need for blood transfusions after it became known that the nation’s blood supply was infected with the HIV virus. In time, epo would be heavily promoted as an instant cure for chemotherapy-related fatigue and for anemia in kidney dialysis patients. (Disclosure: I am quoted in the book, speaking before the FDA Oncologic Drug Advisory Committee against J&J’s fraudulent direct-to-consumers advertising campaign for Procrit.)

The whistleblower ‘s story begins in 1992 when Mark Duxbury became a Procrit sales rep at J&J’s new biotech division, Ortho. Initially, Duxbury believed that he was selling an important quality-of-life enhancing drug for cancer patients suffering the debilitating effects of chemotherapy. Procrit, so he thought, would allow them to complete the treatment regimen.

The methods used by J&J to get its sales reps to turn Procrit into a blockbuster drug make for fascinating, though appalling, reading. Doctors were easily manipulated into prescribing more epo with rebates, secret discounts, honoraria, and other kickbacks.  In time, the entire Procrit sales force was encouraged by J&J to break the company’s own product license agreement with its partner Amgen. This agreement stipulated that J&J would stay away from the kidney dialysis market. (Amgen, maker of Aranesp, was the start-up company that did the original epo research.)

By 1993 Duxbury was a company award-winner for the greatest overall growth in sales in the western region of the U.S. He was rewarded with a higher income and an all expenses paid trip to a luxury resort. Still, J&J didn’t let up on the pressure to increase sales, making Duxbury conclude that the only way to meet his escalating quota was to “steal dialysis business”.

Doctors were encouraged to prescribe Procrit in high doses, particularly for cancer patients, because this would increase sales by hundreds of millions of dollars. That the deaths of about a dozen high-profile European cyclists were already linked to high dosing with epo (accessed via the black market) should have served as a warning.

This book is a goldmine of information about how the nation’s pharmaceutical companies inflate the cost of medicines while hiding the true cost from consumers as well as the government payers. What’s more, the drug makers in this story monitor doctors’ prescribing habits to determine the marketing strategies that work best; violate patient confidentiality laws by encouraging sales reps to troll medical records for the best drug-testing candidates; and use study participation to get doctors to prescribe epo for dangerous off-label purposes. Such tactics are not confined to the selling of epo.

Duxbury’s sterling career started to go downhill when he was deposed as a result of a lawsuit initiated by Amgen against J&J. (Depositions conducted over the course of several years serve as a major source for this book.) As a result, his own in-office memos revealed J&J’s orders to encroach on Amgen’s kidney dialysis territory.

Duxbury soon became a liability to his own company, which turned on him as if he were the one who thought up the illegal sales tactics.  He was fired in 1998. Many of the reps who had been instructed to sell Procrit for dialysis were also fired or resigned. Many would not learn—until years later—that their order to promote Procrit as an anti-anemia drug for kidney patients was an off-label use (unproven) use and thus a federal crime. (The FDA had approved Procrit to treat anemia only in cancer patients.)

The rest of the story involves Duxbury’s downward spiral— unemployment, lawsuits, depression, and self-destructive behavior—as he tried to alert the public about the dangers of epo.  The sinister way the Ortho division of J&J treated its own employee who, after all, was just following orders, should confirm your worst fears about corporate misbehavior. As Duxbury put it after his own lawsuit for wrongful termination turned up information new to him. “I was shocked to learn that everything I did at Ortho was illegal. They cheated not just the government but their own people too!”

Author Sharp says that the safety tests were never conducted for epo drugs, though such testing was required by the FDA contingent on approval. By the late 1980s, she states, “scientists knew that boosting red blood cells also thickened the blood, which increased the risk of clotting. Blood clots lead to strokes, heart attacks, and brain aneurisms.” What’s more, she writes, “No one could be sure that Procrit was safe at even recommended doses, according to several sources.”

In 2007 the FDA finally got around to protecting the public. The agency issued a warning about all epo drugs which by this time were also marketed for AIDS patients. New studies showed epo drugs associated with an increase in death, heart attack, stroke and tumor growth in subgroups of people with cancer and those with chronic kidney failure. Click here

Epo drugs continue to generate billions in annual revenues.  Duxbury’s whistleblower case is still making its way through the courts.

Maryann Napoli, Center for Medical Consumers©