It was reported yesterday that Pfizer will stop doing research and development in heart disease, anemia and osteoporosis to concentrate in other areas such as cancer, diabetes, and immunology/inflammatory diseases.

This is interesting since Pfizer has (and had) a large number of products in heart disease, including Lipitor, and pharmaceutical companies have typically continued to do research in areas where they have had products because they have established sales people who are knowledgeable about the disease area and have relationships with clinicians in those areas.  The countervailing force is that many effective medicines to treat heart conditions (like high blood pressure and high cholesterol) are available in generic forms and thus the value bar (benefit/cost ratio) that new medicines must reach to be competitive is much higher than when they competing against other non-generic medicines.

However, one common and very expensive heart condition where better medical treatments are needed is heart failure - often called congestive heart failure (CHF).  According the the National Heart Lung and Blood Institute, 5 million Americans have heart failure, and 300,000 die from it each year.  The costs for these patients are very significant: Total costs for treating heart failure in the US are estimated to be $34.8 billion in 2008, and Medicare spent $4.7 billion for hospitalizations related to CHF in 2006.

The chart below from the Centers for Disease Control and Prevention shows the rate of hospitalization (per 1000 people) for heart failure in the US by age group over the years 1979-2004 - clearly a growing problem.

 Hospitalization Rate (per 1000 people) by Age Group for Heart Failure
1979-2004

So what does this mean for better treatments for CHF? According to the pharmaceutical industry’s web site database, there are currently 35 therapies in clinical trials for heart failure or congestive heart failure - including 3 based upon stem cell therapies, 1 based upon cell transplantation, and 1 using gene therapy.  (This compares to the 105 therapies in development for cancer, and 81 for pain.)  So I guess there will continue to be new treatments developed for heart failure, just probably not by Pfizer.  But, recognizing that there are lots of medical problems and limited resources need to be prioritized, will this be OK for current and future patients with heart failure?

Companies allocate and prioritize research and development resources according to three fundamental factors:

1. Unmet Medical Need
2. Scientific Opportunities and Discoveries
3. Market Potential

It is this last one that apparently Pfizer has decided has decreased, so they will be putting their resources into other areas where the combination of all three factors looks more appealing.  As long as all the research-based biopharma companies don’t make those decisions in the same direction (i.e. into and out of the same diseases), then research resources will likely be allocated in a reasonable way to meet societal needs. In that way the needs of people with heart failure will be balanced against those with cancer, chronic pain, diabetes, neurological diseases and immune dysfunctions - which is what society and patients really should want, since people often have multiple diseases or medical problems, so they should want new and better treatments for all of them.

Addendum: The memo from Pfizer’s R&D leadership about their strategic realignment has been posted by Forbes - click here.

Cost containment is becoming an increasingly powerful force in shaping the environment for life sciences companies - as well as other parts of the healthcare system.  In addition, more sophisticated tools for analyzing and demonstrating the clinical and economic value of medical treatments are making it more challenging for life sciences companies to communicate the value of their new products to all types of audiences, including clinicians, payers, patients and regulators.

These new tools and the changing environment are requiring life sciences companies to think about developing more sophisticated messages to reach these audiences. I recently recorded a short 6 minute discussion about these topics with Jeff Sandman, CEO of Hyde Park Communications - where I am also a Senior Counselor.  Click on the icon-link below to listen to our discussion.

And as always - if you have any comments on this topic - please feel free to share them.

An article in the July/August Health Affairs about Massachusetts health plans implementing Pay-for-Performance (P4P) incentives for physicians raised more questions than it answered.

The study found that P4P programs from 5 private sector payers “wasn’t associated with greater improvement in quality” compared to the overall upward trend in the factors measured.  But the study didn’t address some overarching questions and basic realities about P4P, such as:

• How the payers P4P incentives to the physician groups was actually translated into incentives for the individual physicians - or smaller groups of physicians inside the larger groups?
• How the P4P incentives compared to the other financial incentives the physicians are facing?  For example, seeing more patients or doing more procedures could increase their income more than meeting the P4P standards. (The Health Affairs article states that P4P incentives for Massachusetts physician groups averaged 2.2% of their income.)
• The quality measures used in the study were all performance based, rather than actual outcomes, e.g. cholesterol screening rates rather than patients’ actual cholesterol levels, HbA1C screening rates in diabetics rather than their actual HbA1C levels, or asthma medication use for children ages 5-17, rather than ER visits or hospitalizations for these same children.  What impact does that has on physicians’ behavior, and the value of changing their actions to meet these process standards?  Would physicians be more responsive to incentives tied to clinical outcomes?

Making Incentive Programs Successful:
While the study concluded that the P4P incentives program instituted in 2002 may not have produced dramatic changes in the HEDIS process measures, that does not mean  they were ineffective or that P4P is not a useful tool.

First, while collecting process measures data is easier, since clinical outcomes are what patients (and their physicians) should really care about, shouldn’t P4P incentives be based upon actual clinical outcomes? Process measures are easier to monitor by using billing data, but as the prevalence of quality electronic medical records systems grows, collecting and analyzing data about clinical outcomes will become much easier.  In addition, measuring a small set of any factors – process or outcome – presents the pitfall of driving physicians to focus on those diseases and measures to the exclusion of other important things.  For example, in the Health Affairs study, there are a number of preventive services in the process measures, but what about flu vaccinations, colonoscopies or smoking cessation?  This “managing what is being measured” behavior is why the number of factors used for P4P incentives should be as broad as possible.  (But this does not mean that they all have to be measured at every interval, or for every compensation period.)

Second, as any psychologist (or parent) will attest, the time between the actions and the reward (or penalty) is very important for changing behaviors. The Health Affairs article indicates that the bonuses are paid to the physicians groups annually.  Having the incentives paid annually, (or even quarterly), would be unlikely to provide adequate feedback to physicians to prompt them to change their behaviors.  An alternative blended methodology would be to provide physicians feedback on their actual performance against many of the possible measures on a weekly or bi-weekly basis, while making the P4P payments on a monthly or quarterly basis.

Third, many large companies structure their bonuses for their senior managers around a minimum of 20% of compensation.  If incentives for P4P programs only represent a small percentage of physicians’ income, then it would be unlikely to change their behaviors – particularly if they can make up for any lost income by increasing volume.  However, if physicians are being paid a fixed (capitated) amount per month to provide a certain set of services to a patient group – either primary or specialty care – then the volume part of the equation disappears, and P4P programs could be much more effective, even at a lower fraction of their potential income.

And lastly, and most simply, the insurers would not be spending time and money developing and implementing these programs if they didn’t think they provided some benefit – even if it is only financial - so they must be getting some benefits, or at least learning some things to make these programs beneficial in the future.

Conclusions:
18 years ago I wrote a book chapter that focused on structuring incentives for physicians.  Since then it has been hard to move payers and clinicians toward using more focused financial incentive systems.  But the P4P concepts are important, and to be successful they need to be implemented in a way that works for payers, physicians, and patients.  Unless these and other stakeholder groups buy-in to the purpose and practice of such incentives systems, they are unlikely to have the desired effects.  And the result will be more of the same – rising costs, variable quality, and limited access for many patients.

Medical information can change how clinicians treat patients, how patients care for themselves, and how healthcare payers promote or prevent the use of treatments and diagnostic tests. However, this information can act as either a broad sword or a scalpel, and produce good or bad outcomes.

A recent report from a Canadian new service about an article from the Canadian Medical Association Journal describing the outcomes from warning about the use of anti-depressants in children brings this issue down from a general concept to being very specific. This news report stated:

Two years after Health Canada warned about prescribing anti-depressants to children, the number of children and teens who died by suicide increased 25 per cent after years of steady decline, major new Canadian research shows.

And the increased suicide rate coincided with a 10-per-cent decrease in the rate of visits to doctors for the treatment of depression in children.

For the study, researchers tracked what happened in Manitoba before and after Health Canada warned in 2004 that newer antidepressants may be associated with an increased risk of “suicide-related” events in patients under 18.

They found the warning was followed by an overall 14-per-cent drop in antidepressant use among children and adolescents, fewer visits to doctors for depression, and - among eight- to 17-year-olds - increased rates of completed suicide.

More than 90 per cent of the children and teens who killed themselves were not taking antidepressants when they died.

Published Tuesday in the journal of the Canadian Medical Association Journal, the study is the first to document “such a wide range of unintended health consequences” from a major drug warning, the authors say.

Lead author Dr. Laurence Katz, a child and adolescent psychiatrist in Winnipeg, warns the increased risk of suicide could be a “random fluctuation.”

“We can’t say the warning, or the change in antidepressant use or the physician office visits caused changes in suicide rates,” says Katz.

The suicide rate among children and teens was also still relatively small, from 0.04 for every 1,000 children and adolescents before the warning, to 0.15 per 1,000 after.

But Katz worries the widely publicized drug warnings have led to more cases of untreated depression, and an impact “beyond what was intended.” The drop in doctors visits for depression suggests that some vulnerable children are getting no treatment, including psychotherapy, at all. He says his hunch is that families were afraid to go to the doctor for fear their child would be put on medication.

“But that’s not the only treatment for depression. Not going to the doctor deprives you of all forms of treatment.”

If anything, researchers expected office visits to go up after the warning was issued because physicians were urged to increase the monitoring of patients for potential adverse reactions.

Katz, an associate professor of psychiatry at the University of Manitoba, says the drug warnings and media response may have “generated a lot of fear.”

“Understandably parents who kept bringing their children, their teenagers in for troubles with depression were already struggling, and fearful (and) often appropriately cautious about whether their child or teenager should be put on a medication.”

Katz believes the findings could be applied to any Canadian jurisdiction. Other studies coming out of the U.S. are showing similar results. [Emphasis added]

The antidepressant warning involved drugs known as SSRIs, or selective serotonin re-uptake inhibitors, a class that includes Prozac, Paxil and Zoloft, as well as serotonin noradrenaline re-uptake inhibitors (SNRIs), which include Effexor. The drugs have not been approved in Canada for children, but doctors have prescribed them “off-label,” which they are legally permitted to do, to tens of thousands of toddlers, children and teens for depression, social phobia, anxiety and obsessive-compulsive disorders.

In 2003 the U.K. banned antidepressants for children. The only exception was Prozac. Studies have shown the drug is safe and effective in children.

A year later, Health Canada warned that people taking the newer-generation antidepressants may experience behaviour or emotional changes that may put them “at increased risk of self-harm or harm to others.”

Katz says he didn’t have a problem with the warnings themselves. But he says some people leaped to the assumption “that these medications lead people to kill themselves.”

[The report also notes that, “For young adults, there was no significant change in the rate of completed suicide.”]

Obviously, the outcomes found in this study are very worrisome, but it also a too dramatic example of the principle of unintended consequences.

It also reminds me of how a news story in the early 1990s about adverse reactions with the second medicine to treat AIDS.  This news report caused many AIDS patients to stop taking the medicine, and given that there was only one other medicine to treat AIDS, this certainly wasn’t a good thing for their long-term survival

Although correlations don’t prove causations, I think this study definitely underscores the importance of healthcare regulators - and their media colleagues - carefully considering how they present new health information and notices to the public - for both good findings or dire warnings. With all the proposals to empower patients to make their own decisions through consumer directed insurance plan, and to give people more health information, there should also be much more research into how people respond to health related information delivered in different forms from various sources.

The National Federation of Independent Businesses (NFIB), just launched their health reform campaign called Solutions Start Here. Their 10 small business principles for healthcare reform includes:

Evidence-based:
The healthcare system must encourage consumers and providers to accumulate evidence and to use that evidence to improve health. Appropriate treatment choices and better wellness and preventive care should be key outcomes.

Current information and decision systems make it difficult to accumulate, interpret and use evidence affecting treatment decisions. One result is overspending on treatments and underspending on prevention. Decision-makers must understand the impact of their decisions on both costs and outcomes. Such an understanding must be based on solid clinical and economic evidence.

(The NFIB’s other 9 reform principles are Universal, Private, Affordable, Unbiased, Competitive, Portable, Transparent, Efficient, and Realistic.)

As I’ve said before, evidence-based medicine is great in theory, but like a lot of good theories, it can go sour in practice. Thinking about the NFIB’s membership and how they might do business based upon evidence-based value of their products and services, selling undercoating for automobiles came to mind. I’ve been told that buying this dealer sprayed on stuff (versus what’s applied at the factory before the car gets trucked hundreds or thousands of miles to you) is a waste of money - and of course getting undercoating applied to used cars makes even less sense.

Applying evidence-based standards to many products and services would be great, but it could also drive many small businesses into bankruptcy - because either the evidence shows there is no value, or the business isn’t big enough to pay for the research to generate the evidence. Of course I realize that healthcare companies are generally not small businesses, but the same principles of investing scarce resources should apply - What goals are we trying to achieve (improve quality? control costs?); How much are we going to invest in a particularly project or problem area (both dollars and experts’ time that can only be used once); What are the expected returns towards our goals from those investments, and how are we going to measure that progress? Many of these questions seem to remain unanswered in the healthcare debate, and in the push for more “evidence-based” medicine.

Any other thoughts on EBM?

In a previous post I was somewhat critical of evidence-based medicine (EBM) when it is used to make payment decisions. One of the points I was trying to make is that EBM is not a passing fad. The staying power of EBM was recently reinforced by two recent developments.

First, the Medicare Payment Advisory Commission’s (MedPAC) March 2008 Report to Congress cites their own 2005 report recommending EBM as a touchstone for comparing physicians’ practices as one way to improve quality of care and value for the Medicare program:

In the March 2005 Report to the Congress, the Commission recommended that CMS measure physicians’ resource use over time and share the results with physicians (MedPAC 2005). Physicians would then be able to assess their practice styles, evaluate whether they tend to use more resources than their peers or what evidence-based research (when available) recommends, and revise their practice styles as appropriate.(13) Moreover, when physicians are able to use this information in tandem with information on their quality of care, they will have a foundation for improving the value of care beneficiaries receive.

Private insurers increasingly measure resource use to contain costs and improve quality (MedPAC 2004b).(14) Evidence on measuring the effectiveness of resource use in containing private sector costs is mixed and varies depending on how the results are used. Providing feedback on use patterns to physicians alone has been shown to have a statistically significant, but small, downward effect on resource use (Balas et al. 1996, Schoenbaum and Murray 1992), but, when paired with additional incentives, the effect on physician behavior can be considerably larger (Eisenberg 2002).

This report also notes that dialysis care is one area most ready to make use of EBM for payment purposes:

The dialysis sector is ready for pay for performance: Evidence-based measures are available, providers can improve on these measures, data are available to risk-adjust the measures, and systems are available to collect the information. CMS already collects some clinical information—dialysis adequacy and anemia status—on providers’ claims. CMS is developing additional data infrastructure that will permit the agency to collect information about quality of care from all facilities.

Any nephrologists our their have any thoughts about this?

The second new development related to EBM is the launch of “the updated, expanded, and searchable Tufts Medical Center Cost-Effectiveness Analysis (CEA) Registry website.” According to an email from the Peter Neumann, the Director of the Center for the Evaluation of Value and Risk in Health at the Institute for Clinical Research and Health Policy Studies at Tufts Medical Center, (Peter - get a shorter title), this registry “provides public access to a comprehensive online database of cost-effectiveness ratios from the published medical literature.” And has the “mission is to identify society’s best opportunities for targeting resources to save lives and improve health and to help standardize cost-effectiveness methodology.”

What distinguishes the CEA registry from the proposal to create a Center for EBM that MedPAC made in February, is that the registry is a resource for understanding the “evidence” part of EBM without any direct ties to using this information for changing payments. A colleague recently agreed with my off-line assessment that one of the challenges is that EBM - and its cousin pay-4-performance - are almost always directed at clinical areas where there is believed to be costly overuse or misuse. Very rarely are these same potentially quality improving tools directed towards clinical situations where there is documented underuse - situations where quality could be improved, long-term cost savings achieved, but there also might be short-term cost increases. This is one of my touchstone secrets for evaluating the intentions of “quality improving” initiatives - do they target any practices where there is documented underuse?

And one other interesting observation about the CEA registry. It classifies its information into 4 categories depending upon the conclusion of the research:

1. Increases Costs/Improves Health
2. Increases Costs/Worsens Health
3. Decreases Costs/Worsens Health
4. Decreases Costs/Improves Health

Doing a quick assessment of the registry revealed an interesting landscape: There are about 27 more sources for #2 than there are for #3. (Types #1 and #4 are midway between, with 8 and 10 times as many pieces of information as #3.)

There could be several possible reasons for this lopsided distribution: There really could be a LOT more clinical practices that waste money and worsen health. Or this could be the area that healthcare payers will pay for research to be conducted. Or researchers know that these types of findings will bring more research funding from payers.

I believe that the second of these scenarios is the most likely since payers are primarily concerned about reducing care that increases costs and worsens health. However, I also believe that these ratios don’t reflect the full picture of clinical care, and that there are many clinical practices that if used more would improve health - whether they increase or decrease costs….. of course that calculation often depends upon what time-frame and scope of society is considered, which leads back to the old question “costs to whom?”

What do you think?

The US Medicare Payment Advisory Commission (MedPAC) recently released a report on “Creating a Center for Evidence-Based Medicine” that was prepared by an outside analysis group. Before dissecting the MedPAC report, let me just lay out some of the more controversial aspects of evidence-based medicine (EBM):

• How are the results of EBM research used for coverage or payment?
• Are the EBM conclusions based upon reviews of prior studies or on research done specifically for the EBM analyses?
• Are the EBM conclusions relevant only for a clinical research situation, or do they reflect real-world practices?
• All medical practices evolve and “best medical practices” are reflected last in textbooks….. after they appear in journals….. after they have been presented at meetings….. after research has been done to understand these practices. How do EBM analyses account for this timeliness factor and include the latest advances?
• How does the EBM analytical process question the validity of its own assumptions - particularly the perceived benefit by patients, or calculations about the “value” of the outcomes from a treatment?
• And related to the previous question - Do the EBM analyses reflect only the benefits to the individual patient or spending by the health plan, or do they include benefits to other parts of society, i.e. families, employers, etc.

Overall, the question is, how does EBM research translate information about the outcomes produced by various medical treatments into better medical practices? When I was in medical school, this was the purpose of textbooks and professors. If national (or global) EBM organizations can accelerate this process and make it more accessible (possibly using new information technologies), then that’s probably fine. But if its functions are subordinate to the cost reduction agendas of healthcare payers, (and this leads to rationing of healthcare services and products based more upon cost than real value - which has been the case with virtually all existing EBM organizations), then a US Center for EBM will become another part of our healthcare system’s problems rather than a step towards solving them.

Below is some commentary on the MedPAC report and some of the existing EBM organizations it discusses:

The MedPAC report outlines several layers of functions for the proposed Center for EBM:

1. Practice Identification and Review
2. Dissemination (of information and conclusions)
3. Training and Technical Assistance
4. Practice Adoption (via education and working with stakeholders)
5. Clinical Outcome Review

Clearly #4 is the key to making EBM research findings useful, and the report cites three critical issue for the voluntary adoption of practices found to be beneficial via EBM research:

1. Credibility
2. Stakeholder Involvement
3. Viable Economic Incentives

Of these, #3 is the most contentious, and the report notes that, “Since economic incentives often represent a threat to opponents of creating a centralized organization of the type described here, it may be desirable to leave that implementation to policy makers rather than treating it as the role of the organization.”

As noted above, a major controversy about “Evidence-Based Medicine” (EBM) is how it is used to make coverage and reimbursement decisions. The report recommends that EBM research and these decisions be kept separate, but the experience with EBM organizations in other countries, and in US health programs like Medicaid and the VA, has been that this is often not followed in practice. On one end is the Department of Veterans Affairs Medical Advisory Panel (MAP) which - as part of the VA’a National Formulary development process - is tasked with performing evidence-based reviews of therapeutic drug classes “that may or may not lead to national standardization contract initiatives.” While this sounds like a rationale and analytical process, my experience with this process is that the MAP does analyses to justify the inclusion of the least expensive medicines on the VA’s formulary.

Because the VA is only about 5% of the US healthcare market, it doesn’t have a sweeping impact on medical care in the US. However, it often goes on the record saying that its methodologies should be adopted by Medicare and private insurers - something that would have much greater implications.

The MedPAC report also talks extensively about the National Institute for Health and Clinical Excellence (NICE). This is one of the most studied EBM-type organizations. While unlike the VA’s MAP, NICE is not technically part of the UK’s National Health Service (NHS), it is created and funded by the British government - so just as two brothers are not the same person, they receive their allowance from the same parents. While the MedPAC report generally praises NICE, the real world experience of patients and companies is somewhat different, and in the global discussion of healthcare policy and economics, it is often cited as a classic fourth hurdle for accessing treatments, i.e. it has become the NHS’s de facto rationing resource.

And one final note of concern. In a previous post, I discussed the very low attendance at a session on Comparative Effectiveness (a type of EBM research) at the annual meeting of the American Association for the Advancement of Science (AAAS). If at a meeting with thousands of researchers, almost none were interested in this topic, what does that portend for the ability of a national EBM organization to conduct independent and analytically driven research without undue political and financial influences?

Have you seen payers pushing clinical practice recommendations under the guise of EBM when they were clearly financially driven initiatives to limit access to certain treatments (a.k.a. rationing), and would produce lower quality care for patients or just chew up the clinician’s time trying to navigate the additional barrier to getting the best care for patients?

What are your thoughts?

I attended the annual meeting of the American Association for the Advancement of Science today to hear a session titled “Health Economic Evaluations of Medical Technologies: Is the Cost Worth the Cure?”  The topic of this session was really about comparative effectiveness of medical interventions - particularly pharmaceuticals. The panel was a substantial group of physicians and health services researchers/regulators:

• Milton C. Weinstein, Harvard School of Public Health
• Michael F. Drummond, University of York, United Kingdom & NICE (National Institute for Health and Clinical Excellence)
• Jeffrey Kelman, Chief Medical Officer at CMS
• Marc Berger, Eli Lilly
• Tracy A. Lieu, Harvard Medical School and Harvard Pilgrim Health Care

The most impressive thing about this 3 hour session was that at a meeting with thousands of attendees, there were 12-15 people in this session.  Clearly the organizers had expected more, since the room had space for a couple of hundred.

Despite the small audience, the panel gave interesting - if not too in-depth -  presentations which at times delved into jargon about programs such as Medicare Part D, and unfortunately didn’t engage in speculation about the future of comparative effectiveness for decision making about the allocation of resources for healthcare services or research.

What was clear, is that (as I mentioned in an earlier post), comparative effectiveness is something here to stay.  The question remains to see how it will be used in the future by payers (particularly in the US), and how this will effect the quality of care, and the direction and intensity of research activities.

Peter Orszag, the Director of the Congressional Budget Office (CBO), recently testified before the Senate Budget Committee about increasing health care costs. One of his conclusions was that “the most important factor driving the long-term growth of health care costs has been the emergence, adoption, and widespread diffusion of new medical technologies and services by the U.S. health care system.”

His testimony concludes that by using “comparative effectiveness” research to “generate more information about the relative effectiveness of medical treatments and changing the incentives for providers and consumers,” would create a situation where “savings are possible without a substantial loss of clinical value.”

While this all sounds good in principle, the challenge obviously is to make the information useful, reliable and accessible. And, of course, as the testimony notes, “To affect medical treatment and reduce health care spending, the result of comparative effectiveness analyses would ultimately have to change the behavior of doctors and patients — that is, to get them to use fewer services or less intensive and less expensive services…”

CBO has been greatly increased their health care staff, created a Panel of Health Advisers last fall, and the comparative effectiveness issue was not a tossed-in part of the CBO testimony — CBO had a separate report on this topic last fall, and Director Orszag will be part of a panel on the topic at the Institute of Medicine on February 21st.

Comparative effectiveness seems to be the latest in a series of attempts at transforming health care operations in the US that can be traced back several decades, and includes: Consumer Directed Health Plans, Managed Competition, and Managed Care - particularly HMOs.

The question is, will comparative effectiveness really change clinical practice to alter the course of expected increases in health care spending without sacrificing quality?

What do you think?