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MDs distrust industry-funded studies

Posted by medconsumers on September 27, 2012

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©

Posted in Conflict of Interest, Doctors, Drugs | Tagged: , , , , , , , , , | 1 Comment »

Diabetes 2 drug warnings

Posted by medconsumers on September 23, 2012

Type 2 diabetes has reached epidemic proportions in the U.S., we are told. The high blood sugar levels that define this disorder are linked to a higher than normal risk of heart attack, stroke, and many nerve complications. Unfortunately, the drugs prescribed to lower this risk come with complications of their own. Aggressive lowering of blood sugar levels has severe, potentially fatal consequences. A recent study found that — of all medications—insulin and oral diabetes drugs are the second most common cause of emergency department visits and hospitalizations!

That the treatments for diabetes 2 might be worse than the disease has been an issue for years. click here  So has the possibility that the treatments are prescribed too intensively.  click here Then there’s the expanded definition diabetes 2 that, not surprisingly, had drug industry’s behind-the-scenes guidance. click here  Today’s post, however, deals solely with the potential overtreatment of people, aged 65 and older.  It is based on a new online first commentary in Archives of Internal Medicine.

A co-author David Aron, MD, Case Western Reserve University School of Medicine, Cleveland, explained in a telephone interview why a diagnosis of diabetes 2 in old age could be problematic:  “The benefits of better glycemic [blood sugar] control takes roughly up to about ten years to develop, so it’s only beneficial to someone who has a longer life expectancy.”  Put another way, the whole reason for diabetes 2 drug therapy is the lowering the diabetic’s increased risk for a long list of horrors including stroke, amputation, blindness, stroke, heart attack, and others.  But the rate of these complications does not begin to drop until the diabetic has been on drug therapy for about ten years.  Ever heard that before?

Intensive use of drugs to lower blood sugar levels is another problem for diabetics over age 65. The drugs prescribed for diabetes 2 range from metformin alone—thought to be the safest—to the riskier combination of insulin plus an oral drug class of medications called sulfonylurea. Age 65 is the point at which many people begin to develop other serious health problems that make them more likely to experience complications when the drug therapy causes the blood sugar to go down to dangerously low levels (hypoglycemia).  Dr. Aron’s commentary identifies a list of conditions that put older diabetics at risk for hypoglycemia.

Ominously, at the top of the list is: treatment with the combination of insulin plus a sulfonylurea drug (click here for brand names). The list also includes “chronic kidney disease, cognitive impairment or dementia, neurologic conditions that may hamper the ability to speak or respond to a hypoglycemic event, and conditions associated with weight loss, appetite disturbances, or altered medication metabolism.” Yet Dr. Aron has this caution, “I wouldn’t want concerns about hypoglycemia to be seen as a license to avoid appropriate treatment for diabetes 2.”

Now for the test result at which overtreatment and hypoglycemia complications become a possibility: The diagnosis of diabetes 2 is based primarily on the hemoglobin A1C test, which can also measure how well the treatment is working.  The A1C test shows the average blood sugar levels of the past three months. The A1C result is reported as a percentage. The higher the percentage, the higher a person’s blood glucose levels have been. For people without diabetes, a normal A1C level can range from 4.5 percent to 6 percent.

Dr. Aron and his co-author Leonard Pogach have identified 7 percent as the A1C level as significant for certain people with diabetes 2. Once the patient’s A1C level goes below 7 percent, they say, the potential for overtreatment kicks in for people over the age of 65 who are at high risk for hypoglycemia.  Their commentary is part of the “Less is More” series published regularly by Archives of Internal Medicine, a medical journal with the mission of addressing the problems of unnecessary medical care.

Alarmingly, Drs. Aron and Pogach describe the A1C test as not very accurate (no matter the age of the patient), “There is even greater inaccuracy in many point-of-care A1C tests,” they wrote, referring to blood tests administered in a doctor’s office, as opposed to a free-standing laboratory.

Dr. Aron was asked for more information about how people would know whether their test results could be trusted as the basis for long-term drug therapy “Yes, it’s scary,” he said. When pressed further,  “No test is 100% accurate,” he hedged, “And there is a National Standardization Project currently working on improvements (click here).”

Take-home messages:  Pay attention to your A1C test results and keep copies. If your A1C goes below 7%, talk with your doctor about lowering the dose.   Become an expert on diabetes 2, hypoglycemia and the controversies that dog both topics.  Learn more about the drugs you are taking.   Read the links within this post and “Related posts” below.

Non-pharmaceutical steps to take:  Improve your diet by eating real food, as opposed to fast or processed foods (read “Food Rules“).  Don’t forget regular aerobic exercise (read “You can be fat and fit“).  Do both and you might be able to avoid drugs.

Maryann Napoli, Center for Medical Consumers©

Related posts

Risks of diabetes 2 treatment  A meta-analysis of 13 randomized controlled trials  found that drug therapy does not reduce mortality and might, in fact, slightly increase mortality. Study participants were middle-aged and older.  Drug industry’s role in expanded definition of diabetes 2 is described, so there is reason to think that overdiagnosis explains part of the diabetes 2 “epidemic.”

Weight loss and diabetes 2   Former American Diabetes Association official takes issue with the organization’s standard advice about weight loss and the disturbing trend toward labeling people as prediabetics.

Posted in Chronic Conditions, Diabetes 2, Diet & Exercise, Drugs, exercise, Heart, heart disease, Type 2 Diabetes, unnecessary treatment | Tagged: , , , , , , , , , | 1 Comment »

Drugs for mild hypertension

Posted by medconsumers on August 18, 2012

Are you taking drugs for mild hypertension, yet you’ve not had a heart attack, stroke, or a diagnosis of heart disease?  A new review of all studies that followed people who fit this description could not find a benefit to drug treatment. Astounding — when you consider that half the people currently on blood pressure-lowering drugs have only mild hypertension. Not incidentally, the threshold for mild hypertension has been lowered considerably over the years, thus making more and more of us into drug customers.

The review was published this week by the Cochrane Collaboration, an international organization that evaluates medical research.  It’s the first hard look that any independent team of researchers has directed at the evidence for prescribing drug for mild hypertension.  The best of all available research boiled down to four clinical trials with a combined total of nearly 9,000 participants who had mild hypertension.  It should be noted here that these are old studies  …  from an era when mild hypertension was 140-159/ 90-99 mmHg.  All were randomly assigned to take a drug or a placebo every day for five years. While these four studies may be the best available, the reviewers found that they left a lot to be desired. Only one, for example, kept track of the number of participants who dropped out of the study due to adverse effects.

Here’s the Cochrane review conclusion:  “Available data from the limited number of available trials and participants showed no difference between treated and untreated individuals in heart attack, stroke, and death. About 9% of patients treated with drugs discontinued treatment due to adverse effects. Therefore, the benefits and harms of antihypertensive drug therapy in this population need to be investigated by further research.” The reviewers acknowledged that withdrawals may not be this high with today’s lower doses of thiazides and beta-blockers (two most common anti-hypertensive drug classes).

“We just assumed that there must be benefits to treating most people with mild hypertension and that the benefits were greater than the harms,” said James Wright, MD, co-author of the Cochrane review, referring to conventional medical wisdom.  In a telephone interview, Dr. Wright described his own reaction to what he and his co-authors found.  “It was shocking to me, and it changes the way I approach my patients with mild hypertension,” he said.  “I tell them that there is no proven benefit to continuing treatment.  Some say, ‘Fine I’ll go off the drugs.’  Others say, ‘I’ll stay on the drugs anyway.’”    What?  Some of your patients would actually stay on a drug after hearing that it provides no benefit! What about the unanswered questions about harm?   “For sure, there will be harm,” he responded.  “The idea that any drug is without serious adverse effects is just wrong.”

Dr. Wright, who is a professor of Medicine at the University of British Columbia, Vancouver, explained that the four trials in this review looked only for effectiveness and not serious adverse effects, and none were funded by drug companies.  Today, most drug trials are funded by industry, and all are now required to collect information about serious adverse effects.  Unfortunately, he said, many of these industry-funded clinical trials withhold findings that are unfavorable to their products. Too often, only some—-but not all—serious adverse effects are reported.

The conclusion of the Cochrane review calls into question the hypertension guideline recommendations in the US, Canada and Europe. These guideline groups have recommended treatment of all adults with a blood pressure of more than 140/90 mmHg, yet the reviewers found no proven benefit to treating people with blood pressures under 159/99.  The time is right for a rethink, as the reviewers observed, “The decision to treat people with mild hypertension  has important consequences for both the patients (e.g. adverse drug effects, lifetime of drug therapy, cost of treatment, etc.) and any third party payer (e.g. high cost of drugs, physician services, laboratory tests, etc.).”

More:

-Despite the title of the new Cochrane review —  “Benefits of drugs for mild hypertension are unclear” — all the study participants actually had what is considered to be moderate hypertension by today’s definition (140-159/90-99). If this describes you and you are currently taking anti-hypertenisve drugs, print out this abstract and discuss it with your doctor.  Disclosure: I am an unpaid contributor to the Cochrane Collaboration, which describes itself as “an international, independent, not-for-profit organisation of over 28,000 contributors from more than 100 countries, dedicated to making up-to-date, accurate information about the effects of health care readily available worldwide.”

-There are non-drug treatments for hypertension (e.g. diet, exercise, stress management, etc.). The Cochrane reviewers say that many people with mild hypertension might give them a try, if they knew the uncertainties of drug therapy.

-Dr. Wright is a co-author of an earlier Cochrane review that found no benefit for drug treatment that lowers blood pressure below 140/90. Read this 2009 interview with him.

-Here’s a 2009 post that presents a case for taking anti-hypertensive drugs whether or not you have high blood pressure. Small doses are key to minimizing adverse effects.  Learn your chances of having a stroke, heart attack or heart failure, as well as the drug treatment’s reduction of each.

– Read “Treatment guidelines and conflict of interest” which describes the drug industry connections of experts who set treatment standards.

-This is a trip-down-memory-lane historical post “Prehypertension—How real is this new “disease?” from 2003, when 120-139/80-89 was declared prehypertension.  This new information about the lack of proven benefit for treating mild hypertension makes the concept and treatment of prehypertension even more absurd.

Maryann Napoli, Center for Medical Consumers©

Posted in Alternative Medicine, Drugs, unnecessary treatment | Tagged: , , , , , , , , , , | Leave a Comment »

How prescription drug harms can go unnoticed

Posted by medconsumers on July 12, 2012

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?

Posted in Aspirin, Conflict of Interest, Doctors, Drugs, Heart, heart disease | Tagged: , , , , , , , , , | 4 Comments »

Time to rethink low-dose aspirin therapy?

Posted by medconsumers on June 20, 2012

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.

Posted in Diabetes 2, Doctors, Drugs, Heart, heart disease, hospitals, Men's Health, Type 2 Diabetes, unnecessary treatment, Women's Health | Tagged: , , , , , , , , , | 3 Comments »

Drugs to prevent heart problems

Posted by medconsumers on April 26, 2012

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

Posted in Alternative Medicine, breast cancer, Cancer, colon cancer, Doctors, Drugs, Heart, heart disease, Men's Health, Screening, statins, unnecessary treatment, Women's Health | Tagged: , , , , , , , , | 2 Comments »

The drug for memory loss

Posted by medconsumers on April 21, 2012

“Is it simple memory loss? … Or is it Alzheimer’s disease?” This was the headline—over the photo of a worried adult—for a pervasive drug ad of yore. It sent chills up the spines of many a middle-aged and older person.  Aricept, a drug for Alzheimer’s disease, quickly became a blockbuster in the U.S. to the tune of $2 billion in annual sales. All the more amazing, considering that Aricept is barely better than a placebo. Well before Aricept’s patent would expire, the company in charge of marketing had to come up with a plan for keeping profits high while fending off generic competition. Pfizer’s plan was simple—just increase the drug’s dosage.  Same useless drug, but a new improved dose!

The story of how Pfizer and Eisai, the company that developed Aricept, managed to pull this off was laid out in last month’s issue of the British Medical Journal.  I confess that when the co-author of this paper sent me a copy, I thought for a minute that I was reading satire (British publications have that effect on me). Somehow I had missed Aricept’s higher-dose ad campaign.

What makes this especially appalling and different from the usual ineffective-drug-makes-billions story, is this: Aricept is for people with a particularly devastating disease whose treatment decisions are usually made by the patient’s relatives who are often desperate for anything that might work.

Approved only months before Aricept was to lose its patent protection at the end of 2010, “The ‘new’ 23 mg product would become patent protected for three more years,” wrote Lisa M. Schwartz, MD, and Steven Woloshin, MD, both of the Center for Medicine and the Media at the Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, New Hampshire, with a long and impressive history of activism on the topic of misleading drug ads.  Why 23 mg?  Answer: Aricept is now available generically (donepezil), but only in 5 mg and 10 mg doses, and there’s no way these two doses can add up to 23.  Got it?

Initially, the U.S. Food and Drug Administration required the higher dose be proven superior to the 10 mg dose.  Eisai, Aricept’s manufacturer, agreed to the FDA’s demand that this be shown for both cognitive and overall functioning. The pre-approval trial of 1,400 patients barely showed improvement in the former and failed completely on the latter. Yet Aricept 23 mg received the FDA’s approval anyway.

Drawing from the FDA’s own publicly available documents, Drs. Schwartz and Woloshin found that Aricept 23 mg had been approved over the objections of the FDA’s medical and statistical reviewers. Russell Katz, director of the FDA’s Division of Neurology Products, who initially required the higher dose be proven superior on two measures, inexplicably, chose to reverse himself. “In my view, this strongly argues for a conclusion that the 23 mg does is very likely to also have an effect on overall functioning, despite this not having been demonstrated directly in this study…I believe that the sponsor has demonstrated that the 23 mg dose of Aricept is effective…I will approve this application.”

Russell Katz also went on record ignoring his own alarming assessment of the 1,400-person pre-approval trial: “There is a clear increase in the incidence of adverse events on the 23 mg dose compared to the 10 mg dose…These are not trivial events; in these patients, these could lead to significant morbidities and even increased mortality.”

All Pfizer and Eisai needed from then on was an immense marketing budget. Nurse educators were sent to the heavy-duty prescribers—neurologists at high-volume long-term care facilities. The sales pitch: “There are no ‘stable’ Alzheimer’s disease patients—therefore aggressive treatment is required.”

The Aricept 23 mg ads aimed at consumers relied primarily on visuals—shots of loving caregivers with a spouse or parent with Alzheimer’s disease and this implied message: Truly caring people would ask their doctors for Aricept 23 mg for their loved ones.  The ads say that the drug improves cognitive symptoms but not overall functioning, wrote Drs. Schwartz and Woloshin.  “But there is no explanation of why that matters.”  Side effects are mentioned without any information about how serious or frequent they can be.

The ad aimed at doctors is worse, according to Drs. Schwartz and Woloshin, because it contains “a stunningly erroneous statement in a large bold font: ‘Patients on Aricept 23 mg/day experienced important clinical benefit on both measures [cognitive and overall functioning]’.  “Worse, this statement is directly contradicted in smaller plain font that says ‘the results for global function did not show statistical significance’.”

Drs. Schwartz and Woloshin were shocked to find that this erroneous statement also appears on the Aricept’s label [the detailed information aimed at health professionals], “This study showed that patients on 23 mg per day experienced important clinical benefit on both cognitive and global measures (overall functioning).

Will the two companies get away with the deceptions? The stats are only just coming in. More than 68,000 prescriptions were written for Aricept 23 mg in the first six months after approval. The only bright spots in this saga are Drs. Schwartz and Woloshin, who have outdone themselves in exposing this particularly cruel drug industry deception. They have perfectly illustrated the M.O. for many big drug companies:  Why waste money developing a drug that actually works when profits can stay steadily high with one that doesn’t?

Maryann Napoli, Center for Medical Consumers©

Posted in Alzheimer's disease, Drug ads, Drugs | Tagged: , , , , | 1 Comment »

45 medical tests or treatments to avoid

Posted by medconsumers on April 11, 2012

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

Posted in breast cancer, Cancer, colon cancer, Doctors, Drugs, Heart, heart disease, heartburn, radiation exposure, Scans and X-rays, Screening, unnecessary treatment | Tagged: , , , , , , , | 2 Comments »

New Book: Mammography Screening—truth, lies and controversy

Posted by medconsumers on March 31, 2012

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.

Posted in Book Reviews, breast cancer, Cancer, Doctors, Drugs, radiation exposure, Scans and X-rays, Unnecessary tests, Women's Health | Tagged: , , , , , , , , | 6 Comments »

A new take on bone density retesting

Posted by medconsumers on January 19, 2012

Screening creates drug customers. Keep this little-known consumer beware maxim in mind when you read the new finding about bone density retesting.  Frequent screening bone scans, starting in early middle-age, have been the norm ever since osteoporosis was discovered in the 1980s. (Believe me, no one ever heard of osteoporosis before then, other than the few health professionals who cared for people of advanced old age.)  The new study shows that women whose first test at age 67 indicates normal bone density can safely delay having a second test for as long as 15 years.  There was a time, not so long ago, when women were advised to start bone density testing right after menopause. But then again, there was also a time when the diagnosis of osteoporosis was not made until a person suffered a fragility fracture.

Before I describe the new study, an historical context is in order. Merck, maker of the first osteoporosis drug, may also have been the first company to establish a winning “formula” for blockbuster drugs: 1) lower the cutoff point for the diagnosis of osteoporosis, better yet, fund a meeting in a beautiful place (like Italy) of high-profile osteoporosis researchers (aka, hired “consultants”) who will do it for you; 2) mount an “osteoporosis awareness” campaign to scare women into thinking the risk of hip fracture starts soon after menopause; 3) expand your market share with frequent mention of a new “disease” called osteopenia, a diagnosis that can be given to anyone who almost has osteoporosis; 4) encourage use of a new screening technology for identifying “at risk” women, and do it with an ad campaign that doesn’t mention your drug so it looks educational; 5) provide financial incentives to doctors who want to purchase screening equipment for their offices; 6) introduce your new drug Fosamax, which received FDA approval in 1995 and soon became a top-selling drug worldwide, despite its minimal effectiveness in reducing the chance of having a hip fracture (1%).  For more, read “The Marketing of Osteoporosis.”

Now for the study that appeared today in The New England Journal of Medicine. It followed nearly 5,000 women, 67 or older, with normal bone density at the hip and no history of hip or spinal fractures, or osteoporosis treatment. The research team led by Margaret L. Gourlay, MD, University of North Carolina, took off from the current advice that women should start having bone-density tests at age 65. This study was designed to determine how long it took for osteoporosis (defined as bone mineral density T score, −2.50 or lower) to develop in women with normal bone density or osteopenia.

The women were followed for 10 to 15 years. The findings were unexpected, according to Dr. Gourlay, who told the New York Times that she and her colleagues were surprised by how slowly osteoporosis progressed. Osteoporosis developed in fewer than 10% of the women who started the study with normal bone density and in fewer than 10% who had either “mild or moderate osteopenia.”  (And I was surprised that the New England Journal of Medicine would allow researchers to use the industry-created term osteopenia.) In summary, women with normal bone density or “mild osteopenia” at age 67 can safely delay having a second bone density test for 15 years.

I hope that word gets out to women about this study because it should cut back on the overuse of bone-density tests, as well as the overuse of Fosamax and other drugs in the same class called bisphosphonates (e.g., Boniva, Actonel, etc.). The test was initially portrayed to women and doctors as predictive of who is likely to suffer a hip fracture.  But Canadian consumer advocate Barbara Mintzes, University of British Columbia, had a more realistic take on this claim over ten years ago: “Bone mineral density testing is a poor predictor of future fractures, but an excellent predictor of start of drug use.” The overwhelming majority of hip fractures, by the way, occur after the age of 70.

Something to think about: Most medical research is now funded by industry, particularly the companies that make drugs, devices, and testing equipment. This study was funded by the U. S. National Institutes of Health.

For information about these serious adverse events associated with these drugs, read “Drugs for bone loss.”   And read this to learn why women should stop taking them after five years.  And here is Dr. Susan Love’s description of how bisphosphonate drugs work and why no one should be surprised that they are causing problems.

This post has been revised to reflect the following correction, added January 21, 2012.

The first version of this article, posted January 19, misstated the conclusion of this study.  The authors did not specify when women should be retested.  The original title of this post and the post itself have been changed accordingly.

Maryann Napoli, Center for Medical Consumers(c)

Posted in Drug ads, Drugs, osteoporosis, Screening, testing, Unnecessary tests, Women's Health | Tagged: , , , , , , , , , | Leave a Comment »