Focusing on High-Impact Comparative Studies: Cardiovascular Disease in the Spotlight

Fifty years ago, President Lyndon Johnson signed designated February as American Heart Month to acknowledge and combat the “staggering physical and economic loss to the nation” caused by cardiovascular disease.

Unfortunately, that proclamation is proving to be a timeless document.

Even with broad awareness of heart disease, expansive research and a number of clinical and public health efforts to prevent, diagnose and treat cardiovascular conditions, it remains the leading cause of death in the nation. About 600,000 people die from heart disease in the United States each year—making it responsible for one out of every four American deaths.

As a research institute dedicated to helping patients and those who care for them make better informed decisions that lead to better outcomes, the Patient-Centered Outcomes Research Institute (PCORI) is acutely interested in producing new information that supports more effective cardiovascular care. The directive in our establishing legislation to consider “disease incidence, prevalence, and burden” when prioritizing research funding is a clear call for studies of cardiovascular conditions.

I’m proud to say that PCORI has answered that call. Cardiovascular disease, including heart disease and stroke, is the most commonly studied topic in our research portfolio. It is addressed in several dozen of the 192 primary research studies that PCORI has funded to date, including projects that conduct a comparative assessment of heart disease interventions, as well as those that test the effectiveness of decision support tools. Communicating information and providing tools to patients in ways that motivate them to make healthy choices is often a major challenge for clinicians.

Our comprehensive approach funds research that addresses the gaps in both information and communication that are responsible for poor outcomes in cardiovascular care.

One study being conducted by Brigham and Women’s Hospital in Boston is testing a strategy for preventing cardiovascular disease in women who suffered from pre-eclampsia, a condition of high blood pressure during pregnancy that is recognized as an early warning sign for heart disease. There currently are no programs designed specifically to inform young women with recent pre-eclampsia of their risk and to help them make appropriate lifestyle changes. In a randomized controlled trial, researchers will test the effectiveness of a web-based program in promoting proper nutrition and physical activity, and in encouraging women to speak with their primary care provider about their risks.

In 2012, the American Heart Association (AHA), in its comments to PCORI regarding our research priorities, emphasized the need to develop decision aids for heart failure patients to enhance shared decision making. A PCORI study under way at the Baylor College of Medicine in Houston tests the success of a decision support aid to help patients understand the benefits and trade-offs of ventricular assist devices (VADs), which are becoming much more common. VADs following heart failure can prolong life by up to five years, but they may harm quality of life and carry risks of neurological complications, infections, and multi-organ failure. The decision aid seeks to present outcomes, risks, experiences, and uncertainties about VAD placement in a clear, comprehensive, scientifically valid, and unbiased manner.

Studies like these address the real world challenges that patients and front-line clinicians face in supporting cardiovascular health. We are confident that the resulting findings will be relevant and useful in everyday clinical practice.

PCORI is launching an additional funding program in 2014 that will accelerate the creation of valuable research findings. Beginning this year, the institute will fund large pragmatic studies that focus on direct comparisons of drugs, devices and other forms of prevention, diagnosis and treatment to determine what works best for patients given their individual preferences. The focus of our initial funding will include 15 high-priority topics, one of them being the reduction of cardiovascular disease risk in underserved populations, such as racial and ethnic minorities and those living in rural communities. With substantial research investment, we can help communities with a high prevalence of poorly managed heart conditions achieve better outcomes.

The proclamation signed by President Johnson 50 years ago still resonates in more ways than just our persistent struggle with heart disease.  It said the expansion of programs to support cardiovascular health, such as research that studies “methods of prevention, diagnosis, and treatment of the cardiovascular diseases,” gives us hope that we “may eventually eliminate these diseases as important causes of death.” The promise of reliable research still rings true today.

We welcome your support as we seek to reduce the pain that heart disease inflicts on millions of Americans. Please visit us at pcori.org to find out more about our work and how you can play a meaningful role in research that helps patients receive the best care possible.

Joe Selby, MD, MPH, is PCORI’s Executive Director. You can read more from him in The PCORI Blog. Information on PCORI’s funding opportunities and engagement programs also can be found on pcori.org.


21 replies »

  1. It’s really a great job to focus on cardiovascular diseases.Success of these studies will cause a deep relief to the patients who are suffering from this disease.Hoping for good.All the best!!

  2. “what would you prefer we die from?”

    Being taken advantage of by a 20 year old nymphomaniac in a bikini.

    Seriously, nobody wants to die of anything except “old age”.

    I have sat around the lunch table with Cardiologists and Oncologists. The Oncologists consider it a “win” if the patient dies of heart disease. The Cardiologists consider it a “win” if the patient dies of cancer.

    I want to die in my sleep.

  3. “once you concede that a nation’s entire GDP is not going to be spent saving one life, the rest is a quibble over the price, not principle.”


    See Elhauge, 1994, “Allocating Health Care Morally”

  4. I agree you need an anchor; such as cost per quality-adjusted life year. Where I trained (Britain’s NHS) not many found the idea that there is a finite cost of a life repugnant. You wouldn’t get much traction with death panels there, other than perhaps for a Monty Python sketch.

    The culture is different here.

    There are problems in defining outcomes that are not hard core cause-specific mortalities, such as utilities from various health states.

    But society is picking up the tab for society, so rational planning is necessary.

    I do think the small effects part sorts itself out. Smaller the effect, the larger the sample size, the less likely there is statistical significance. It’s a self-correcting mechanism.

    For all its warts, comparative effectiveness is the best we have.

    The absence of a genuine debate on healthcare, genuine from the trenches led by non-ideological physicians, means that society still has not grasped a basic fact: once you concede that a nation’s entire GDP is not going to be spent saving one life, the rest is a quibble over the price, not principle.

    If comparative effectiveness, rather than cost effectiveness, helps people sleep better at night, so be it.

  5. That’s an appealing analogy, particularly for someone like me who knows a dram or more about malts. But rather than play with the analogy, let’s take your ICD example. There are very, very few clinical circumstances where there is substantive data for the efficacy of the ICD, and many where efficacy has proved elusive. Let’s assume you want to apply your “worth it factor” to the former, is it “worth it” to place the newer ICD rather than the old version? “Worth it” for what and at what risk and at what cost? How likely is a patient with a ICD to need a MRI? How reliable is the new ICD over time? Do you think CER can answer any of these questions? Do you think an elegant RCT would be better suited? How would you power such an RCT?

    I am a zealot for “outcomes research” and for informed medical decision making. However, I am also aware of inherent limitations of what I call “small effectology”. Is there a term for epidemiologic hubris other than epidemiologic hubris?

  6. Agree with @Saurabh.

    This conservation has been seriously one sided to this point.

    The idea here is to study both popular and unpopular drugs and devices to get some sort of handle on a field that is currently dominated by studies that clearly ARE influenced by commercial interests.

    The conspiracy theorists are assuming the point here is to rubber stamp and deny. Well, that’s a little too cynical for me. Will special interests try to influence the process? Absolutely. Hell, they do in every other area in medicine and government – why not here? The reality may be that creating a perfect laboratory environment will be difficult, but does that mean we should give up?

    I’m not quite ready to do that.

  7. In defense of PCORI….

    There would be more lawlessness without CER. Industry would be putting out device and drugs with dubious incremental, key is incremental, benefits. There would be even more “me too” agents.

    It’s different when you are buying scotch. Blue label costs for than red label for tangible reasons.

    How would you know new MRI-compatible dual chamber ICD is Blue label or Red Label?

    By outcomes. Outcomes are the “worth it factor”.

    But measuring outcomes needs aggregation, standardization and planning.

    CER reduces uncertainty with regards to technology adoption. Uncertainty costs.

    It would be different if healthcare was a pure free market. But it’s not.

  8. Dr. Wes, you give the “academic elite” too much credit. The motivation behind the ACA was and is universal access to health care. The stumbling blocks to enactment were the definition of “health care” and the cost of its provision. PCORI and CER are an ill advised attempt to breach the former. The “cost” term appeared frequently in the draft legislation but was red-lined out in committee. Even PCORI is not to assess cost-effectiveness (which is feasible), only effectiveness. Hence, the ACA is a cash-Calf for academics seeking PCORI funding, but it is a cash-Cow for so many other stakeholders and a travesty for the health of the American people. It is another example in the litany of unintended consequences of “health care” legislation starting with Medicare
    When will we ever learn?

  9. Pat –
    You say “That’s not correct. AHRQ has phased out of its budget funding for CER. All that’s left is training and dissemination work. ”

    In this statement, you confirm my premise – that AHRQ was already tasked with performing CER.

    But this is only the tip of the iceberg, IMO. You see, the foundation for the PCORI was laid, not with the ACA, but with the 2009 American Reinvestment and Recovery Act as a favor for the “stakeholders,” defined by your document as universities, medical centers, hospitals, purchasers, payers, policymakers, nursing homes, and research institutions throughout the country and abroad.” Nowhere are patients or the clinical doctors who care for them part of this process. And because the AHRQ is slated to receive up to $100 million directly funneled from PCORI (by law, thanks to the ACA) to support its “research”, thereby increasing its research budget (that is heavily directed toward insurers’ interests, rather than patients) we see a huge money-laundering scheme for research biased toward “stakeholders” rather than patients.

    From your document (page 25):
    “The FY 2014 President’s Budget provides $100.0 million for the Patient-Centered Health Research (PCHR) portfolio, an increase of $59.4 million from the FY 2012 Actual level. The entirety of the increase is attributable to mandatory funds transferred to AHRQ from the Patient-Centered Outcomes Research Trust Fund. As authorized in section 937 of the Public Health Service Act, AHRQ will disseminate research findings from the Patient-Centered Outcomes Research Institute and other government- funded comparative clinical effectiveness research and build research and data capacity for comparative clinical effectiveness research.”

    The PCORI was a clever, but incredibly expensive and non-transparent, end-run for the academic elite to further inflate the bureaucracy in Washington at patients’ expense.

  10. I feel for Dr. Selby….I guess he didn’t know what he was getting into
    by posting here. Informative and illuminating posts…..thanks.

  11. I didn’t enshrine Irene’s comment in a Twitter message just to be cute. As Dr. Hadler pointed out an aging population has a lot to do with trends and statistics.

    As a caregiver for other old people in my post-retirement years I see too many examples of demented people kept alive way too long by the magic of science. I have also seen people in their nineties who remain mentally sharp, physically nimble and well-coordinated. The variables have as much to do with genes, lifestyle, stress and diet as with medical care, drugs and/or devices and therapies.

    It’s easy to be too close to an issue — in this case the efficacy of various heart disease treatments — and risk missing the question of appropriateness. I’m less prissy about the subject than I once was. While discussing living well we also need to discuss dying well. I realize that living people are more impressive (and profitable) than those who die, but sometimes living longer ain’t all it’s cracked up to be.

  12. It’s a (largely superfluous and duplicative) government agency, so it would be more like incomparably ineffective research.

  13. LVADs have been the subject of many observational studies in the setting of the acute MI complicated by cardiogenic shock. Even the Cochrane Collaboration agrees that there is no reason to assume they are effective based on the available science.
    The commonest LVAD used currently is the IABP (percutaneously inserted intra-aortic balloon pump), offered nothing of substance to the prognosis of these patients in a recent RCT: http://www.nejm.org/doi/full/10.1056/NEJMoa1208410

    Before we worry about cost-effectiveness, we need some substantive evidence for efficacy. If it doesn’t work, who would want it even gratis. And before PCORI worries about LVAD’s comparative effectiveness, don’t they need to know that LVADs works in some subset. Otherwise, they may be doing comparative ineffectiveness research.

  14. I am all for reducing premature morbidity and mortality from CVD, but unfortunately, that’s not what this post is about. It’s about mythology or, rather, the perpetuation of a myth. As Irene K correctly notes, age-adjusted heart disease mortality is dropping. In 2010 there were 379,543 coronary heart disease deaths in the US and 323,744 (85%) happened in men and women over age 65, which means they weren’t killed by infectious disease or injuries that used kill our ancestors. Deaths from hyptertension and stroke are similarly much more common in the elderly than in younger age bands. I agree also with Nortin’s lament that we simply use the CVD/CHD check box on death certificates in the elderly because it’s easy and no one is going to order autopsies to adjudicate a true final cause.

    This “CVD is killing us” whine is reminiscent of what wellness vendors tell employers. They breathlessly proclaim CVD will fell the entire employee group if not contravened forthwith. Never mind that the median of the US workforce in 2010 was 42, and that there were only about 5,000 CHD deaths in the 35 to 44 age band that year (1.3% of all CHD deaths). Fortunately, Joe doesn’t go on to tell us that we should screen everyone’s cholesterol annually so that we can prevent the heart disease that they won’t have for three more decades. He leaves that to the truly feckless.

    It’s unclear to me why we create entities like PCORI, which, as Dr. Wes correctly notes, is just more government bureaucracy spinning more tales of dubious value, largely in pursuit of more funding, because that’s what bureaucrats do best. Once the money is committed and the tall tales are spun and repeated until they’re gospel, it’s impossible to close down the shop because too many people and organizations then benefit from, and feed off, the narrative, no matter how addled it is.

    And, finally, how can anyone seriously talk about LVADs without discussing theirs costs. The 5-year cost of an LVAD is >$350,000. Like CHD, heart failure is primarily a disease of aging, with 2.5 times as many people over 65 affected as under 65. People of all ages have plenty of options to improve heart health and improve risk factor burden before late middle age. And, I cannot think of a single primoridial prevention (notice I did not say clinical preventive) strategy that requires a wellness vendor or a government agency doing a poor imitation of one.

  15. @joe_selby **the institute will fund large pragmatic studies that focus on direct comparisons of drugs, devices and other forms of prevention, diagnosis and treatment to determine what works best for patients given their individual preferences.***

    Huh? If anyone can understand what he plans to do, please advise. Seems like a colossal waste of money. Besides, the government can not afford to keep people living forever!

    The deaths from heart disease are grossly exaggerated since it is the waste basket (albeit simple) diagnosis for most death certificates.

  16. The comments above of Dr. Wes and Irene K merit close consideration and open debate.

    As for Dr. Wes’ concerns, I would raise a corollary methodological concern. PCORI will be spending over $1billion in the pursuit of a noble goal, but PCORI should feel constrained by the inherent limitations of clinical investigation in general and more particularly by the severe limitations of the approach PCORI is saddled with, Comparative Effectiveness Research (CER). I think it highly likely that this approach will result in information that is of marginal reliability and with little clinically meaningful impact. I explained this concern in 2 posts on THCB in 2010:



    As for Irene K.’s comment, right on. Cardiovascular disease is the commonest labeling for cause of death amongst octogenarians. Of course these are largely the frail elderly who harbor more than one process vying for that label. It’s why I editorialized decades ago that the appropriate diagnosis on the death certificate in this circumstance is “It was her/his time.” I further argue that it is time to modulate the emphasis on disease specific care in the frail elderly (and the not so frail elderly) and substitute a therapeutic contract that considers the quality of the last chapter of life as the therapeutic goal: http://uncpress.unc.edu/books/T-9195.html

  17. Heart disease “remains the leading cause of death in the nation … responsible for one out of every four American deaths.”

    This kind of talk drives me crazy. Age-adjusted mortality from heart disease is at an all-time low, and mortality due to cancer has also been decreasing for years. Just out of curiosity, what would you prefer we die from?

  18. Dr. Selby makes a case for the PCORI without disclosing some important facts for today’s health care consumers.

    First is the $2 fee from every insurance policy sold on the exchange that does to the Patient Centered Outcomes Research Institute (PCORI) created by our new health care law. As I’ve previously pointed out, the costly PCORI replicates functions already performed by the Agency for Health Care Quality and Research (AHRQ). The PCORI’s budget is also scheduled to mushroom from $350 million to over $500 million annually in the years 2014-2019 with patients paying directly for this government agency thanks to this added fee. And what do they get in return from the PCORI? A wealth redistribution scheme to pay for even more “patient-centered” research redundancy.