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December 05, 2008

Making Use of Comparative Effectiveness Research

Maggie Mahar

This post was written by Maggie Mahar and Niko Karvounis

Last week the New York Times published a story about one of the biggest medical trials ever organized by the federal government,  a study that showed that the newest, most expensive drugs used to treat high blood pressure (a.k.a. hypertension) work no better than inexpensive diuretics—water pills that flush excess fluid and salt from the body. Moreover, the research revealed that the pricier drugs increase the risk of heart failure and stroke. 

The trial was completed in 2002. Why is the story running now? Because six years later, the findings still have had little impact on what doctors prescribe for patients suffering from hypertension.

Allhat –which stands for the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial—demonstrated that when, it comes to preventing heart attacks, the diuretics—which have been used since the 1950s and cost only pennies a day—is just as effective as newer calcium channel blockers and ACE inhibitors that cost up to 20 times as  much.

And the diuretic is safer. Patients receiving Pfizer’s calcium channel blocker (Norvasc) had a 38 percent greater chance of heart failure than those on the diuretic. And those receiving AstraZeneca’s ACE inhibitor were exposed to a 15 percent higher risk of strokes and a 19 percent higher risk of heart failure.
Meanwhile, NYT reporter Andrew Pollack noted, the diuretics cost only about $25 a year, compared with $250 for an ACE inhibitor and $500 for a calcium channel blocker.

In a rational world, the results “should have more than doubled” use of the less expensive drugs, says Dr. Curt D. Furberg, a public health sciences professor at Wake Forest University and the former head of the Allhat steering committee.

But that didn’t happen.  Instead the share of hypertension patients receiving a diuretic rose only slightly: from 30 to 35 percent before the results were announced, to roughly 40 percent a year later. Since then, diuretic sales have leveled off, and the Times reports, and “use of newer hypertension drugs has grown faster than the use of diuretics.”

Big Pharma Pushes Back

Why did the 42,000 patient, six-year, $100 million clinical trial have such a small impact? Furberg blames the drug industry.

Consider how Pfizer reacted when Cardura, a fourth drug that went head-to-head with diuretics in the Allhat trials, failed the test. Over the course of the study, Furberg & Co. discovered that “patients taking Cardura faced serious risks: they were almost twice as likely as those receiving the diuretic to require hospitalization for heart failure.” Alarmed that putting patients on Cardura would mean putting them in danger, the Allhat team stopped testing Cardura in 2000, shortly before the study formally ended. 

Cardura’s manufacturer, Pfizer, was quick to move when it heard the bad buzz surrounding its product. “Rather than warn doctors that Cardura might not be suited for hypertension,” says the Times¸ “Pfizer circulated a memo to its sales representatives suggesting scripted responses they could use to reassure doctors that Cardura was safe…” The company also mobilized its sales staff to downplay Allhat’s findings: “[I]n an e-mail message unearthed in…court documents, a Pfizer sales executive boasted to colleagues that company employees had diverted some European doctors attending an American cardiology conference from hearing a presentation on the Allhat results and Cardura. ‘The good news,’ the message said, ‘is that they were quite brilliant in sending their key physicians to sightsee rather than hear Curt Furberg slam Pfizer once again!’”

But Furberg did knock Cardura again in a 2004 article in which he accused the company of treating the trial results “as a marketing problem rather than a public health issue.” He noted that the company never submitted the Allhat results to the FDA, nor did it make an effort to inform doctors and patients of the risks associated with Cardura.

Meanwhile, Pfizer touted its other entry in the blood-pressure medication bake-off, Norvasc, the calcium channel blocker. By 2002 Norvasc was the best-selling hypertension treatment in the world, with sales of $3.8 billion, and Pfizer’s second-biggest drug behind the cholesterol medication Lipitor.

The company beat the drum for Norvasc. In a news release after the Allhat results were announced, it claimed that Norvasc was found to be “comparable to the diuretic in treating fatal coronary heart disease, heart attacks and stroke.” And, the Times reports, “in a medical journal advertisement, it proclaimed ‘ALL HATs off’ to its drug.

Neither the news release nor the ad included the 38 percent greater risk of heart failure with Norvasc that Allhat exposed.

Pfizer CEO Hank McKinnell was emphatic in his support for the drug “Contrary to what you might have read in the press,” Mr. McKinnell said, “Allhat is extremely positive for Norvasc. It will be our job to explain that to the medical community.”

And Pfizer did just that.  By 2006 sales had hit $4.9 billion—up from $3.8 billion in 2002.  That year, Mayoclinic.com advised patients: “A large group of medical experts known as the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends that most people should try thiazide diuretics as the first choice to treat high blood pressure and heart problems related to high blood pressure. But Big Pharma’s money talked louder.

Meanwhile, critics emerged—as they always will—to question the design of the Allhat trial. And a smaller, less definitive Australian study declared an ACE inhibitor superior to a diuretic. This all muddied the waters.

But the hundreds of millions that drug-makers spent promoting their more expensive products made the difference. No one was making a huge profit on diuretics, so no one was spreading money around to market them.

What the Allhat Story Means for Health Care Reform

If you are a health care reformer, you might find this story discouraging.  Certainly, when the American Prospect’s Ezra Klein reported on it, he sounded glum:  “Folks looking to things like comparative effectiveness review to save the health care system should take the story seriously. Evidence is only effective if physicians use it. And right now, they have no real reason to use it.

“Even in a system this expensive,” Klein noted, “there's no internal incentives to aggressively cut costs. Maybe it's time there were.”

Klein then suggests that doctors should be paid “by capitation—if they got a fixed amount of money per patient, and they kept whatever they didn't use…it’s hard to imagine that they wouldn’t have been more interested in the study’s results."

It’s not clear how capitated payment would motivate doctors to prescribe a cheaper, equally effective drug since it’s the patient (or his insurer), not the doctor, who pays for the more expensive drug. Though one could argue that if doctors were paid a lump sum to keep patients well, they would avoid a riskier product.

But on the main point, Klein is right.  Data alone won’t cut it. Someone with clout is going to have to turn comparative effectiveness research into health care policy.

Here we come to the good news: the U.S. is now poised to give evidence-based medicine the institutional backing that the Allhat research lacked. That is why the Times ran the story last week. Three years ago, there was no hope that research like this would translate into policies that motivate doctors to practice evidence-based medicine, and so little reason to lament how little effect the Allhat research had. Now there is.

Legislation Already In Congress

Both President-elect Obama’s health care plan and the proposal for reform outlined by Senator Finance chairman Max Baucus paper call for a  public Comparative-Effectiveness Institute. Former Senate Majority Leader Tom Daschle, who will be the next Secretary of the Dept. of Health and Human Services,  and the point man on the transition team’s working group on healthcare, has talked about the need for such research to set guidelines for federal medical programs.

Moreover, last summer, Baucus and Senate Budget Committee chair Kent Conrad in August introduced a bill (S 3408) to create a comparative effectiveness institute, which would function as a not-for-profit private entity, not a federal agency. This would insulate it, at least to some degree, from Congress and the lobbyists who woo our legislators.

At the time, Congressional Budget Office Director Peter Orszag estimated that the U.S. could save up to $700 billion annually in health spending by identifying treatments that do not produce the best medical outcomes. Orszag’s support is key: since then, President-elect Obama has appointed him director of the Office of Management and Budget (OMB). Widely respected, Orszag is likely to become a powerful figure in the new administration.

Baucus has  explained that the Health Care Comparative Effectiveness Research Institute would be "responsible for setting national priorities" for head-to-head trials and would contract with the NIH, the Agency for Healthcare Research and Quality and private entities to provide peer-reviewed research studies that "answer the most pressing questions about what works in health care.”

According to the Kaiser Daily Health Policy Report, the Institute’s budget would be small to start—just $5 million in fiscal year 2009—but would climb quickly to $300 million in FY 2013. It would be funded by the federal treasury, Medicare and private insurers. Both Karen Ignagni, president of America’s Health Insurance Plans (AHIP), and BlueCross and BlueShield Association President Scott Serota  announced support for the plan. (As well they should—the institute could save them billions of dollars by exposing ineffective treatments.)

But here’s the tantalizing part of the proposal. According to Kaiser “The Institute would be governed by a public-private Board of Governors. The 21 members of the Board would include the secretary of HHS and the directors of AHRQ and NIH. The Board's other 18 members, to be appointed by the Comptroller General, would include representatives from three of the following entities: private payers; pharmaceutical, device and technology companies; patients and health care consumers; physicians; and agencies administering public health programs.”

As HealthBeat observed at the time, “[There appear to be five entities and] it seems that the 18 board members will be drawn from three of them.” Who will be left out?  To HealthBeat, the answer seems obvious:  pharmaceutical, device and technology companies should not have a seat at the table. Their financial self-interest (which would lead them to favor the most expensive products) creates an immediate conflict of interest. They should be consulted; but they should not have a vote.

We’ll see what happens. No doubt, the bill will change many times as it wends its way through Congress. But the president-elect, Orszag, Daschle and Baucus all recognize that we must wring the waste out of our health care system.

Research is Available

Skeptics suggest that even if the new administration creates a Comparative Effectiveness Institute, it will be a long time before it generates enough research to make a difference.  But this just isn’t true. The Institute does not have to re-invent the wheel.

We already have comparative studies like the Allhat trial plus work done by the U.S. Agency for Healthcare Research and Quality. Many studies have been done in Europe, where governments regularly use such research to make coverage decisions.   As the Times reported recently, “Membership in an international group of drug and device assessment agencies has grown to 45 from 8 in 1992.”

In addition, the Veterans’ Administration, Kaiser Permanente and the Mayo Clinic all have electronic databases showing how patients fitting a particular profile have reacted to various treatments. This observational data can be very useful.

Moreover, as Osrzag’s Congressional Budget Office pointed out in December of 2007, we’ve already  seen comparative effectiveness studies on a wide range of treatments, pitting angioplasties against drug regimens for heart patients, gauging the effectiveness of surgery for patients with emphysema, testing statins, and weighing mammograms against the combination therapy of mammograms and MRIs for breast cancer. Yet for all this research, our health care system remains bloated, inefficient and wasteful. In other words, Allhat isn’t the first time that good research has failed to change the game.

Part of this is because a for-profit health care industry opposes any efforts to reduce waste. One man’s risky and over-priced treatment is another man’s income stream. But the other problem is that our health care system doesn’t have a mechanism to do anything with good research except to let people talk about it informally

TCF’s Working Group on Medicare Reform

The Century Foundation’s Working Group on Medicare Reform already has discussed how Medicare might integrate the Institute’s comparative effectiveness research into its coverage decisions. The Group recognizes that Medicare would be reluctant to simply refuse to cover a popular, widely used treatment—even if there were evidence that it was riskier as well as more expensive than an equally effective alternative. Politically, that is probably a non-starter.

Nor is it likely that Medicare will refuse to cover treatments on cost alone. This would mean putting a price on what a year of life is worth when deciding whether to cover a drug that would give a cancer patient an extra year. The TCF Working Group recognizes that most Americans are not ready to see decisions made on “cost-effectiveness” alone.

But there is plenty of long-hanging fruit in the form of treatments that are less effective—and riskier—than less expensive alternatives. As we’ve discussed  in an earlier post, too often we often use advanced medical  technologies  on a broad swath of patients when only a few, who fit a very specific profile, actually benefit from it.

The TCF Working Group believes that next year, Congress may well authorize Medicare to negotiate for discounts on drugs for Medicare patients, and if so, it seems certain that Medicare would  take comparative risk and effectiveness into account when deciding how much it is willing to pay.

President-elect Obama made it clear that he believes that “drug negotiation is the right thing to do and the smart thing to do” in 2007, when the Senate failed to pass the Medicare Prescription Drug Price Negotiation Act. At the time, Obama  observed that the Senate had failed “ to consider a bill that would have placed the needs of seniors ahead of the profits of the health industry…Over the last decade the cost of drugs has quintupled, now totaling almost $200 billion. In 2005, the drug companies' profit was 16 percent of their revenues, compared to only 6 percent for all Fortune 500 firms…

“The growth in the cost of drugs has slowed in recent years, in part because of greater use of generic drugs. But given the price tag, and the financial challenges of our health care system, we can—and must—take additional steps to curb how much we are spending on drugs.

“When you look at the prices the Federal Government has negotiated for our veterans and military men and women, it is clear that the government can—and should—use its leverage to lower prices for our seniors as well.” In 2009, as Medicare searches for ways to cut costs, a new president may well find the votes to  pass the legislation.

Meanwhile, virtually everyone agrees that Medicare needs to adjust the fees that it pays doctors, raising reimbursements for primary care doctors, geriatricians, palliative care physicians and others who practice “cognitive medicine”—listening to and talking to patients. In a recession, Medicare will have to do this in what the Medicare Payment Advisory Commission (MedPac) calls a “budget-neutral way.” In other words, while hiking fees for doctors at the bottom of the income ladder, Medicare should trim fees for certain very expensive services when they are used too broadly, exposing patients to risk with little, if any, benefit.

Today, the fees Medicare pays physicians are determined by how much the service costs the physician in terms of time, mental effort  judgment, technical skill, physical effort and stress. But nowhere does “benefit to the patient” figure into the equation.  If Medicare took comparative effectiveness findings into account, private insurers, who already follow Medicare’s fee schedule, would be almost certain to follow suit.

Finally, as Medicare looks at the research, the Working Group believes that it would make sense to raise co-pays for tests and treatments that offer little benefit to certain patients. For example, as noted in a recent HealthBeat post, when it comes the mammograms, medical evidence has convinced the American College of Physicians that the dangers of unnecessary biopsies far outweighs the likelihood of saving a life for average risk women over the age of 74. (Similarly, the U.S. Preventive Services Task Force does not recommend mammography screening for women over 69). Older Medicare patients who still wanted the mammograms could have them, but they would have to pay more out-of-pocket. More importantly, news stories explaining why patients over 74 are being asked to pay more might well alert patients to the risks.

Why a Comparative Effectiveness Institute Would Make a  Difference

Just how much difference will an “Institute” make? Again, the Allhat story is informative. The Allhat research disappeared because the U.S. has no institution that advertises  comparative-effectiveness research and integrates it into  the decision-making process.

As the Times notes,  in order to try to spread the word about Allhat findings, “the federal Heart, Lung and Blood Institute  had to recruit Allhat investigators, provide them with training and  then sent them to proselytize fellow physicians. In all, 147 investigators gave nearly 1,700 talks and reached more than 18,000 doctors and other health care providers.”

In other words, the Allhat team had to convince doctors around the nation, one by one, that the results of its study should change the way that they prescribe blood pressure medication. Unfortunately, this effort was “a coffee-and-doughnuts operation compared with the sumptuous dinners that pharmaceutical companies used to market to doctors.” And it took the organizers a full three years to get the outreach up and running.

This is a profoundly inefficient way to try to promote change. You first need to transform a clinical trial into an advocacy operation, secure funding for outreach, coordinate nationwide networks of doctors, schedule countless meetings, and then work to win over doctors,. Worst of all, by the time such an endeavor gets off the ground, it may already be too late.

By the time your physician missionaries are equipped to spread the word, medicine may have already moved on. Earlier this year, for example, the Economist pointed out that one “comparative trial in the early 1990s laboriously compared balloon angioplasty and bypass surgery over the course of many years; but the widespread adoption of innovative heart stents in the meantime made the results of the study almost meaningless.” When it comes to assessing the effectiveness of a treatment, time is of the essence—because the health care industry will always try to keep one step ahead of objective evidence.

But what if we had a Federal Comparative-Effectiveness Research Institute?  Its recommendations could make headlines—especially if it was influencing Medicare fees and co-pays.  This would be bound to have an impact on how both patients and physicians perceive treatments. No physician has the time to keep up with, review and compare all of the research in his specialty. An unbiased Institute with a good website would serve as a clearing-house for information.

Patients versus Lobbyists

Of course lobbyists representing Big Pharma, device- makers and even some health care providers will fight legislation creating a Comparative Effectiveness Institute tooth and nail.

But that is why stories like the one that the Times just ran on Allhat are important. Today the mainstream press is making the public more and more aware that many health care treatments are not only over-priced but hazardous to our health. And an informed public is becoming wary.

Americans may love new medical technologies—but they do not enjoy being gouged, and they do not like being turned into unwitting guinea pigs.  They understand that overpriced treatments are driving insurance premiums skyward. Articles like the Allhat story, the Business Week cover story, “Do Cholesterol Drugs Do Any Good," or this piece in the New York Times–warning that angioplasty is not effective unless performed within three days after a heart attack—are drawing attention.

Indeed, some physicians are seeing the change in their practice. A couple of months ago, when Maggie saw a new primary care physician, she noted that her cholesterol is a little high and suggested Maggie start taking Lipitor, a cholesterol-lowering “statin”.

When Maggie began to explain her objections, the doctor pursed her lips and shook her head. “You know, these days I have a lot of patients like you say they won’t take statins.”

Maggie started to reply, ready to give the doctor a 20-minutes riff on ‘the cholesterol con’: “That’s because the research shows that for someone who hasn’t had a heart attack …” 

But the physician cut her off. “I am not interested in continuing my medical education,” she said crisply. Great.  Medical science stopped evolving the day she graduated. Clearly, a bad patient/doctor match.  (Maggie’s new PCP suggested that she eat fewer eggs.)

But, given the medical evidence, the fact so many patients are questioning statins  is a good sign. Lobbyists beware. Word is getting out.

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Comments

Cynthy

For the most part, profits rule the day. Recently, the efficacy of Lipitor, history's most profitable drug, is being questioned more frequently. Unfortunately, though, the "new" info isn't new at all.

Whether it be elevated C-reactive protein, low-density LDL, low HDL, high triglycerides, nothing yet has equaled the therapeutic effects of niacin, for which there's a sixty-year history of use.

Much is written about the use of niacin at www.cholesterolscore.com , which is a website that is primarily about niacin therapy.

Jon

Norvasc has been generic for the passed year and a half. ACE Inhibitors are mostly generic and cost pennies. Most great drugs go generic after 7 or less years. Diuretics have side effects such as frequent urination, hyperkalemia, etc. The reason why there is such a big market for high blood pressure medication is because America is FAT! Americans diets consist of huge fast food portions with high sodium. Where is the incentive for the pharmaceutical companies to come out with new generation drugs, when the regulations keep getting more stringent. If you did your homework, you would know that the new pharma guidelines say " no more taking doctors out to dinner, no more pens, pads, etc." Since when did a pen and a tuna fish sandwich ever influence someone? FYI - pharmaceutical drugs only account for 7% of all total healthcare costs. Its the other factors that need reform, such as the health insurance industry, where there is barely competition. If you want health insurance you have about 8 major companies to choose from. We need to bust these companies up and break them into 24 different companies, which will create a price war and drive down insurance premiums. As for the uninsured...Medicaid is a disaster...We must expand the doctors residency programs to treat the uninsured at facilities such as the VA hospitals, where there is some sort of infrastructure set up to treat patients. This would reduce the cost of Medicaid to the tax payers.
I feel most journalists are mis-informed and it bothers me tremendously when articles are written with just a fraction of the facts.

Avromie

There are many people out there who cannot take diuretics due to other complications, I agree with the previous post, this article is misinformed.

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I can provide charts, a protocol, results, cost analysis, and if there is interest a powerpoint conference that covers it all

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