Piece of Mind

Hierarchies of Evidence for Comparative Effectiveness - Reinforced by Unequal Quality of Publications?

2011-05-26T18:15:00.000-07:00

Image via WikipediaThe ISPOR Annual International Meeting in Baltimore this week was dominated by workshops and sessions addressing comparative effectiveness research (CER) and implications for US health policy. I moderated an issue panel addressing whether experimental or observational studies should have a higher rank in healthcare decisions. We were finished addressing the trade-offs between the internal validity of experimental studies and external validity of observational studies when an audience member commented on the high prevalence of low quality observational studies in the scientific literature. This moved the panel to an important topic that's not commonly discussed.

While observational research methods have evolved, the quality of observational data has not. We still throw very complex and sophisticated statistical models at very crude administrative data. Even worse, we make only cursory mention of the limitations of such datasets in our scientific papers. In short, the quality of many studies is either poor or the description of such studies is not transparent. There is a consensus statement that establishes standards for transparency and reporting of observational studies - the STROBE Statement (STrengthening Reporting of OBservational studies in Epidemiology). Unfortunately, many papers lack the transparency necessary to evaluate study quality.

Clinical trials have a reporting standard through the CONSORT Statement, which was developed in the early 1990's. Currently no decent medical journal will publish and results of a randomized controlled trial that does not adhere to CONSORT standards of transparency. The STROBE Statement was published in 2007 and hopefully will soon become a universal standard for all credible medical journals. Until the reporting of observational studies rivals the transparency of RCTs in the scientific literature, RCTs may continue to be granted higher status even when they are not the appropriate means of answering the question at hand.

#Adversity, #Resilience, and #Leadership

2011-04-23T08:23:00.000-07:00

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Nearly all men can stand adversity, but if you want to test a man's character, give him power.: Abraham Lincoln

I came across this quote in my Twitter feed and immediately wondered whether in fact most people can handle adversity, particularly in leadership settings. I'm not aware of the context of this quotation, but Lincoln appears to be stating that how one behaves when possessing power reveals their true character. Others are less likely to hold a powerful individual accountable, so his or her internal checks and balances are the only buffer to avert abuses. This is fairly self-evident and consistent with other commentaries on the Web.

On the other hand, adversity is also a test of character if we differentiate between those who endure it and those who master it. Resilience is the capacity to "bounce back" from adversity and has been studied in the context of PTSD among Gulf veterans, survivors of natural disasters, and displaced workers.

Those who only thrive under ideal circumstances are ill-suited for leadership roles in an increasingly unstable and tumultuous world. Moreover, failing under adversity is not the kiss of death. If one succeeds in delivering results and even thriving when times are hard, great. If one fails under adverse circumstances, the key is how they deal with the consequences. Scanning the web on keys to resilience, there are several common themes:

Develop and maintain caring relationships for support, advice, and companionship
Cultivate optimistic self-confidence that is only mildly exaggerated
Be playful, curious, and child-like
Develop a clear sense of purpose and personal mission

Maybe Lincoln found that growing up on the American frontier these traits were common. Today they are increasingly rare, but those who develop these will thrive under adversity and use power effectively.

Confounding By Indication and Comparative Effectiveness

2011-02-21T15:57:00.000-08:00

Image via WikipediaOne of the major criticisms of observational research is "confounding by indication", also referred to as "treatment selection bias". A confounder is a factor associated with both exposure (treatment) and outcome without being part of the causal pathway. Because selection of treatments is not random and is determined by patient and physician characteristics, the observed effect is influenced by factors other than the treatment. It may not be possible to fully adjust for the effects of such confounding and one therefore doesn't know the "true" treatment effect without some additional work. A simple example is intravenous versus oral antibiotics in hospitalized patients. Patients receiving IV antibiotics are usually sicker than those receiving oral antibiotics,so we expect the former to have a higher unadjusted mortality rate. Once we control for disease severity and other confounders that determine who receives IV vs. oral antibiotics, we have a more accurate assessment of the relative effects of each treatment on hospital mortality.

Confounding is one of the reasons that randomized controlled trials are considered by many to be the gold standard for answering questions of comparative effectiveness. Randomization under double blind conditions prevents physicians from choosing treatments. With a large enough study sample, randomization ensures that each treatment group is essentially identical, so any differences in outcome may be attributed solely due to the treatments. However, in clinical practice physicians and patients may choose a medication of lower proven efficacy because it may be more acceptable for reasons specific to them. Under such circumstances, a more efficacious medication that loses all effect after 1-2 missed doses may be less attractive than a less efficacious medication that has a good effect even with low adherence. In an observational study, we may find that both medications are equally effective in clinical practice even if one is superior in a clinical trial. At this point we can either throw out the observational result as invalid and require patients to be perfectly adherent, or acknowledge that assessing comparative effectiveness is complicated.

As scientists and policy makers continue to debate levels of scientific evidence, the obsession with determining which treatment is "really" better seems a little naive. Few patients and physicians have the resources to ensure replicate clinical trial monitoring, treatment adherence, and clinical outcomes in daily practice. They are constantly forced to make choices based on limited evidence and resources, and are guided by personal values, none of which can be "controlled" to determine the "real" treatment effect.

In the debate between observational and experimental research design it is important to remember that another term for "treatment selection bias" and "confounding by indication" is clinical judgment. Trying to "adjust" judgment out of all analyses seems neither credible nor desirable in a world of imperfect knowledge and people.

Comparative Effectiveness - The Answer Depends on the Question

2011-01-16T14:14:00.000-08:00

Image via WikipediaOne of the key challenges in Comparative Effectiveness Research (CER) is synthesizing evidence from multiple studies with varying designs to arrive at an estimate of a treatment's overall effectiveness. This is the process of health technology assessment (HTA). Systematic reviews are one means of accomplishing this and may lead to a full meta-analysis or mixed treatment comparison (MTC), a statistical model that uses head to head and placebo-controlled trials to estimate the relative efficacy of multiple treatments (sort of a Fantasy Football for healthcare treatments).

Systematic reviews are the core of HTAs and start with a specific question of interest to the reviewer. A standard approach to all research questions is PICO, or "Patient, Intervention, Comparison, and Outcome". By pre-specifying the patient population, intervention(s), comparator(s), and outcome(s) of interest, a search strategy can be developed and implemented in any of the available literature search engines. For example, "Among cigarette smokers without co-morbid substance abuse or psychiatric illness (P), how does nicotine replacement (I) compare to cognitive behavioral therapy and 12-step programs (C) in achieving one-year tobacco abstinence and with respect to medical and psychiatric complications (O)?" This question may then be refined to develop search terms to collect abstracts and manuscripts.

A systematic review then requires a framework for evaluating the quality of the studies, including those that are informative and excluding those that are not. The pre-specified search may involve inclusion and exclusion criteria based on a minimum sample size, randomization (for trials), and other design issues. However, the resulting studies must be evaluated to rate the quality of evidence of each study. The US Preventative Services Task Force (USPSTF) uses a hierarchy of study design as the starting and ending point for rating studies. Properly conducted randomized controlled trials (RCTs) receive Class I designation as the highest quality evidence while non-randomized trials or cohort studies receive Class II designation. Case series and expert consensus receive Class III designation. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group employs a somewhat different approach to apply designations of High, Fair, and Poor quality. Study design still dominates, with RCTs "starting" as High and observational studies Low quality. However, a criteria-driven process may downgrade RCTs or upgrade observational studies. Any study with a "fatal flaw" is designated as Poor quality. Both of these approaches are based on the assumption that the internal validity offered by double blind randomization is the most important element in any question related to comparative effectiveness.

The Agency for Healthcare Research and Quality (AHRQ) takes a somewhat different stance in its Methods Guide for Comparative Effectiveness Reviews. While acknowledging the inherent strength of RCTs to robustly answer questions of efficacy, the authors note that the strength of the design is only assessed in the context of the question at hand. Specifically, they cite that the long-term safety of a new medication may best be assessed through an observational study. Why? Because RCTs tend to attract healthier patients without many of the co-morbidities and concomitant treatments that may affect the overall safety of the medication. In other words, RCTs may have biased enrollment that prevents them from answering the question of real-world safety outside of controlled experimental settings.

I would extend this caveat to any questions of real-world effectiveness of treatments to achieve desired clinical outcomes in non-experimental settings. For example, if physicians do not commonly prescribe the same dose studied in published RCTs or in the product label, systematic reviews that favor such studies may be irrelevant to the question of comparative effectiveness in current practice. In one study, colleagues and I demonstrated that time to psychiatric hospitalization was longer with one antipsychotic compared to others. This appears to have been influenced by the fact all of the medications tended to be initiated at sub-therapeutic doses. The comparators tended to be dosed much lower that the intervention of interest. A systematic review and meta-analysis of the RCT literature would have found no meaningful difference between treatments. In real world practice, there was.

The experimental design of RCTs is our gold standard for determining whether a medication has sufficient biological activity to favorably affect disease. Robust methods for comparing such effect sizes across different trials are available. However, policy makers should be cautious in assuming that experimental results can be directly applied to current clinical practice. If our question relates to real-world practice settings, observational methods may be the most appropriate design to answer the question.

New Year's Resolutions for US Healthcare

2011-01-01T09:45:00.000-08:00

Image via WikipediaThe ball has dropped, the ACA is law and, despite challenges on both sides of the aisle, the implications of health reform are emerging. These are a few of the long overdue promises the US healthcare system is making to us.

1. Expanded health insurance coverage While the promise is coverage for all citizens, it seems that high risk pools are being underutilized and the individual tax penalties for non-coverage are being challenged in court. However, broader Medicaid eligibility criteria will certainly enable more people to enroll in this safety net health insurance program.

2. Commitment to healthcare quality
Accountable care organizations (ACOs) are a key element of the ACA, driving provider/hospital alignment and managing incentives to increase the practice efficient, effective medicine. The "Quality Chasm" described by the Institute of Medicine in 2001called for a radical redesign of healthcare processes and incentives to ensure that practice patterns are consistent with the best scientific evidence. Only a decade later and we're finally on our way.

3. Evidence-based medical practice
The Patient-Centered Outcomes Research Institute (PCORI) owns the challenge of prioritizing and defining the process for evaluating the effectiveness of different healthcare interventions. Comparative Effectiveness Research (CER) is the process of evaluating various alternatives, including watchful waiting, and assessing the relative benefits and risks. The goal of CER is to provide actionable information to patients, providers, payers, and policy makers that lead to effective, informed, real world decisions. This goes far beyond reviewing randomized controlled trials, which have limited applicability to most clinical practice. A key challenge of the PCORI Methodology Committee will be to create a framework for integrating evidence from a variety of study types, and to inform the PCORI on the suitability of specific study designs to answer specific questions.

4. Managing healthcare spending
There is broad agreement that current healthcare spending trends are unsustainable. Moreover, the Dartmouth Atlas provides disturbing evidence that higher spending is not associated with better outcomes. Rather than promoting radical spending cuts and arbitrary restrictions on access to treatments, the ACA, through PCORI and ACOs, aims to squeeze unnecessary, ineffective, and harmful costs out of the system. Of course, this requires significant up front investment to develop the systems, processes, evidence, and competencies to ensure that healthcare dollars are spent wisely. The European focus on cost-effectiveness of individual interventions relies heavily on trial-based evidence generated under near-ideal conditions, i.e. the patient is clearly diagnosed, has few co-morbidities, is motivated for treatment, and selected based on the best potential to respond. Economic analyses of care processes, quality improvement, and other systemic changes are likely to generate greater cost savings than managing access to individual interventions.

These New Year's resolutions are not those of the US government, the AMA, or state health authorities. They are commitments for all of us who claim to have an interest in affordable, timely, effective healthcare that extends and enhances human life. We may not agree with every provision of the Affordable Care Act, but it does challenge us to join forces to tackle these longstanding problems in US healthcare with rigor and discipline.

Comparative Effectiveness Research - The Devil in the Details

2010-12-05T09:37:00.000-08:00

Image via WikipediaIn the October issue of Health Affairs we find a rich discussion on the challenges faced by the Patient Centered Outcomes Research Institute (PCORI). The issue also clarifies the need for the PCORI Methodology Committee to develop a new, flexible framework for compiling and evaluating evidence for healthcare decision makers.

In a paper by Louis Garrison et al, comparative effectiveness research (CER) compares two or more alternative interventions (placebo is not necessarily an alternative); focuses on real world outcomes, i.e. hospitalization, healthcare costs, productivity; and is intended to inform a wide range of decision makers - patients, physicians, hospitals, and payers rather than simply the FDA. Each of these decision makers has a different set of priorities and perspectives, which makes the conversation so difficult.

Patients and providers want access to new treatments because existing therapies have limitations. Simply put, there is always unmet medical need. Payers, hospitals and other purchasers want to ensure that treatments provide meaningful clinical and economic value relative to the costs incurred. There is wide consensus that the current trend in escalating US healthcare costs is simply not sustainable. The challenge is how to manage those costs without "splitting the baby", i.e. cost cutting that potentially harms patients and generates new costs resulting from those harms.

Potential harms incurred by the misapplication of CER data were described by the article by David Shern et al using schizophrenia as an example. A "null finding" in a large clinical trial involving multiple treatments and high patient variability (the epitome of the "pragmatic clinical trial") does not mean that the treatments are all interchangeable for all patients. Rather, these results invite exploration of sub-groups that may have differentially better or worse outcomes to different treatments. The Affordable Care Act's (ACA) language on PCORI's CER mandate specifically addresses the need to study how different sub-populations may have better or worse efficacy and/or safety to different treatments.

As the PCORI Methodology Committee is appointed and begins their work, it's encouraging to know that there is already a very robust and public discussion in the scientific literature. This is a highly beneficial preliminary result of the ACA, and should help the general public see beyond the rhetoric. Informed debate will yield the best results for all stakeholders.

Comparative Effectiveness - In the Eye of the Beholder?

2010-07-01T18:32:00.000-07:00

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I had the pleasure of attending a conference, "Shaping Convergent Strategies in Comparative Effectiveness Research" last week to hear who's who group of speakers discuss the implications of the Patient Protection and Affordable Care Act (PPACA), also known as "Health Reform". The conference was covered by the press and summarized nicely by the National Pharmaceutical Council, one of the co-sponsors, on their website. In a nutshell, the Patient-Centered Outcomes Research Institute (PCORI) has the daunting task of shaping a process for defining the levels of evidence necessary to render informed decisions regarding the relative merits of treatment options.

While many academicians and policy makers feel that the only logical approach is a meta-analysis of multiple randomized controlled trials, observational studies that reflect the actual process of care delivered may be equally informative. If nothing else, it helps identify issues in the quality of health delivery that also contribute to costs. The challenge is that, in the current hierarchy of scientific evidence, clinical trials are virtually always deemed superior to even well-designed observational studies. Precisely how the relative merits of different studies will be weighted and pooled for analysis is unknown. Even more complex is how FDA and CMS will address evidence standards for marketing approval (FDA) and reimbursement (CMS).

The phrase "May you live in interesting times" is supposedly a Chinese curse. These are indeed "interesting" for everyone - policy makers, payers, healthcare professionals, regulatory agencies, and, most importantly patients. However, I feel honored to be part of such historic events.

Comparative Effectiveness vs. Cost Effectiveness Research

2010-05-23T16:35:00.001-07:00

I recently attended the annual meeting of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) in Atlanta. As always, it was an opportunity to brush up on methodology, catch up with friends, and check the pulse of our field. The best part of the meeting is that, though we may work for rival companies, there are no "competitors" - only colleagues and friends. Our community is too small and mobile to be caught up in the juvenile rivalries pharma companies demonstrate at clinical congresses. In December at a major hematology congress all 100 reprints of a poster I was presenting vanished before the session even began. Either there was enormous interest in an insurance claims study or someone became a little over-zealous in "defending" their brand.

The buzz at ISPOR was all about Comparative Effectiveness Research (CER) and the new US health reform bill. One ongoing theme was the evidence necessary to conduct CER. Randomized controlled trials are often seen as the "gold standard" in determining causality, but such studies rarely replicate the clinical settings, doses, and combinations in which medications are actually prescribed. Even the patients tend to be different. This is a longstanding debate - are observational studies as "good" as clinical trials? In the end it depends on how we define "effectiveness".

I also noted a lot of obsessional interpretation of the health reform bill language that prohibits the newly chartered Patient Centered Outcomes Research Institute (PCORI) from using "quality-adjusted life years" (QALYs) as a measure of cost-effectiveness. Some academics interpreted that to mean that cost-effectiveness was still fair game, but only QALYs were off the table. One problem is that cost-effectiveness analysis (CEA) can be misapplied to large populations based on limited data from smaller clinical trials. Moreover, there is little evidence to support the generalizability of trial-based CEAs to the health system at large, just as rigid clinical trials are often not generalizable to clinical practice.

A rush to judgment may lead to sweeping generalizations that leave out people who don't fit under the bell curve. Unfortunately we've avoided the difficult questions for so long that political and economic pressures make short-sighted interventions tempting.

Reflections of a father

2010-02-13T08:14:00.000-08:00

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Last night I had the pleasure of taking my three daughters to the school's Daddy-Daughter Sweetheart Dance. Since the twins are in kindergarten and my oldest is in fifth grade, it was the only time all three would be at the same dance. With hundreds of K-5 girls decked out and an army of volunteer mothers to ensure that the girls had a great time despite us dads, it was a rare and overwhelming (for me) event.

I danced with the girls when they wanted to, stayed out of their way when it seemed appropriate. My oldest, a deep thinker who recognized the uniqueness of this event and anticipating the impending challenges of adolescence, told me she didn't want to grow up. Meanwhile the twins were darting in and out of the gym, confident of their surroundings and vigilant mothers as they explored their emerging independence. Moreover, their classmates and those of my oldest were also watching out for them.

Thinking about the messy state of healthcare in the US, it's strange to realize that corporate and government leaders who are currently profiting at the expense of people in need started out just like these children, with all the potential in the world. Those who once looked out for younger kids like my girls are now making "logical" choices with perverse results. It's hard to figure out when the transition to the "dark side" takes place - when such choices no longer generate any internal dissonance.

One colleague mentioned that he reminds his children that he is raising them for the world in which they will live, not the world he wishes for. I hope that my girls will not only be prepared to live and succeed in this imperfect world, but also to make it a little less imperfect.

The Invisible Wounds of War

2009-12-20T17:00:00.000-08:00

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Last week I had the privilege of reviewing research grants for Congressionally Directed Medical Research Programs (CDMRP) focusing on psychological health and traumatic brain injury. The focus is on innovative research that has immediate applicability to veterans and active duty personnel involved in Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF). The review panels included an impressive array of military and civilian scientists, and consumer/advocate reviewers. We had reviewed the proposals and were convening to discuss our impressions and achieve consensus on our ratings.

My civilian perspective was enriched by military reviewers who described the unique aspects of combat-related PTSD. I had never heard the term "moral injury" before, but it captured the essence of a warrior's ethical dilemma in conducting themselves in modern warfare. Two consumer reviewers were combat veterans with both PTSD and multiple concussions. One, a former Army Ranger sniper, described his residual cognitive deficits, mood swings, and struggle to create a life after a medical discharge that ended the only career he had ever desired. We discussed his reflections on reading the Aeneid, the Odyssey, and Ajax, all of which describe ancient heroes struggling to create a new life after war.

Perhaps the most perverse element of the experience of PTSD and TBI is that, on the outside, these wounded warriors look "normal". This, in addition to the stigma of psychiatric illness (many symptoms of mild TBI appear "psychiatric"), create barriers to recognition and management. Based on the quality and quantity of proposals our panel reviewed (there were many more), it appears that the "signature injury" of the Gulf War is being recognized and addressed.

"Mild" TBI and the "Silent Epidemic"

2009-10-28T17:06:00.000-07:00

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Yesterday I had lunch with a dear friend and former co-worker. She is a dynamic mental health professional who was the creative genius behind a national program to train mental health organizations on implementation of recovery-oriented, consumer-centered programming. We've kept in touch since I left academia and continued to develop our insights on transformational change and improvement of mental health services.

Over lunch she described how, a year and a half ago, she was injured in a car accident. She had mentioned the accident to me a few months ago, saying she had a mild concussion , but at the time didn't mention any complications. Only recently and in retrospect did she understand just how much it had affected her.

She described difficulties with multi-tasking, attention and concentration, and fatigue, listing the post-concussional cognitive impairments that I had treated and studied while in practice. Over the past few months the fatigue has diminished, though she had never eased up on her grueling schedule of training, writing, and consulting.

More importantly, these symptoms undermined her trust in cognitive skills she had previously taken for granted. She remains an articulate, brilliant professional, and I didn't notice anything other than a scheduling mix-up when we were to meet for coffee last month. But she notices the difference, like a world class athlete with an injury that ever so slightly dulls her edge. I wonder how many other "mild" traumatic brain injuries (TBIs) are overlooked or leave individuals with an uneasy sense that something is different. The CDC describes TBI as a "silent epidemic", accounting for over 2 million ER visits a year. It's entirely possibly that my friend's case wasn't even counted.

Virtual companions on life's journey

2009-10-14T16:45:00.000-07:00

Image by R. Cao via Flickr

I've been working my way through a fascinating book, "Becoming a Resonant Leader." It's a workbook, much of which involves taking stock of one's core values and personal vision through a series of written exercises. One, which involved a review of major personal and career transitions, asked me to detect any patterns during these critical points in my life. I would have to say that the most important difference in my most recent transition was my involvement in social media.

I joined LinkedIn about two years ago after my brother invited me to connect. Over time I became more familiar with the functionality of the site and in the process connected with existing and new contacts. This has led to virtual collaborations with several connections I met through groups and discussions. I then began experimenting with Twitter and blogging earlier this year as I felt another transition coming on. While I still consider myself a semi-noob at this, I still find that being part of this online community has remarkably eased this transition.

Previous career moves, even though they were invariably positive, were always accompanied by a sense of isolation and alienation. Leaving behind an existing infrastructure of relationships to take on a new role in a new organization always entails personal and professional risk. However, in this case, I have a network of companions, some of whom I've never even met, who I've connected with out of mutual respect and a sense of common purpose. This common purpose transcends any job description or corporate culture.

Shortly before my move I read "Who's Got Your Back" by Keith Ferrazzi. It describes the value of a go-to team of individuals who serve as a personal board of directors. It's a great idea, though requires an investment in time and effort to go the whole nine yards. In my case, just having people with whom I feel a kinship of purpose and values is good enough. This transition has been unique for me.

Our Brains - the undiscovered country (until now)

2009-09-27T16:22:00.000-07:00

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Two recent articles remind us that the brain is the organ of thought. In the first, researchers at UC Berkeley are using functional magnetic resonance imaging (fMRI) to study how regional blood flow changes after subjects have seen an image. They were able to identify, through the scans, what the subjects had just seen. This is eerily similar to the premise of the Robin Williams movie, "The Final Cut", in which brain implants record every single memory for posterity. In the extreme, we could in fact find that privacy is no longer possible - that every single thought, encounter, and perception is encoded within our brain. George Orwell's "1984" would need to be completely re-written to accommodate this sort of technology.

Another researcher, David Amodio, at NYU, will study neurological mechanisms underlying racial bias. Since bias, like all human cognition, involves complex associations of various memories, perceptions, and affects, it is perfectly reasonable to expect that certain patterns can be identified. The question is, what to do about it? While racial bias is considered a "bad" way of thinking, can this research be applied to identify disloyal subjects in a police state? Still worse, could it be used to monitor the progress of "treatments" to "fix" the thought problem, or guide "targeted therapies" to "fix" the "aberrations"?

Donor organs, stem cell research, and other major medical advances trigger ethical debates regarding the definition and sanctity of life. The time will soon come when we'll need to address deeper issues of privacy and freedom among the living.

Health reform goals we can all embrace

2009-09-19T08:43:00.001-07:00

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Trying to keep up with the rhetoric, hyperbole, and drama associated with the health reform process, I'm struck by how we're losing track of the two fundamental problems:

Health insurance is unavailable to many people
While the actual numbers are subject to dispute, no one believes that everyone who wants coverage has it. A Harvard study found that uninsured working-age Americans have a 40 percent greater risk of death than their commercially insured counterparts. Health insurance, with appropriate incentives for preventive care and effective management of chronic illness, can save lives. Whether it can save money is a different question.

US healthcare is costly, inefficient, and sometimes unsafe
Whether this is due to perverse economic incentives or the evolution of our "system" from an array of legacy pieces, it's clear that waste and error are built into our processes of care. Again, no one argues this point; how to fix it is the challenge, since you can't simply take a hospital "offline" like a server to install a new operating system. Similar concerns have delayed upgrading our antiquated radar-based air traffic control system to a GPS-driven system.

As clearer minds prevail and the political jousting dies down I optimistically believe that we'll achieve forward movement toward these goals. How far we go depends on the discipline of Congress to keep their eyes on the ball - broader health coverage and improved healthcare.

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Crime and Punishment in Pharma

2009-09-07T12:37:00.000-07:00

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Here is a photo of Charles Pfizer, the German chemist who founded what would become the world's largest pharmaceutical company. The Justice Department recently announced a record-breaking $2.3 billion fine against Pfizer (the company, not the man) related to allegations of off-label promotion of products in addition to luxurious consultant meetings at resort locations. Off-label promotion is considered a violation of the federal False Claims Act. The federal government, which pays for a substantial portion of all pharmaceuticals through Medicaid and Medicare Part D, can recover damages if a company makes claims not supported by substantial evidence (i.e. the FDA-approved label). The lavish consultant meetings are considered violations of the Anti-Kickback Statute designed to prevent physicians from being induced to generate services paid for by Medicaid or Medicare. Originally instituted to prohibit hospitals from paying physicians for referrals, this is also applicable to medications, devices, and diagnostic tests.

The Justice Department described the fine as a warning to all manufacturers and branded Pfizer a "repeat offender". Bill Vaughan of the Consumers Union is quoted in most articles as stating that such fines are considered a "cost of doing business". His comment reflects the fact that company shareholders ultimately bear the cost of these settlements - the fines will be applied to 2008 earnings. Thus far only two Pfizer employees have been held personally accountable. They were both sales managers for Bextra, only one of the multiple products for which Pfizer is being fined. Pfizer's internal checks and balances apparently broke down on a large scale, similar to the accounting failures that inspired the Sarbanes-Oxley Act.

I share Mr. Vaughan's view that federal fines will only create expense items in annual statements rather than driving a shift in promotional practices. Business consultants advise making individuals explicitly accountable for their decisions. Charles Pfizer didn't make bad decisions regarding promotional compliance. Neither did the company that bears his name. The individuals who did, either by commission or omission, remain obscure footnotes (or cooperating witnesses) in the case against the corporate giant.

New treatment for schizophrenia and bipolar disorder

2009-08-17T16:52:00.000-07:00

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The FDA recently approved Saphris (asenapine) for the treatment of schizophrenia and manic or mixed episodes in bipolar disorder. I'm happy. Not just because a good friend recently took a position with Schering-Plough, the manufacturer (soon to be acquired by Merck). And not out of some perverse spite towards my previous employer, a direct competitor in the lucrative antipsychotic market.

I'm happy because, for someone out there suffering from unremitting symptoms or intolerable side effects, this will represent a major breakthrough in their recovery. It might save their job, their marriage, even their life. As a psychiatrist I've learned about the specific receptor interactions that supposedly mediate and moderate efficacy and tolerability of psychotropic medications. I've also met more than my share of patients who experienced benefits or side effects that didn't fit my orderly pharmacological models. Clearly they didn't get around to reading chapter 46. Or was it 47?

In accepting my patients' experience as valid (only took about 10 years), I've realized that bell curves have long tails, and in those tails reside many decent people who are labeled "difficult". Their receptors are perhaps more or less sensitive, have different affinities, and may be associated with different neurodevelopmental anomalies. In short, they are one in a million. Maybe one in a thousand. The asenapine schizophrenia and bipolar disorder clinical trial programs enrolled about 2300 patients combined, about half of whom actually received the medication. On average, patients receiving the medication improved more than those receiving placebo.

Will they do better compared to other available medications? This is the classic argument against "me too" drugs - they're all the same except the color scheme on the ads. Psychiatric conditions are so heterogeneous that it's hard to match the right patient to the right medication - sometimes a combination of medications. Sometimes a patient can't tolerate a high enough dose to receive the benefits. Sometimes it just doesn't work no matter how high the dose. But clinical trials show the same average effect across all drugs within the class. These patients should know better.

Every new medication gives hope to individuals, not averages. Maybe this one will give at least one person the relief they've heard others patients talking about. I'm happy for my friend at Schering. But I'm even happier for patients who might find that asenapine provides a benefit that they've been promised with the other half dozen new medications over the past 20 years. With a new option there's one more bite at the apple.

No summer vacation for Congress

2009-08-16T14:53:00.000-07:00

lengua einstein" style="border: medium none ; display: block;" height="240" width="179">Image by Cromo via Flickr

"We can't solve problems by using the same kind of thinking we used when we created them."

- Albert Einstein

On a local news channel I watched a normally media-savvy House representative become testy with a television crew before a healthcare reform town hall. He acted as though the media were trying to set him up. Later, during the meeting, he endured angry accusations and diatribes from his constituents. Rather than communicating his understanding of the issues, he spent the meeting calming an angry mob. The question is, what were they angry about?

I'm not suggesting that people have nothing to object to. I just can't figure out who's angry about what. Sarah Palin's "death panels?" Taxing employee health benefits? Socialized medicine? Of the three, only the second strikes me as having been seriously discussed as an option. What I hear is the voice of a public reeling from a major blow to their financial health engineered by powerful, underregulated robber-barons, who are worried that a second calamity will impact their physical health.

In this post-Cold War era we don't have an evil empire to fear. Faceless corporations, with the collusion of government elements, prey on the unknowing masses. Like the human batteries of the Matrix, we are the food on which the dominant species feeds, anesthetized by the illusion of security. Or so the story goes in the headlines and more than a few films over the past few years.

Since no one has "the answer", every solution is a threat until proven otherwise. At least we have some agreement on the problem. Healthcare spending continues to eat up a growing portion of our GDP with little to show for it. The causes are a source of debate. We blame the pharmaceutical industry, which spends roughly $1 billion to develop a single drug from test tube to pharmacy, yet medicines account for only 11% of total health expenditures. We blame insurance companies for profiteering, yet the industry has margins of only about 3%. Arrogant doctors ignore evidence-based practice guidelines and prescribe unnecessary treatments to line their pockets or avoid litigation. Malpractice lawyers? Get your pitchforks and torches.

We're in the midst of an historical debate of epic proportions. Whatever comes of this, the status quo is clearly not an option if America is to remain an economic, scientific, and ideological leader in this century. The debate, at times uncivil and irrational, is forcing us to confront a host of ugly facts that we've ignored for too long. I don't believe we'll end up with a carbon copy of the European healthcare model. Americans value choice and inclusiveness too much and historically have demonstrated a resilience and ingenuity in the face of steep challenges. Somehow we 'll find our way forward. We're too stubborn not to.

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Of Golden Geese and Dinosaurs

2009-08-09T17:04:00.000-07:00

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IMS Health estimates that by 2013, pharmaceutical products with annual sales of about $135 billion will lose patent exclusivity; about $90 billion of those branded sales will be in the United States. Now the NY Times reports that PhRMA, the pharmaceutical industry's trade group, plans on spending up to $150 million in advertising to support Obama's healthcare reform plan. Some believe that this is a means of ensuring that the administration will not ask the industry for more than the $80 billion over 10 years it has committed to help Medicare beneficiaries afford branded medications. So what's wrong with that?

Critics of Pharma's "excessive" profits can rightly point to the multi-billion dollar "me too" drugs launched in the 90's to cash in on an unconstrained market. With 20-20 hindsight we could claim that excessive dividends and executive compensation should have been diverted to paradigm-changing R&D in order to justify pricing the next generation of pharmaceuticals as profitably as the current litter.

Pharma has been a victim of its own success, delivered both clinical and economic returns in the 90's. The world is demanding a repeat performance - screening 10,000 compounds for every one approved by the FDA, only now with better efficacy, safety, or tolerability. In a twisted version of "Survivor", companies are merging, acquiring, in-licensing and out-licensing in order to survive until the pipeline delivers.

Generic proponents claim that with costs of only pennies per pill, Pharma is gouging the public. That first pill cost the developer about $1 billion to bring from test tube to pharmacy. The developer also covers the costs of the 9,999 candidates who failed in the development process.

The $135 billion a year annual sales to be lost within 4 years will be gone forever, and no one believes the "good old days" of easy blockbusters will ever return. If our medicines are good enough right now, we don't need more innovation and the associated R&D budgets funded through premium-priced branded pharmaceuticals. In that case, we should allow the research-based pharma companies to wither and die, making room for generic manufacturers with offshore plants and cheap labor. Of course, since a large portion of their profits occur just after patent loss during which they charge as much as 80% of the brand price, some of them will die too.

The $80 billion in cost savings offered up by the industry is a small fraction of all pharmaceutical spending projected over the next 10 years. However, with patent cliffs approaching, more and more pharmaceutical revenue will go to generic manufacturers, who have committed... how much?

85 days to go

2009-07-25T18:32:00.000-07:00

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So I just finished my first week in a new job. I can find the bathrooms, cafeteria, and coffee rooms. Physical needs met. Migrating up Maslow's hierarchy of needs, I'm still figuring out Lotus Notes, having called the help desk enough that my fingers can dial the extension themselves. My browser bookmarks are just about set up and I've gotten my new contact info out to most of my external network. Michael Watkins describes the first 90 days as a critical period of personal and organizational transition. This "honeymoon period" is less about infatuation than grace period for capacity-building that will sustain future productivity.

Boris Groysberg and colleagues describe how, when successful candidates are brought into a new organization, they and their new employer may suffer reduced performance because personal success is often a function of relationships that have been left behind. If new sustaining relationships are not developed, this can cripple the new hire.

One solution is to hire intact teams (Groysberg's "Lift Out" concept), with existing interdependencies that can improve the odds of success. This can get expensive and create legal problems. A more pragmatic solution is to hire people with an external network and the capacity to build new internal relationships quickly.

I'm meeting smart, dedicated, energetic people every day yet distinctly aware that I'm helpless to contribute my full potential until those introductory meetings evolve into partnerships. During my interviews I described how my prior successes came from great relationships with terrific people. Now my task is to meld my external network with a growing internal network. Introducing great people to other great people is always a pleasure.

Comparative effectiveness or comparative cost-effectiveness?

2009-07-22T10:32:00.001-07:00

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A recent article in NPR describes the debate erupting over comparative effectiveness research (CER). This has been proposed as the main engine behind healthcare reform. The rationale is based on the assumption that pharmaceutical and device manufacturers reap billions of dollars in profit due to the overuse of unnecessary and overpriced products that offer no advantages in safety or efficacy compared with cheaper, generic options, including watchful waiting.

Carolyn Clancy, head of AHRQ, states that, left to their own designs, manufacturers would avoid such studies. Whether or not this is the case (I'm aware of a number of "head to head" clinical trials sponsored by manufacturers), it's important to understand that CER is designed to compare effectiveness. Somewhere along the way everyone has started to assume that costs are built into the analysis. Given the state of the economy, it's not surprising that everyone naturally assumes cost containment is the endgame.

Sean Tunis, former Chief Medical Officer of CMS, emphasized that cost containment is simply rationing of health resources. While CER might enable us to determine which costs are worth containing - ostensibly the "ineffective" costs can be contained - both Clancy and Tunis point out that the goal is not to deny care, but to use existing resources to the best effect. This could mean medication instead of surgery or vice versa depending on which works best. It could mean generic drugs instead of branded drugs or vice versa depending on which works best. However, if both treatments are equally effective, is the more costly choice denied? This is an entirely different question.

CER will provide important insights into what different treatments can and cannot accomplish. However, it's important to have an idea of what we intend to do with the results.

Eve of a new job

2009-07-19T17:41:00.001-07:00

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Tomorrow I start my new job. Health outcomes in a mid-sized biopharma company focusing on oncology. I had been enjoying the work at my previous job, was delivering results and receiving praise, but felt restless. The people were great, the work interesting, decent pay. What's not to love, especially in this economy?

Against my common sense I followed my instincts - a sort of Malcolm Gladwell "Blink" moment when everything came together. After I committed to leaving my current job, my world changed inside and out. My interest and engagement as a non-profit board member increased. I started reading more - not just about health economics, econometrics, and leadership skills. Frans Johansson's "The Medici Effect" sucked me into a nexus of connections that don't make sense until they make perfect sense. I started rereading "The Peloponnesian War", digging out the faded paperback copy I read nearly 30 years ago as a college freshman.

Externally I met up with some terrific people on LinkedIn more reflective of my eclectic range of interests rather than colleagues and headhunters. I was invited by a friend to teach a course in healthcare manangement at a local college. I've reconnected with my pre-pharma academic colleagues to collaborate on health services research.

Could I have accomplished all of this without a job change? Of course. Would I have? Probably not. My wife and oldest daughter ask if I'm nervous about starting my new job. I can't relate - it seems as natural as breathing.

Healthcare reform or "sick care" reform?

2009-07-14T17:03:00.001-07:00

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We understand many illnesses are causally related to behavioral risk factors - cardiovascular disease and diabetes are associated with obesity and inactivity, lung cancer is related to smoking. Much of the discussion around healthcare reform is how to sustainably finance treatments that relieve disease and prolong human life. However, since healthcare is predominantly devoted to treating disease, is it really "healthcare", i.e. caring for health?

Primary prevention is the term used when describing how we avoid the onset of disease. Maintaining a healthy body weight can drastically reduce the risk of cardiovascular disease, diabetes, certain malignancies, and even arthritis. Who owns preventive care? We usually assume that this is the role of the primary care provider (PCP), but is that realistic?

I see my PCP once a year for my annual checkup unless something goes wrong. What are his chances of reducing my likelihood of developing a costly disease through his education and counsel? By the time you see your doctor frequently enough for him or her to do so, the horse has already left the barn because you're already sick. Early diagnosis and treatment brings us to the realm of secondary prevention, i.e. preventing complications of the disease. Tertiary prevention reduces existing impairment or restores function due to established disease. This is where most "healthcare" resides - treating illness.

If we're fortunate enough to be healthy, the "healthcare" system has nothing to offer us because we have few if any contacts with it. When we finally get sick the system responds with all of the diagnostics, medication, and procedures that cost so much money.

Maybe a great long-term investment in "health information technology" (HIT) will be social networking models that help populations prevent the onset of costly diseases. That sounds like real "health" care to me. In the meantime, we still need to find more efficient ways of using the resources we have to treat the diseases we have. So we do need to reform "sick care".

Alzheimer's Disease Drug Treats Traumatic Brain Injury

2009-07-12T14:45:00.001-07:00

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"Alzheimer's Disease Drug Treats Traumatic Brain Injury". Great news in the search for treatments for TBI. My first post on this blog expressed hope that someone would connect these adjacent dots. Investigators at Georgetown University Medical Center found that a gamma secretase inhibitor reduced the amount of beta-amyloid accumulation in the brains of mice subjected to experimental TBIs.

The critical point here is that this class of drugs represents a means of preventing damage to due TBI. It's widely recognized that "repairing" brain damage is much more challenging that prevention of this damage. The availability of a preventive treatment would have implications for military and athletic uses. Blast injuries and sports concussions are increasingly recognized as sources of impairment and disability. These developments could usher in a new era of brain treatments that are proactive rather than reactive.

Hospital readmissions drive continued debate

2009-07-10T18:06:00.001-07:00

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The New York Times cites data indicating that hospitals in the state have among the highest readmission rates in the country. The simple, "market-driven" explanation is that the hospital reimbursement - payment for each admission via diagnosis related groups (DRGs) rewards this inefficiency. The hospital gets paid twice for the same patient, only the second admission is much shorter - really an extension of the first. Payment is the same. Cha-ching!

This interpretation has drawn considerable criticism. First, the suggestion that hospitals and healthcare professionals would actually try to discharge unstable patients in order to readmit them for financial gain is disturbing, to say the least. Moreover, hospitals in some communities treat sicker patients. There's considerable evidence of disparities in access to and quality of healthcare delivered in low income communities. With less preventive care and a tendency to delay treatment until more serious illness, patients hospitalized in New York City may have less access to critical post-discharge care.

Case mix adjustment and follow-up care quality are critical to assessing hospital outcomes. The transition from inpatient to ambulatory care involves transfers of accountability, especially when the hospital doesn't "own" the aftercare services through visiting nurse programs or outpatient clinics.

There is universal agreement that the process of care is highly variable and leads to unnecessary cost and suffering (hospitals are NOT fun places). The debate is not about the "what" but the "why". Quality advocates and researchers have known this for years - now we may have a collective willingness to act on a larger scale. Let's hope it doesn't degenerate into finger pointing and draconian regulations that help no one.

A heretic in the cult of medicine

2009-07-03T12:39:00.000-07:00

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One of my favorite lectures to first year medical students was on clinical interviewing. I would warn them that the next four years of their lives would indoctrinate them in the "cult of medicine". Knowing that I now had their attention, I proceeded to describe the various ways our profession transformed them from lay people to members of an exclusive sect:

Language: we learn the Greek-derived terms for bodily changes associated with health and disease - "febrile" instead of "feverish"; "micurition" instead of "peeing". True acolytes are able to run through a case presentation in the ancient shorthand language unintelligible to outsiders. When this occurs in the presence of the patient, I'm reminded of how my parents spoke Korean in front of me when they had something "private" to discuss.
Vestements: nearly every medical school has the "white coat ceremony", that first-year ritual during which students receive their ill-fitting short white coats. Short white coat = medical student. The Washington Manual of Medical Therapeutics must go in one of the oversized pockets. The stethoscope, draped across the neck, completes the uniform. Long white coat plus stethoscope across neck = house staff. Long white coat plus stethoscope in pocket (no more Washington Manual) = attending physician. Scrubs are the ceremonial vestements used to signify that the wearer is in the OR or on-call, the overnight vigil in the temple of healing.
Scripture: Medical students are trained to document their assessments in the structured format developed by Sir William Osler over a century ago. All physicians know the code and can quickly translate many arcane abbreviations. However, due to some straying from the canon, the Joint Commission has mandated the elimination of certain abbreviations that may cause medical errors and harm.
Vows: the Hippocratic oath ties us to a shamanistic tradition stretching back millenia, obligating us to protect and advocate for the interests of our patients.

Medicine is not a bad cult. In fact, the cult-ure is responsible for the strong sense of purpose that permeates the field. None of my "rich" friends are doctors. The downside is that our training makes it hard to remember what it was like when an emergency room was confusing, foreign and scary. This makes it hard to communicate effectively with patients and families.

So I told my students to remember what it's like now, struggling to remember all the weird terminology and bodily processes. Hold on to that confusion, embrace it as a vital part of our humanity. Without it we have no common ground with our patients and lose much of our legitimacy as agents of change and healing.

Master sages in the cult of medicine can complete a diagnostic interview through what appears to be a warm, personable conversation. They are masters of two worlds - medical science, and being a regular human being. Like the Jedi master who no longer requires a light saber to dispatch evildoers, the true medical master realizes that they (not their white coats, stethoscopes, or advanced technology) are the ultimate tool of healing.

Yes, medicine is based on scientific evidence. But our power is not in our superior knowledge. Any PDA can serve that function. It rests solely on the strength of our humility and humanity.

Why I re-activated my medical license

2009-06-30T18:07:00.000-07:00

Three and a half years ago I said farewell to my patients and joined a pharmaceutical company. Over the prior four years I was increasingly involved in hospital administration and had limited my practice to a half day clinic each week and inpatient rounds every sixth weekend. As an administrator I hoped to improve population health by influencing the health system where I worked.

As a psychiatrist I was privileged to have my patients share their hopes, fears, tragedies and victories with me. It was in witnessing their courage to confront their demons, acknowledge their flaws, and trust another human being (all too often in spite of multiple betrayals and abuses) that I was challenged to accept my own frailty.

Two years ago, I decided that I wasn't going to practice medicine in the foreseeable future and placed my license on inactive status rather than spend four hundred plus dollars every two years to renew it. A part of me mourned the loss, but I had other things to focus on. It took a former resident of mine who came to pharma and went back to private practice to convince me that I still needed to continue to help one patient at a time.

So I pulled together my continuing education certificates, sent in the money order (who uses money orders??), went to the fingerprinting facility, and today received the familiar paycheck-like blue envelope in the mail.

I am once again a licensed physician, ready to practice my craft. Now I need to find a practice setting that will cover liability insurance and accommodate my very limited availability to serve on a pro bono basis. I have a few academic and public sector options that I'll pursue.

My day job is health services research - population health, policy, health economics. But the individual, private battles with disease and despair fought every day by patients and their healthcare teams are what make it meaningful. I need to get back on the front lines.

Does healthcare pay for itself?

2009-06-26T16:40:00.000-07:00

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Healthcare reform that emphasizes comparative effectiveness research may lead some to believe that we'll be able to create a system that pays for itself. In reality, almost nothing in healthcare pays for itself. Even so-called cost effective treatments don't actually save money. You simply get a year of perfect health (a "quality-adjusted life year" or QALY) for less than $50,000.

"Cost effectiveness" simply means that we pay an "acceptable" amount for the benefit received. Just as you can't get a yacht and a rowboat for the same price, improved health comes at a cost. QALYs are a simple denominator, but we Americans are very diverse and pretty darn complicated and take issue when someone else tells us what our quality of life is worth.

Don't blame patients for health care costs

2009-06-21T16:41:00.000-07:00

The Obama administration is concerned about the unexplained geographical variability in health care costs. One possible explanation is that doctors and hospitals are responding to patient demands for increased services. Researchers at Dartmouth surveyed Medicare beneficiaries and found that, at the individual level, a patient's preference for specialist treatment and diagnostic tests predicted how much they cost.

However, this doesn't explain why some regions are more costly, because those regions don't have more "high utilizers" than low cost regions. Rather, the local systems are more costly in their processes of diagnosis and treatment, for high and lower utilizers - basically anyone who enters the system.

More research to explain the variations at the systemic level is needed to guide rational spending that delivers results.

Fatherhood is good for guys

2009-06-21T07:40:00.000-07:00

According to a study by the American Psychiatric Association, over six million men in the US suffer from depression. Over 90% said that their role as a father would have an impact on their decision to seek help for this. This is important, because recent research indicates that psychiatric problems in fathers may be as important as problems in mothers.

Implications of these studies are that, fatherhood motivates men to seek counseling and treatment for their own psychological burdens, which in turn benefits the kids immensely.

Fatherhood is complex. We're supposed to be strong, resilient, yet nurturing. As a father of three brilliant, beautiful daughters who still think I'm pretty cool, I can't imagine a better source of inspiration to be a better man.

Controlling health care costs vs. controlling disease

2009-06-18T17:38:00.000-07:00

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One in four patients with multiple sclerosis are not filling their prescriptions due to high out of pocket costs according to a study by Prime Therapeutics, a pharmacy benefit management company. Cost sharing is designed to accomplish at least 2 things:

Create financial incentives for patients to request "preferred" drugs, i.e. those that are cheaper
Provide the health plan with a "refund" from the patient to offset the costs of the medications. Health plans also receive "rebates" from pharmaceutical companies in exchange for formulary placement

Unfortunately, patients will sometimes simply not take the medication, or take it sparingly to stretch out the supply. No one wins in that situation.

Diagnosing Alzheimer's Disease

2009-06-18T05:55:00.000-07:00

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Near-infrared (NIR) biospectroscopy of blood plasma has demonstrated promise in discriminating between those with Alzheimer's disease and healthy elderly individuals. Currently the gold standard is post-mortem brain biopsies, which is not helpful in planning treatment.

Other diagnostic approaches include measurement of spinal fluid proteins, which requires a spinal tap, or using nuclear brain imaging an expensive procedure. A blood test may revolutionize the treatment of Alzheimer's disease, paving the way for earlier use of disease modifying treatments that may slow or arrest the progression of disease.

Comparative effectiveness - another approach

2009-06-16T17:16:00.000-07:00

Efficacy is determined in experimental trials, and answers the question "can it work?" under ideal conditions. Effectiveness answers the question "does it work?" in real world conditions.

"Observational studies" are an analysis of what people are doing outside of experimental settings. As a physician I never "randomized" my patients. Rather, I used my experience, knowledge of the literature, and assessment of the situation to decide what options to recommend (the patients decide what recommendations to follow).

The main criticism of such studies is that they're not randomized. But the true test of "effectiveness" is not whether the drug works in an experimental protocol that controls every aspect of treatment. Rather, a drug is effective if I can use it to good effect in my patients.

A scalpel may be really sharp, but if I can't operate with it, how effective is it?

Comparative effectiveness and other fine myths

2009-06-13T18:40:00.001-07:00

What is comparative effectiveness research (CER)? Most think it's simply head to head clinical trials to prove which drugs are better. Another approach is "health technology assessment" (HTA), in which multiple clinical trials are analyzed for indirect comparisons.

What's wrong with this approach?

Many patients enrolled in trials are "ideal", rather than "normal", i.e. they often lack the many concomitant illnesses that travel with the disease of interest in the trial.
Higher adherence in trials is the norm; non-adherent subjects are removed. In medical practice, incomplete adherence is the norm.
Dosing and treatment with other medications in clinical practice often doesn't resemble what is studied in the trials.
Optimal access to monitoring, follow-up, and the absence of insurance hassles make trials more like Club Med than Outward Bound.

With this is mind, the current perceptions of CER resemble fantasy football more than real-world effectiveness. There are other approaches if we're really interested in knowing the answers.

Starting HIV Therapy Earlier Yields Better Clinical Outcomes

2009-06-10T11:45:00.000-07:00

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A randomized controlled clinical trial in Haiti funded by NIH was halted early after it became clear that starting patients with HIV on antiretroviral medications when they have higher CD4 T-cell counts (250-300) led to improved survival compared with starting at <200.

Healthcare Spending Varies Widely by Region

2009-06-09T05:44:00.000-07:00

The NY Times reports concerns from the administration and Congress regarding the wide disparities in healthcare spending by region. With a national average of $8,304 per Medicare beneficiary in 2006, spending ranged from $9,564 in New York York to $5,311 in Hawaii according to the Dartmouth Atlas of Health Care.

Proposals to address this include capping payments in regions with higher spending rates, or exempting regions with lower spending from across the board Medicare cuts. Moreover, a recent study in Health Affairs found no correlation between quality of care and hospital spending.

Patients aren't 100% honest with doctors

2009-06-08T10:32:00.000-07:00

The LA Times reported that up to 45% of patients don't accurately inform their physicians - either stretching the truth or outright lying. The potential consequences of this can be costly and catastrophic - misdiagnosis, harmful drug-drug interactions, inappropriate diagnostic tests and procedures. The death of Libby Zion is attributed to a drug-drug interaction resulting from the on-call physician not being informed that she was taking a drug with a potentially lethal reaction with the Demerol he administered.

Communication is critical to safe, effective, and efficient healthcare. While medical schools are developing curricula to improve clinical communication, cost containment prevents them from using these skills, opening up opportunities for error, waste, and harm. All of these are costly, even without the price of lost patient dignity.

Depression in the Recession

2009-06-07T17:07:00.000-07:00

The Integrated Benefits Institute (IBI)just released their report on the costs of depression on the work force. Surprisingly, 80% of the lost productivity due to depression is in employees who are not on short term disability - instead they take sick leave and are less productive.

Stigma is a major barrier to effective diagnosis and management of depression, which is not an all or nothing condition. At the most severe end of the spectrum it can suck will and spirit, leaving a dead shadow, sometimes wracked by guilty, self-hating delusions and hallucinations. In milder forms it can resemble the existential crises we all periodically experience - are we good enough, is life/work/family worth the effort? At either extreme, no one wins. Employers suffer lost productivity, employees and those around them just suffer.

As employers shift more of the costs of all health care to employees, it's hard to fathom why. Healthcare as an operating cost is a drag on profitability. Healthcare as a capital investment is a strategic advantage. Translation of employee health to earnings per share might help clarify just where this line item belongs.

Comparative effectiveness - not just about pharmaceutical reimbursement

2009-05-28T18:05:00.000-07:00

With $1.1 billion in the American Recovery and Reinvestment Act (ARRA) allocated for comparative effectiveness research, HHS claims:

"Comparative effectiveness research provides information on the relative strengths and weakness of various medical interventions. Such research will give clinicians and patients valid information to make decisions that will improve the performance of the U.S. health care system"

Improving the performance of the health care system will require improvements in the system itself. In 1999 the Institute of Medicine (IOM) described these costly deficiencies in "To Err is Human". Comparative effectiveness research could help identify processes and procedures associated with maximal benefit, minimal risk, and reasonable cost, reducing waste and harm.

Unfortunately, many stakeholders are limiting CER to specific pharmaceutical products, which represent only a fraction of the total healthcare spend.

CER can embrace many factors that affect the safety, effectiveness, and efficiency of the healthcare system, such as quality improvement and adoption of health information technology (HIT). The HIT component in the ARRA could be considered one force to drive true CER, not a "nice to have" add-on.

If we can change our perception of healthcare from an operating expense to a capital investment in the economic and social future of nations and corporations, CER could drive the sort of change demanded over a decade ago by the IOM.

Health Outcomes: What Now? What Next?

2009-05-25T16:50:00.001-07:00

The age of blockbusters is supposedly fading. Comparative effectiveness, value-based reimbursement are upon us, supposedly to ensure that pharma no longer develops "me too" (or "me too late") drugs.

Economists, epidemiologists, and health services researchers, are self-selected quantitative types. Historically our medical and commercial colleagues expect us to crunch numbers in our cubicles to "make this product cost effective". Since they clearly don't understand and appreciate the implications of their expectations, HEOR staff will need to develop strategic, matrix and political skills in order to guide internal stakeholders. Technical tasks can always be outsourced, but asking the right questions can never be delegated.

The "right" questions are medically informed questions, not hypothetical head to head economic analyses that assume 100% diagnosis and treatment of all cases and complications, and perfect adherence to all regimens. The answers to relevant questions would reflect silliness of using unit price of individual products to assess value in a healthcare system is designed to achieve inconsistent and often mediocre results.

Alzheimer's and traumatic brain injury

2009-05-24T17:49:00.000-07:00

Traumatic brain injury (TBI) accounts for up to 1 million emergency room visits annually in the United States and has been called the "signature injury of the Gulf War". The relationship between TBI and dementia is somewhat contradictory, though a systematic review and meta-analysis of 15 case-control studies identified a 58% greater prevalence of prior TBI in patients with AD (Fleminger et al. 2003). In a human postmortem study of 90 patients who died of TBI, 52 percent of patients with beta-amyloid deposition had the apoE є4 allele compared with only 16% of those no deposits (Nicoll et al. 1995). Beta amyloid and apoE are also associated with Alzheimer's disease (AD) - the amyloid plaques are one of the signature signs of AD in the brain. This is highly suggestive of a common pathophysiological pathway for the development of AD and TBI-associated brain damage.

There are numerous molecular candidates being developed among large and small pharma companies for AD. The new agents are designed to be "disease-modifying", i.e. to change the course of the illness rather than simply replacing lost acetylcholine. Reducing the production and accumulation of beta-amyloid in the brain is one goal of these treatments. Given the potential for benefit in TBI, it's puzzling why we're not seeing more research in this area.

Let's put it in perspective. Most TBIs are mild, i.e. "concussions" that lead to brief unconsciousness or mild confusion for a bit - say 15 minutes or so. Most of these don't even lead to an ER visit, so you can multiply the 1million annual visits by several fold to estimate the incidence of mild TBI in the US. Think sports concussion. Remember Andre Waters? His brain atrophied from all of those impacts during the course of a distinguished NFL career.

A medication that could reduce or negate the effects of chronic, repetitive low to moderate level head trauma would provide a remarkable benefit to contact athletes everywhere, not to mention stuntmen, soldiers, and others in high risk occupations.

With a potential target market of millions, it's simply baffling why this hasn't taken off. A huge unmet need adjacent to an area of intense investment and investigation. It seems TBI is hiding in plain sight - perhaps because pharma scientists don't think of Ronald Reagan and Andre Waters at the same time. The one who does will do the world a big favor.