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We have research on treatment efficacy — now let’s use it

The New York Times published a story this month 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’ 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 “stain”.

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.

Niko Karvounis tracks the health care system for the Century
Foundation
. Maggie Mahar is an award winning journalist and author. A
frequent
contributor to THCB, she is the author the
increasingly influential HealthBeat blog, one of our favorite health care reads and where this piece first appeared.

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9 replies »

  1. I was promoting an ARB when ALLHAT came out initially in 2002. I noticed Pfizer reps were promoting the ALLHAT trial in some way, as they had this trial in their possession at all times. Now I know why.
    A trial came out recently which I think was called the ACCOMPLISH trial, that showed a combo drug of a CCB with an ACE was better than a diuretic and an ACE inhibitor combo drug. However, this trial was sponsored by Novartis, who remarkably markets Lotrel, which is Norvasc and Lotensin, an ACE inhibitor. What a concidence:
    Cardiovascular disease, I surmise, is very concerning to both patients and their care givers, if this disease is expected, or in fact does exist. Furthermore, this disease is likely a cause of distress as well as confusion for many who seek the best treatment options for such diseases. As a result, there are increasingly many pharmacological options available to delay if not prevent such diseases, and these drugs work in different ways for the same cardiovascular diseases that are acquired often. Many health care providers are understandably unclear as to which treatment option would be most beneficial for their cardiac patient.
    One increasingly progressing cardiovascular disorder is hypertension, or high blood pressure, as it affects possibly over 70 million Americans- many of which are not either treated or have their hypertension controlled as it needs to be to prevent future cardiovascular events caused by prolonged hypertension in such individuals. Such events include an increased risk for strokes, heart attacks, and kidney failure, among other damage that can be caused in the unmanaged hypertensive patient. While hypertension is evaluated according to different stages of severity, most hypertensive patients have what is called primary, or essential hypertension, and often require medicinal treatment to control their high blood pressure.
    Additional reassurance for health care providers was made available regarding which pharmacological therapy for hypertension should be chosen by them due to the results of the ALLHAT trial. This trial lasted 4 years and was published in the Journal of the American Medical Association in 2002. Also, the trial was conceptualized and implemented by the National Institute of Health during the 1990s. This trial was the largest study to date addressing, among other variables, those patients in the study with hypertension, and the study examined which class of medications were most effective for these types of patients placed on these different classes of medications for their hypertension treatment that were involved to be studied
    in the ALLHAT trial. In addition, the ALLHAT trial included over 40,000 subjects who were over the age of 55 and were evaluated in over 600 clinics during the course of this trial. Nearly half of the patients in this trial had metabolic syndrome, which is a syndrome where one is obese, has dyslipidemia, and glycemic issues as well. While Pfizer financially contributed a small portion to support this trial, ALLHAT was overall funded by the National Institutes of Health at a cost of around 130 million dollars, which again was for the purpose to determine the best medicinal treatment for the patients that were studied in this trial according to the trial’s study plan to compare the effectiveness of the different classes of medications in this trial, which had not been done to this degree in the past.
    Because the NIH developed and funded this study, the ALLHAT trial, as a result, was largely if not completely void of bias and commercial interference compared with those trials that are sponsored by the manufacturers of drugs studied in other trials often. Because of the ideal design and methodology in which this trial was performed, most concur the results of this trial are quite accurate and valid that demonstrated the effectiveness of each class of medications in the ALLHAT trial.
    ALLHAT provided data that allowed a true comparative analysis of these various classes of drugs for hypertension, which included calcium channel blockers, ACE inhibitors, Alpha Blockers, Beta Blockers, and diuretics. The researchers examined the action of these classes of medications on the subjects who possessed various cardiovascular disease states- with a focus on the ability of each one of these different classes of drugs on the disease of hypertension the patients in the study had during the trial. As the trial was completed with data collected and analyzed after a 4 year period, the ALLHAT trial concluded that one particular class of medications involved in this study proved to be the most advantageous for the subjects as it relates to safety, efficacy and cost for those who require treatment for their cardiovascular disease state, as well as the prevention or the delay of progression of additional cardiovascular disease states studied and examined. Amazingly, this one drug class in this study is in fact nearly as old as the subjects involved in the trial.
    ALLHAT results specifically and clearly concluded that thiazide diuretics are, overall, the preferred choice of initial medicinal therapy for hypertensive patients, as this class of drugs overall proved to be equivalent if not superior in many ways compared with the other classes of drugs in the study. Diuretics offered great protection against cardiovascular disease and controlled hypertensive patients as they needed to be, and proved that diuretics should be the first line drug of choice in such patients. The diuretics also decreased the risk of heart failure and stroke, as well, compared with the other classes of drugs in this trial. Thiazide diuretics were in fact superior in these risk factors in this comparative effectiveness protocol, and just as effective as the other classes of drugs it was compared to in this trial with preventing myocardial infarctions. Thiazide diuretics in fact have been studied in such disease states associated with cardiovascular disease for over 40 years.
    This class of medications, diuretics, have been available in the United States for well over 50 years, and presently costs about 25 dollars a year, instead of a few dollars a day for many if not most branded medications for CV conditions that were examined in the ALLHAT trial. So this finding, of course, concludes that diuretics not only provide equivalent if not superior benefits for cardiovascular disease patients, but also provides cost savings as well as illustrated in this trial. The ALLHAT trial was rare and unique in that it compared diuretics to these other classes of medications directly, which is not done frequently with clinical trials involving branded pharmaceuticals, as they usually do comparative studies with simply placebos most of the time, so their efficacy comes into question as a result.
    Yet, even though this trial was potentially beneficial for so many who are involved with prescribing medications such as diruetics reasonably and necessary for their hypertensive patients, the acknowledgement of diuretics as being superior and preferred as initial medicinal therapy never really materialized or was fully recognized following the release of the results of the ALLHAT trial by the medical community, and this diuretic still is not utilized as often as it should be, according to others. There was hope that there would be an increase in the prescribing of diuretics based on the results of this trial for those patients who are determined to have the disease states in the ALLHAT trial. Even after the researchers of the ALLHAT trial implemented what was called an ALLHAT dissemination plan from the years 2003 to 2006 at a cost of close to 4 million dollars to educate health care providers about the ALLHAT results, and the significance of the findings, the acknowledgement of the benefits of diuretics continue to be unrecognized by health care providers who select other classes of drugs to treat their hypertensive patients, as they still do today. The other classes aside from diuretics do in fact have benefits with cardiovascular patients, with compelling indications in particular. Yet the etiology for the prescribing habits regarding diuretics and why this class of medications is not chosen as often as they should be is largely unknown
    Others have speculated why this issue with diuretics in the ALLHAT trial never caught the attention to change the prescribing habits of health care providers, overall.
    For example, and of no great surprise, these results of the ALLHAT study appeared to be of notable concern to those pharmaceutical companies who promote the other classes of medications in the ALLHAT trial that are more expensive than a thiazide diuretic. Reportedly, these companies who market these other classes of drugs increased their promotional spending in order to blunt the potential effects this trial may have on the usage of their cardiovascular medications that again belong to the classes that were involved in the ALLHAT trial soon after the results from this trial were published. Sampling of their branded medications to health care providers increased noticeably as well from those pharmaceutical companies that had branded medications for cardiovascular disease states. Thiazide diuretics, while clearly the apex for the prevention and management of hypertension and other cardiovascular disease states, do not engage in this promotional behavior that appears to be more of a powerful force than evidence-based medicine, as with the case of this diuretic and the benefits of this class of drugs that has been discussed..
    Furthermore, drugs combining two medications from different classes of medications for hypertension and other cardiovascular disease states are increasingly preferred by many health care providers for understandable reasons presently- depending on the severity of the cardiovascular disease states that may exist, along with the risk of developing these cardiovascular conditions. It has been said that nearly 70 percent of hypertensive patients alone require more than one medication to adequately have their hypertension controlled. It is not unusual, for example, for a branded pharmaceutical company to combine their medication for hypertension with a diuretic for those patients that may have a stage of hypertension that requires simply more than just one drug for reduction of their high blood pressure. On the other hand, some cardiovascular combination medications are absent of a diuretic. Yet diuretics remain the first line choice of treatment based on the results of the ALLHAT trial, regardless, and should be included in any combination drug chosen for the treatment of most cardiovascular disease patients with hypertension that requires more than one drug for control of their high blood pressure, according to others.
    More convincing is that the JNC-7, a report that concludes which medication is best for the prevention and treatment of high blood pressure as well as other cardiovascular conditions, concurs with the results of the ALLHAT trial, and as a result, the JNC states in their report that diuretics are preferred for first-step hypertension therapy, and acknowledge that this class of medications is presently under-utilized. The Report is rather thorough, and is developed by the American Heart Association. The report is also recognized and respected by health care providers who treat cardiovascular disease.
    I’m comfortable as a layperson in suggesting that the cardiovascular experts should and in fact be obligated to continue to make others aware of the results of the ALLHAT trial, and convince other health care providers that diuretics should be the preferred choice of medicinal therapy for the medical conditions illustrated and treated in the ALLHAT trial. . In particular, thiazide diuretics are most beneficial for those hypertensive patients that are African American, the elderly, obese patients, those with heart failure, or those with chronic kidney disease, others have concluded. And it should be noted that this type of diuretic depletes potassium from the patient taking this drug, so caution should be utilized regarding this issue, as well as the patient who is prescribed a diuretic should be informed of additional possible side effects associated with a thiazide diuretic, although they are infrequent.
    Along with the cost savings that could amount to billions of dollars saved annually, diuretic medicinal therapy would ensure both health care provider and patients that they are receiving the proven and ideal treatment which will control their hypertension, and delay the progression and prevent additional cardiovascular events with this particular drug.
    Unfortunately, it appears what may be one of the most authentic trials conducted has been and continues to be largely disregarded or not recalled by those who treat hypertension- possibly due to the forces of others whose objectives are of a different nature besides the restoration of the health of others as it relates to the diseases addressed in the ALLHAT trial. So again, it appears in this situation that promotion has been a more powerful force than what science has provided.
    Dan Abshear

  2. Not withstanding the opinions Mr. Pollack expressed in his poorly written and misleading newspaper story, hypertension is one of those areas where the research is broadly known. The recent heaving and sighing over the 2002 ALLHAT study is a pretty good example of the difficulty of analyzing study results. The ALLHAT trial is an outlier among trials which otherwise lean slightly in the direction of the ACE-I for HTN treatment.
    How does a clinical physician evaluate RCTs? I’m a community doc, not an academic. I have neither the tools nor the time to ponder the significance of each individual study as it is released. As a result, I tend to go by the recommendations of the experts. In the case of hypertension, the JNC VII is widely regarded as the standard of care. Although it is obviously influenced by the quirky ALLHAT trial, it’s clear that the Joint National Committee also took the rest of the trial literature into account when formulating their recommendations. There is no competing standard that I’m aware of. The ADA and the AHA point their recommendations for blood pressure control back to the JNC VII. However, for other areas of medicine it is not clear which recommendation to follow and Mr. Pollack might have had a much stronger article had he looked elsewhere. Compare the USPSTF PSA testing recommendation vs. the AUA’s recommendations — two panels of experts who come to opposite conclusions.
    There is already a lot of comparative effectiveness data available — of varying quality, but it is often contradictory and reconciling those differences is not easy. Your Institute of Comparative Effectiveness would probably wind up depending on expert opinion too.
    Just in case anyone wants to quantify the cost difference between the inexpensive diuretic tested in the ALLHAT (which is not the one Mr. Pollack refers to — the authors of the ALLHAT make it clear that in their opinion this is not an appropriate choice) and the ACE-I costing “up to 20 times as much” check drugstore.com. At current prices a 360 day supply would be $119.95 for chlorthalidone 25mg vs. $127.94 for Lisinopril 20mg. Technically, $7.99 per year would make the “up to” cut, but I’m inclined to view it as a tiny exaggeration. Many experts feel that the ALLHAT had a design flaw that tilted the field in favor of the diuretic. However, in primary endpoints the three drugs performed identically. In sub-group analysis for secondary endpoints there were small, but statistically significant differences in a few areas. Other studies (e.g. the ANBP2) have led to different conclusions.
    Young Mr. Klein needn’t be so glum about the difficulty of persuading patients and physicians to switch to generics. The system that we use in California works well. When a patient wants a name-brand medication, the physician generally has to fill out a form, the patient has to pay a higher co-pay, and the pharmacist is paid a smaller filling fee. Whether I write the prescription using the generic name or the brand name, the prescription still gets filled with the patient’s (or sometimes the pharmacist’s!) preference. All three of us are motivated to choose a generic under this scheme.
    MG: EMRs are not yet at the fuzzy logic stage that will allow them to make recommendations for patients. Apparently there isn’t enough money in the field to attract the skilled designers that something like Google Chrome can attract. The current offerings are oriented toward billing considerations. You can, with enough patience, generate handsome notes, but beyond that they have yet to venture. I’d be happier with ours if it would remain functional for the entire day….

  3. Unless this has real financial teeth that impacts patients and providers, it will largely be for not.
    Additionally, the key details are what types of evidence are used to make and judge effectiveness. After having experience doing meta-analysis, it is a messy and difficult affair.
    Here are just a couple of questions that come to mind:
    1. Do you use studies/results based on upon solely upon observational data? If so, what are the specific criteria?
    2. Do you include results from studies in other countries including Europe, Japan, and others?
    You could easily add another dozen or so questions to this list. In fact, it would become pretty lengthy and likely varies considerably from topic to topic.
    I don’t question the intention of using EBM to guide diagnosis and treatment decisions. Ideally it is the right thing to do I just question the ability to generate EBM that is timely, accurate, and actually impacts medical practice in a meaningful way.

  4. Deron S. and Bev MD–
    Thanks muh for your comments. (I’ll come back and reply to the rest of the comments tomorrow. )
    Deron S,
    Thanks for the kind words.
    And I agree that the comparative effectiveness
    info needz to be readily accessible in EMR system
    so that physicians can access it on the spot. (I beleive this happens at the VA, which has made good use of its database to see what works and what doesn’t for patients who fit a particular profile. I’m pretty sure it happens at Mayo and probably Kaiser.)
    I also agree that, Yes, financial incentives are needed to motivate providers to use the research. Long-term, we need to move away from fee-for service. Short-term, we need to adjust fee for service to reward docs who are following guidelines based on current evidence (which will always change–thisis why it needs to be embedded in EMR.
    As to whether Pharma should be at the table: I entirely agree with you and Bev M.D. that there are many excellent scientists wokring within the drug industry. But as Dr Jerry Avorn has pointed out in his book, their voices are not heard when final decisions are made: We need need to save the drug industry from its marketing people.
    But, from the late 1980s to the late 1990 I covered Wall Street for Barron’s, and wrote many stories about Big Pharma.
    Here’s the truth: The marketing people have the ear of the CEO. The researchers do not. And a researcher who “sits at the table” and speaks against what the “line people” (those who bring money into the company) will lose his job. (It’s also very unlikely that he will be the person the company sends to the table. They will find a compliant scientist.)
    After ocvering Wall Stret for years, I’m afraid I really have to say: it really is that simple. (The best and most honest analysts on Wall Street agree.) Any scientist who tries to tell a truth that might diminish corporate profits– whether in the drug industry, the tobacco industry, or the auto industry– will simply be fired or put in a position where he will finally quit.
    –bev m.d.
    Good to hear from you.
    I grinned out loud when you said that you laughed out
    loud at the thought of my encounter with the
    PCP who wanted to put me on Lipitor.
    Definitely a terrible doc/patient match
    –on both sides of the equation.
    But the fact that she said “I have many
    patients like you” (with real disdain)
    strikes me that she is ignoring the concerns
    of many patients.
    On Pharma at the table: I absolutely agree that there
    are many scientists in the industry who are excellent.
    But, when compared to the marketing people (who then become the CEOs), they have little power. This I know
    from my years at Barron’s.
    On this issue, please scroll up to my reply to Deron –right above my reply to you.

  5. I agree with both Deron and Bev but for different reasons. I believe that for CE to succeed means getting all of the principle contributors to understand how a clinical trial is conducted and most importantly, why. In situations where gross assumptions have been made that each “player” around the table at a CE meeting knows what the other’s job is has led to policy and business decisions being made that are costly for the product, the prescriber and the patient. It seems like a small thing but it is highly powerful – get people communicating in the same language. I have seen it work in situations where the clinical people have taken the time to explain the nuances of the trial design and most importantly, what they are looking for in designing the trial that way.
    In addition, it would be a disappointment for the Commission’s early actions to be clouded with the participants’ conclusion that the trial designs are such because “the FDA made us do it.” The FDA needs to be at the table too.

  6. The Gold Standard For The Management of Your Heart
    Cardiovascular disease, I surmise, is very concerning to both patients and their care givers. Furthermore, this disease is likely a cause of distress as well as confusion for many who seek the best treatment, once the disease presents itself. As a result, there are increasingly many pharmacological options available to delay if not prevent such diseases, yet many health care providers were understandably unclear as to which choice is the most effective with these deadly disease states manifested by substandard cardiovascular function.
    Hypertension, or high blood pressure, affects possibly over 70 million Americans- many of which are not either treated or have their hypertension controlled as it needs to be to prevent various cardiovascular events caused by prolonged hypertension in such individuals. Such events include an increased risk for strokes, heart attacks, and kidney failure, among other damage that can be caused in the unmanaged hypertensive patient.
    Additional reassurance was made available regarding which pharmacological therapy for hypertension should be chosen by health care providers due to the results of the ALLHAT trial, which was published in the Journal of the American Medical Association in 2002, and was conceptualized and implemented by the National Institute of Health. This trial was the largest study to date addressing, among other variables, those patients in the study with hypertension, and which class of medications was most effective for these types of patients of the different classes of medications for hypertension treatment that were studied in the ALLHAT trial. In addition, the ALLHAT trial included over 40,000 subjects over the age of 55 who were evaluated in over 600 clinics during the course of this trial. Nearly half of the patients in this trial had metabolic syndrome, which is a syndrome where one is obese, has dyslipidemia, and glycemic issues as well. While Pfizer financially contributed a small portion to support this trial, ALLHAT was overall funded by the National Institutes of Health at a cost of around 130 million dollars, which again was for the purpose to determine the best medicinal treatment for the patients that were studied in this trial according to the trial’s study plan to compare the effectiveness of the different classes of medications in this trial.
    Because the NIH developed and funded this study, the ALLHAT trial, as a result, was largely if not completely void of bias and commercial interference, as there was no relevant association between the trial investigators and the makers of the drugs studied in this trial. In addition, there was no commercial sponsor for this trial, which is typically the way clinical trials are conducted presently. Because of the ideal design and methodology in which this trial was performed, most concur the results of this trial are quite accurate and valid.
    ALLHAT provided data that allowed a true comparative analysis of these various classes of drugs for hypertension, which included calcium channel blockers, ACE inhibitors, Alpha Blockers, Beta Blockers, and diuretics. The researchers examined the action of these classes of medications on the subjects who possessed various cardiovascular disease states- with a focus on the effects of these different classes of drugs on the disease of hypertension the patients in the study had during the trial. As the trial was completed with data collected over a 4 year period, the ALLHAT trial concluded that one particular class of medications involved in this study proved to be the most advantageous for the subjects as it relates to efficacy and cost for those who require treatment as well as prevention of additional cardiovascular disease states studied and examined. Amazingly, this one drug class in this study is in fact nearly as old as the subjects involved in the trial.
    ALLHAT results specifically and clearly concluded that thiazide diuretics are, overall, the preferred choice of initial medicinal therapy for hypertensive patients, as this class of drugs overall proved to be more beneficial in many ways compared with the other classes of drugs in the study, which proved to be not any better or safer than diuretics. Diuretics offered great protection against cardiovascular disease, and proved that diuretics should be the first line drug of choice in such patients. The diuretics decreased the risk of heart failure and stroke, as well as providing adequate reduction in blood pressure of the hypertensive patients in the study. Thiazide diuretics have proven similar benefits with other clinical trials, in fact, for over 40 years.
    This class of medications, diuretics, have been available in the United States for well over 50 years, and presently costs about 25 dollars a year, instead of a few dollars a day for many if not most branded medications for CV conditions that were examined in the ALLHAT trial. So this finding, of course, concludes that diuretics not only provide equivalent if not superior benefits for cardiovascular disease patients, but also provides cost savings as well as illustrated in this trial. The ALLHAT trial was rare and unique in that it compared diuretics to these other classes of medications directly, which is not done frequently with clinical trials involving branded pharmaceuticals, as they usually do comparative studies with simply placebos most of the time.
    Yet, even though this trial was potentially beneficial for so many who are involved with prescribing diruetics reasonably and necessary for their hypertensive patients, the acknowledgement of diuretics as being superior and preferred as initial medicinal therapy never really materialized or was fully recognized following the release of the results of the ALLHAT trial by the medical community. There was hope that there would be an increase in the utilization of diuretics based on the results of this trial. Even after the researchers of the ALLHAT trial implemented an ALLHAT dissemination plan from the years 2003 to 2006, at a cost of close to 4 million dollars, to educate health care providers about the ALLHAT results, and the significance of the findings, the acknowledgement of the benefits of diuretics continued to be unrecognized by health care providers who continued to select other classes of drugs to treat their hypertensive patients, as they still do today. And the reasons for this prescribing behavior may be unknown, yet others have speculated why this issue with diuretics in the ALLHAT trial never caught the attention to change the prescribing habits of health care providers, overall.
    Of no great surprise, these results of the ALLHAT study appeared to be of notable concern to those pharmaceutical companies who promote the other classes of medications in the ALLHAT trial. Reportedly, these companies increased their promotional spending in order to blunt the potential effects this trial may have on the usage of their cardiovascular medications that belong to the classes that were involved in the ALLHAT trial soon after the results from this trial were published. Sampling of their branded medications to health care providers increased noticeably as well from those pharmaceutical companies that had branded medications for cardiovascular disease states. Thiazide diuretics, while clearly the apex for the prevention and management of hypertension, do not engage in this promotional behavior that appears to be more of a powerful force than evidence-based approaches, as with the case of this diuretic and the evidence behind this class of medications that has been discussed.
    Furthermore, drugs combining two medications from different classes of medications for hypertension and other cardiovascular disease states are increasingly preferred by many health care providers for understandable reasons presently- depending on the severity of the cardiovascular disease states that may exist, along with the risk of developing these cardiovascular conditions. It has been said that nearly 70 percent of hypertensive patients require more than one medication to adequately have their hypertension controlled. It is not unusual, for example, for a branded pharmaceutical company to combine their medication for hypertension with a diuretic for those patients that may have a stage of hypertension that requires simply more than just one drug for reduction of their high blood pressure. Yet diuretics remain the first line choice of treatment based on the results of the ALLHAT trial, regardless, and should be included in any combination drug chosen for the treatment of most cardiovascular disease patients with hypertension that requires more than one drug for control of their high blood pressure.
    More convincing is that the JNC-7, a report that concludes which medication is best for the prevention and treatment of high blood pressure, concurs with the results of the ALLHAT trial, and as a result, as they state in this report that diuretics are preferred for first-step hypertension therapy, and acknowledge that this class of medications is presently under-utilized. The Report is rather thorough, and is developed by the American Heart Association.
    I’m comfortable as a layperson in suggesting that the cardiovascular experts should and in fact be obligated to continue to make others aware of the results of the ALLHAT trial, and convince other health care providers that diuretics should be the preferred choice of medicinal therapy for the medical conditions illustrated and treated in the ALLHAT trial. . In particular, thiazide diuretics are most beneficial for those hypertensive patients that are African American, the elderly, obese patients, those with heart failure, or those with chronic kidney disease, others have concluded. And it should be noted that this type of diuretic depletes potassium from the patient taking this drug, so caution should be utilized regarding this issue, as well as the patient who is prescribed a diuretic should be informed of additional possible side effects associated with a thiazide diuretic, although they are infrequent.
    Along with the cost savings that could amount to billions of dollars saved annually, diuretic medicinal therapy would ensure both health care provider and patients that they are receiving the proven and ideal treatment which will control their hypertension, and delay the progression and prevent additional cardiovascular events with this particular drug.
    Unfortunately, it appears what may be one of the most authentic trials conducted has been and continues to be largely disregarded or not recalled by those who treat hypertension- possibly due to the forces of others whose objectives are of a different nature besides the restoration of the health of others as it relates to the diseases addressed in the ALLHAT trial. So again, it appears in this situation that promotion has been a more powerful force than what science has provided.
    Dan Abshear

  7. I agree with Deron; let the scientists from Pharma sit at the table, not the salesmen. One forgets there ARE scientists at these companies, who know what they are doing.
    The post also raises an important point about any future comparative effectiveness institute – in addition to performing its own research, it could spend huge amounts of useful time collating and evaluating the many comparative effectiveness studies (such as the one exemplified) already out there.
    And BTW, I laughed out loud about Maggie and her PCP regarding statins! (The doc wasn’t saying she didn’t want to continue her education; she was responding to being lectured). I can just imagine that exchange, having had a few with Maggie myself! Glad you found another one to fit your needs.

  8. I like the concept of an unbiased institute with a good website, but it probably needs to go beyond that. The information needs to be better distributed to the clinical decision making points in the system. It needs to be integrated into EMR systems so that a physician can efficiently access it during the flow of a busy patient schedule.
    Unfortunately, I’m not sure this initiative alone will cut out a majority of the waste. I don’t think it can effectively address overtreatment caused by defensive medicine and financial incentives to order tests. Other steps must also be taken in conjunction with the evidence-based movement.
    I disagree that drug companies shouldn’t be at the table however. It’s tempting to say they shouldn’t be considering the astronomical profits they make, but physicians and patients are also not without fault in the system and I wouldn’t want to exclude them. I would suggest that someone from R&D represent big pharma as opposed to one of the CEOs.
    Great post by the way!

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