Curing Depression with Light: Let the Sun Shine in

In an elegant Canadian study, light outdid Prozac in a head-to-head comparison as treatment for nonseasonal major depression.

The study design is fascinating. Patients were randomly assigned to one of four groups: (1) light and a placebo pill; (2) Prozac and placebo light (an ion emitter modified to hum softly but emit no ions); (3) light and Prozac; and, (4) placebo light and a placebo pill.

The informed consent process involved deception. Subjects were told that the researchers were comparing light to ion treatment, and that half of the devices would be inactive. They were not told that all of the supposed ion emitters were inactive and all of the light units were active. The ethical rationale for allowing deception was that (a) the study goals could not otherwise be pursued, (b) the study had significant scientific and clinical merit, and (c) the deception posed no significant risks to the subjects.

The most effective monotherapy was light. Prozac alone was barely better than placebo. Light combined with Prozac was the most effective arm of the study, but not by much.

Light has been recognized as an effective treatment for seasonal affective disorder (SAD), but has not been rigorously evaluated for non-seasonal depression. If I were still in practice and saw a non-suicidal depressed patient who preferred not to use medication, I would recommend light treatment as part of our initial approach, combined with whatever form of psychotherapy fit the patient best.

We're a pill-happy society, and psychiatry, alas, has tilted away from non-pharmacological approaches to care. If Cazorp (Prozac spelled backwards) were a new pill that beat Prozac as decisively as light did in the Canadian study, the Cazorp company's stock would go through the roof. If further research confirms the Canadian findings, light should become a standard part of the initial response to depression. But although there's some financial opportunity for device manufacturers, inexpensive do-it-yourself light boxes are relatively easy to construct, so we're not likely to see a light boom analogous to the dominant pill boom.

Money talks, so pills thrive. Light cures, but produces little financial (as opposed to clinical) profit. Ergo, pill-popping wins hands down.

Dr. Andrew Wakefield's Fraudulent Claims about Autism

This month the British Medical Journal (BMJ) published a three part series by Brian Deer, detailing the fraud by which Dr. Andrew Wakefield led parents to see the MMR (measles, mumps and rubella) vaccine as a potential cause of autism.

In 1998, Wakefield and 12 colleagues published a paper in Lancet - "Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children." The article presented 12 cases from the Royal Free Hospital in London, alleging that a severe form of autism and gastrointestinal disorders closely followed administration of the MMR vaccine.

Wakefield's "findings" catalysed a massive anti-vaccine movement in the U.K., U.S. and elsewhere, and suits against the vaccine manufacturers for injury. Unfortunately, as Deer's seven years of research documented, Wakefield's conclusions were not simply wrong, they were based on fraud and driven by rampant financial conflict of interest.

Prior to the "study" reported in Lancet, Wakefield had gone onto the payroll of a lawyer who was preparing to sue vaccine manufacturers for causing autism. Families of developmentally disabled children who believed their children had been injured by MMR were solicited to bring the children to the Royal Free Hospital. Intrusive tests that were not clinically indicated were performed on the children. And, as a massive investigation by the General Medical Council (GMC), conducted nine years after publication of the original article demonstrated, the case reports were distorted and outright falsified to support the "conclusion."

Deer details the business ventures that Wakefield and the Royal Free Hospital concocted, to profit from diagnostic tests Wakefield had patented that purported to allow diagnosis of MMR-induced injury. He also describes, in painful detail, presenting his findings in 2004 to Lancet, only to be met with what appears to have been a coverup.

Deer describes being fought against, blocked from gaining access to sources, and sued, during his long journalistic crusade. The GMC investigation ultimately confirmed all of his conclusions. Wakefield and one of his co-authors were stripped of their medical licenses.

Wakefield's fraud has caused multiple injuries, including: (1) distressed parents of children with autism have been duped into believing the cause of their childrens' disorder is known; (2) uptake of MMR has declined, with episodic outbreaks of all three conditions as a result; and (3) public skepticism in research integrity has been intensified.

Sadly, as the U.S. is seeing with regard to the lies about a government plan to create "death panels," it's vastly more difficult to impugn false claims than to make them in the first place. Initial comments on Deer's BMJ articles include many defenses of Wakefield as the victim of a campaign to hide the truth about vaccines, not as the disgraced perpetrator of fraud that he is.

(For Brian Deer's remarkable articles see here, here and here. And for an accompanying BMJ editorial see here.)

How Much is Life Worth? - An Oncologist's Call to Arms.

Between 1997 and 2004, Medicare spending on cancer drugs rose by 267% compared to an overall rise in Medicare spending of 47%. With an aging population, the cost of cancer drugs will become a progressively greater problem for the U.S. health "system."

A recent issue of the Journal of the National Cancer Institute has a very important article by Tito Fojo, an oncologist at the NCI Center for Cancer Research, and Christine Grady, an ethicist with the NIH Department of Bioethics. "How Much is Life Worth: Cetuximab, Non-Small Cell Lung Cancer, and the $440 Billion Question" calls for a fundamental change in research, the drug approval process, drug pricing, and clinical practice. The analysis and argument will be familiar to ethicists and policy wonks. What's especially important about the article is that Dr. Fojo speaks as a distinguished cancer researcher and addresses his recommendations to fellow oncologists.

Drs. Fojo and Grady don't flinch from using the "c" word - cost:

In some sense, every life is of infinite value, and we naturally avoid confronting the tension between not wanting to put a value on a life and having limited resources. But the spiraling cost of cancer care in particular makes this dilemma inescapable. We, the oncology community, cannot continue to ignore it.

The main example in the article is Cetuximab (Erbitux). Erbitux adds 36 days of life for patients with non-small cell lung cancer, but also adds a number of significant side effects. Conveniently, the study that demonstrated the 36 day extension of survival did not include quality of life measures. At its present cost, adding an average of 36 days of life is the equivalent of $800,000 per non-quality adjusted year of life. Fojo and Grady argue that this is far too much cost for far too little benefit.

The authors urge oncologists to act as true professionals who consider wider societal concerns like the uninsured or the U.S. economy going down the tubes. They don't use the word "narcissistic," but their analysis suggests that a profession that considers only its own perspective is just that. They make six specific recommendations for practice and policy:

1. "Research studies that are powered to detect a survival advantage of 2 months or less should only test interventions that can be marketed at a cost of less that $20,000 for a course of treatment." Here they are using the standard of one quality adjusted year of life for patients treated with dialysis ($129,090) as their standard.

2. Drugs should be priced accordingly.

3. "Drugs shown to be active in one subset of patients should be advocated, approved, and prescribed for that subset only. The marginal benefit, if any, which may be achieved in other patients should not be an excuse to administer a therapy even if it is decided that there is nothing further to be done."

4. FDA approved indications should be strictly adhered to.

5. "The all too common practice of administering a new, marginally beneficial drug to a patient with advanced cancer should be strongly discouraged. In cases where there are no further treatment options, emphasis should be first on quality of life and then cost."

6. "For therapies with marginal benefits, toxic effects should receive greater scrutiny."

Having exposed the chemotherapeutic emperor's new clothes for what they are, Drs. Fojo and Grady conclude:

We must deal with the escalating price of cancer therapy now. If we allow a survival advantage of 1.2 months to be worth $80 000, and by extrapolation survival of 1 year to be valued at $800 000, we would need $440 billion annually — an amount nearly 100 times the budget of the National Cancer Institute — to extend by 1 year the life of the 550 000 Americans who die of cancer annually. And no one would be cured.

The current situation cannot continue. We cannot ignore the cumulative costs of the tests and treatments we recommend and prescribe. As the agents of change, professional societies, including their academic and practicing oncologist members, must lead the way. The time to start is now.

Drs. Fojo and Grady have issued a courageous and compassionate challenge to their fellow medical professionals. It deserves wide attention!

(The article is not yet available without charge, but a summary and paid access to the full text are available here. For Dr. Fojo's web page see here.)

ALS, the Rule of Rescue, and the FDA

The opening paragraph in "Fighting for a Last Chance at Life" in today's New York Times led me to expect what the Brits call "hanging crepe" - using imminent death to blast insurers as uncaring, profit-seekers and the FDA as a callous bueaucracy:

As Lou Gehrig’s disease sapped Joshua Thompson of his ability to move and speak last fall, he consistently summoned one question from within the prison of his own body. “Iplex,” he asked, in a whisper that pierced his mother’s heart. “When?”

Joshua, a vigorous, athletic, married 34 year old father was diagnosed with Amyotrophic Lateral Sclerosis in 2007. Kathy Thompson, Joshua's mother went onto the web, and learned about Iplex, a drug containing an insulin-like growth factor that in 2006 had been reported to stimulate growth of the nerve cells involved in ALS (in tissue culture). The growth factor had been tested on ALS patients and was found to be ineffective, but Iplex combined the growth factor with a protein that might get it into the nervous system more effectively. The New York Times article describes in rich detail the campaign Kathy orchestrated to make Iplex available, despite the lack of FDA approval or evidence - other than anecdotes from Italy, where the government provides it - for its effectiveness.

There are currently no effective treatments for ALS. It is regarded as a uniformly fatal condition. The desperate effort on the part of ALS patients and their families to try any approach about which they have hope is totally understandable. The public policy challenge is - how should a health system respond to patients in a "last chance" situation who want medications (or other interventions) they regard as promising but which have not been shown to be effective?

It's possible that the medication may prove to do more harm than good, but I don't see that as a reason to forbid access. As Kathy Thompson said when safety concerns were invoked - "what, exactly, is safe about ALS?" Patients who are competent to make decisions and who are fully informed about the risks and benefits of a treatment are entitled to decide whether they want to bear the risks for the chance of the gain.

The core issue involves considerations of the common good. If unproven medications are made available, patients in last chance situations will want to try them. I know that I would. But when this happens it is impossible to find out whether the medication really works. In the 1990s many states mandated insurance coverage for high dose chemotherapy and bone marrow transplant for women with advanced breast cancer. The availability of the treatment made it almost impossible to test its effectiveness. When results finally came in it emerged that the treatment was no better than the existing interventions, and often worse. Hundreds of millions of dollars were spent for what, on a population basis, was a net decrement in health compared to alternatives. (The chemotherapy story is told in detail in False Hope.)

As I read the story I thought - the FDA should make the drug available for what is called "compassionate use," but only in the context of a clinical trial. To my surprise and pleasure, that's exactly what the FDA did in March of this year. Here are the key sections of the FDA statement:

FDA's Decision

The FDA and Insmed [the manufacturer of Iplex] have agreed that access to Iplex for investigational use in patients with ALS will occur in two ways under Investigational New Drug applications (INDs):
1. Single-patient INDs requesting “compassionate use” of Iplex for treatment of named patients with ALS, received and date-stamped by FDA’s document room by close of business on March 6, 2009, will be allowed to proceed, and Insmed has agreed to supply Iplex to those patients; and
2. The remaining supply of Iplex, which is very limited, will be used by Insmed to conduct a clinical trial under an IND in which other patients with ALS who are interested in receiving Iplex treatment will be randomly assigned to receive drug through a lottery system.
All patients who receive Iplex under either a single-patient IND or in the Insmed clinical trial must be adequately informed by their treating physician of the possible benefits and risks of the treatment...

Rationale for FDA's Decision

...FDA has attempted to balance the needs of individual patients who are desperately seeking treatment options for this devastating disease with the need to learn if the drug is in fact beneficial, or harmful, in treating patients with ALS. These considerations were weighed over the last few weeks by FDA scientists and physicians, who held a series of meetings with Insmed and internal meetings to discuss the best path forward.

Conclusion

The FDA understands that ALS is a fatal disease with limited to no treatment options. We are very sympathetic to the desperate situation of patients with this terrible disease, and their families, and we remain committed to facilitating the development of effective drugs to combat ALS. Sometimes therapies that appear promising in the preclinical phase (before studies in humans) do not lead to benefits in patients...

The FDA is mindful of the need to strike a balance between access to unproven therapies for patients with limited treatment options, and the ethics of subjecting those patients to drugs with unacceptable risks or unconfirmed benefits. Today we have chosen a means to provide access to Iplex to as many patients as possible, consistent with all of the considerations discussed earlier.

The FDA has done an impressive piece of ethical analysis with regard to Iplex and ALS. It recognizes the dire circumstances of people like Joshua Thompson in last chance situations, the intensity of society's wish to rescue identifiable victims, and the importance of rigorous evaluation of new treatments on behalf of the common good. Hat's off to the FDA!

Creating a Culture of Research

I recently came upon a terrific article - "Creating a Culture of Research" - that lays out a strategy aimed at making it easier to do scientifically (and ethically) sound clinical research. I write about it here because while its focus is on research, the article has significant implications for organizational ethics in health care.

The authors, Andy Avins and Harley Goldberg, are both associated with Northern California Kaiser-Permanente. Here's the core of their vision:

Perhaps the most important aspect of change is the need for clinical research to be seen as the enormous social good that it is. By providing the knowledge base that establishes effective prevention and therapy, research participants (often by assuming some amount of risk) provide a gift that transcends the simple scientific aspects of their contributions. Yet, unlike many other members of our society who contribute to the general good, these individuals are rarely recognized for their commitment. Similarly, knowledge of the research process is probably very low among the lay public...Such circumstances contribute strongly to the difficulty in recruiting participants to important research investigations. It is time to take a public-health approach towards confronting these issues directly.

Creating a culture more conducive to clinical research requires actions in several domains:

• As mentioned in the above quotation, the public must see participation in clinical research as a contribution to societal well-being. Charitable gift-giving is strong in the U.S. Participation in clinical research is like making a gift to the heart fund a hospital.


• Clinicians must see supporting clinical research as part of their professional responsibility. We ask clinicians to provide evidence-based care. Without their help evidence won't be created.


• Health plans and large health care organizations benefit from evidence about clinical effectiveness. This creates "a special responsibility to become partners in this process and contribute to this agenda."


• Researchers must make participation in research more feasible for patients and clinicians. And, to an even greater extent than when the article was published two years ago, "research participants are entitled to the expectation that those designing and carrying out research protocols are free from suspicious conflicts of interest."

Preaching about the importance of scientifically and ethically sound clinical research won't enhance the research process - a concerted campaign will be required. Unfortunately, the flood of revelations about suppression of negative results in commercially sponsored research and corruption of medical judgment makes fostering a culture of research much more difficult.

I agree with Avins and Goldberg about the importance of strengthening the clinical research enterprise. And from the perspective of ethics I like the potential impact of their ideas on (a) the doctor-patient relationship and (b) health care organizations.

In my writing, teaching, and in this blog, I've often sounded off about the degree to which we underattend to population interests in our approach to health care ethics. In teaching and in the media we focus on the numerator (the individual) but largely ignore the denominator (the population the individual is part of). This myopic approach to ethics encourages selfishness (as if only the individual matters) and social irresponsibility (as if collateral damage from our overly individual-centered system - like our high uninsurance rate - doesn't matter).

In encouraging clinicians and patients to see themselves as collaborators in supporting the advance of medical knowledge we're encouraging them to add a sense of social responsibility to the guiding ethic of care and to recognize the limits of what we know. These would be salutary changes.

With regard to health plans, hospitals and medical groups, the perspective Avins and Goldberg argue for invites all participants in health care to recognize that we have a shared responsibility to contribute to generating the evidence required for "evidence-based practice." This outlook urges us to make the organizations we are part of true learning communities.

A campaign to create a culture of research as envisioned by Avins and Goldberg would have a constructive effect on the ethics of our health system as well. I'm ready to sign on!

Research Ethics - Informed Consent for Cluster Randomized Trials

When we make choices in life we compare alternatives with regard to their quality and cost in virtually every area - except for health care! Our systematic failure to consider value in governing our health care system is a central reason that costs have rocketed out of control.

Randomized controlled trials (RCTs) are the gold standard for evidence, but they are very costly and time consuming. And because the populations enrolled in RCTs must be carefully specified and the settings in which the studies are conducted are themselves not typical, it is often difficult to extrapolate results from RCTs to ordinary practice situations.

So what can we do to get more information about the relative quality and cost of different health interventions?

Imagine the following situation. A and B are widely used treatments for a common condition. While clinicians and patients may have preferences for one or the other, by Freedman’s well-known criteria a state of clinical equipoise exists with regard to A and B – i.e.,- “there is no consensus within the expert clinical community about the comparative merits of [A versus B].”

In order to gain information about the relative effectiveness of A and B several health plans agree to participate in a Cluster Randomized Trial. Some health plans will favor A; the others will favor B. “Favor” means that unless clinicians have specific reasons for choosing the non-preferred agent they will use the preferred one. The health plan data bases will be used to follow patterns of side effects, medication changes and clinical outcomes.

This intervention does not require all individuals to receive the treatment to which their group is assigned, only that the fractions treated with A and B in the two groups differ by a substantial amount. Such separation allows estimation of population-level difference in outcomes, which can inform overall treatment strategies (“in general A and B yield similar outcomes,” or “in general people treated with A fare better”).

I recently joined with a group of colleagues to examine the ethics of this kind of drug trial. We (a) interviewed health plan patients, their physicians, and health plan administrators, (b) discussed CRTs with the Harvard Pilgrim Health Care Ethics Advisory Group, and (c) systematically reviewed the relevant ethics literature. We published our conclusions in a Hastings Center Report article - "Comparing Drug Effectiveness at Health Plans: The Ethics of Cluster Randomized Trials." We focused on two large questions - (a) is individual informed consent required for participation in the kind of trial we envisioned and (b) if it is not required, what takes its place?

We concluded that individual informed consent is not required for participation in CRTs of widely used standard treatments that are in a state of equipoise. If a physician believes that the non-preferred agent is indicated she can prescribe it. If a patient wants the non-preferred agent she can receive it. Practicing physicians are familiar with the state of “internal equipoise” in which they would be equally comfortable recommending one agent or another. A CRT of the kind we envisioned simply asks the physician to prescribe the preferred agent unless she has a specific reason for prescribing the alternative. There is nothing in this chain of steps that is inherently different from ordinary practice. With regard to the prescribing of A or B there is no “experiment” being done and nothing requiring informed consent beyond what is ordinarily required in clinical practice.

Not surprisingly, the U.K., which insures the entire population through its National Health Service, and which faces explicit trade-off questions on a daily basis, has paid more attention to the ethics of comparative effectiveness research than we have in the U.S. In 2002 the Medical Research Council published "Cluster Randomized Trials: Methodological and Ethical Considerations. "Here's the essence of what it had to say about informed consent:

An individual body, or mechanism that can represent the interests of the cluster is required – for convenience this will be labeled the “cluster representation mechanism” (CRM). The appropriate nature of the CRM will vary depending on the circumstances – both the nature of the cluster and the nature of the intervention. Thus, agreement to fluoridate the water supply might be obtained by plebiscite, while GPs might agree to the distribution of an information leaflet to people in their waiting rooms...The CRM must produce a formal document for the cluster that certifies and sets out its ability to [consent] (sufficient knowledge of the circumstances, beliefs, and values of members of the cluster, any delegated authority from/for the cluster, lack of conflicts of interest)...The CRM has essentially the same rights as a patient in an individually randomized trial --- including the absolute right to withdraw the cluster, without adverse impact on the cluster, if it decided that the study was not now in the interests of the community.

We agreed with this analysis.

Our interviews with patients, however, showed that some were perplexed by the idea of clinical equipoise. These patients believed that their doctors knew what was best for them. The idea that large swaths of medical practice do not have an evidence base showing that alternative A is better than B was foreign to them.

Conducting comparative effectiveness CRTs of the kind we envision would involve explicit acknowledgement of the degree to which important areas of medical practice are not evidence based. While we did not see individual informed consent as required for conducting this kind of CRT, we recognized that participation in research is not a typical health care activity. Just as teaching hospitals are expected to make clear that they are replete with students and to explain why this is so and what it might mean to patients, we believe that health plans and medical organizations should do the same with regard to participation in research - even research that does not require individual informed consent.

Information about comparative effectiveness is a necessary condition for getting a better grip on our health care system, but it is not sufficient. The more difficult step will be having the guts to use the information we develop.

In addition, those who lead the effort to strengthen comparative effectiveness research will have to educate the public about why the research is so important. The U.S. public has a strong faith in medical science and a rapacious appetite for medical miracles. Transforming our delivery systems into true learning organizations will require open recognition of medical uncertainty in ways that are not often acknowledged by physicians or understood by patients. But using everyday medical practice as a source of systematic learning about treatment effectiveness would be a salutary change in the culture of medical care.

Should the NIH Alternative Medicine Center be Defunded?

I only became aware of the controversy about the National Center for Complementary and Alternative Medicine (NCCAM) from an article in this morning's Washington Post - "Critics Object to 'Pseudoscience' Center."

In 1992 Congress allocated $2 million to establish an Office of Alternative Medicine (OAM) at the National Institutes of Health "to investigate and evaluate promising unconventional medical practices." In 1998 NIH Director Dr. Harold Varmus proposed having all alternative medicine research done through the NIH institutes, with the OAM coordinating the process. Senator Tom Harkin (Iowa), who pushed for the founding of the OAM in 1992, now pushed through legislation that elevated its status to that of a Center (NCCAM). Current funding is approximately $120 million.

The current controversy was launched on January 15 by a posting on the website the Obama administration created during the transition to solicit ideas:

Biomedical research funding is falling because of the nation's budget problems, but biomedical research itself has never been more promising, with rapid progress being made on a host of diseases. Here's a way to increase the available funding to NIH without increasing the NIH budget: halt funding to NCCAM, the National Center for Complementary and Alternative Medicine. This Center was created not by scientists, who never thought it was a good idea, but by Congress, and specifically by just two Congressmen in the 1990's who believed in particular "alternative" (but scientifically dubious) treatments. Defunding NCCAM would save at least $225 million, possibly more.

...Any legitimate, promising medical treatment can be funded by one of the existing NIH Institutes. There's no need for a separate center for "alternative" therapies - but what has happened is that NCCAM has become a last refuge for poorly designed, unscientific studies that couldn't get funded through the normal peer-reviewed process.

Senator Harkin's comments, intended to support NCCAM, only make the Center look worse:

"One of the purposes when we drafted that legislation in 1992 . . . was to investigate and validate alternative approaches. Quite frankly, I must say it's fallen short. I think quite frankly that in this center, and previously in the office before it, most of its focus has been on disproving things, rather than seeking out and proving things."

The idea that the Center's role is to validate faith-based health beliefs shows a deep misunderstanding of science. If the Center has a role it is to test hypotheses, not to validate faith.

But the controversy over NCCAM isn't new. In the early 20th century organized medicine was horrified by the growth of Christian Science. Wise physicians recognized that the emergence of Christian Science reflected a sense that something was missing in "conventional" medicine. That hunger is still present. More than 1/3 of U.S. adults use "alternative" medicine techniques.

This enthusiasm proves nothing about effectiveness. But it does point to phenomena that warrant serious scientific study. Otherwise the field will be ceded to quacks and hucksters, in the tradition of Mark Twain's Duke and Dauphin, selling snake oil.

I don't have a sense of how well NCCAM has carried out its mission, but some of its goals seem right on target, as exemplified by:

* Identify the common and specific features of widely used mind-body medicine practices
* Determine the extent to which patient expectations prior to treatment and satisfaction following manipulative and body-based practices are related to objectively measured biological endpoints
* Enhance understanding of the social, cultural, and economic factors relating to the use of CAM.

But there is a worrisome ambiguity in other goals:

* Establish the efficacy of selected biologically based practices to maintain health, prevent disease, and treat conditions of public health importance
* Document the benefits of some CAM whole medical system treatments for selected health conditions

Is the aim here to evaluate whether specific widely used techniques are effective and provide benefit, or to "prove" that public beliefs in these techniques are indeed true?

If it's the latter, NCCAM should be defunded. But insofar as it undertakes serious evaluations of widely used techniques, and studies just what is happening when patients derive significant subjective benefit from techniques that are not validated in controlled trials, NCCAM will be making a worthwhile effort.

In voting with its money and time the public is saying it feels healed by alternative techniques. The mechanisms of healing are worthy of scientific study, just as the mechanisms of disease are.

Comparative Effectiveness Research

"Health Care and the American Recovery and Reinvestment Act," an article today's New England Journal of Medicine, should be read by anyone who has not been following the arcane details of the U.S. stimulus program.

The part of the article I want to focus on in this post is funding for comparative effectiveness research (CER). I've put my comments in bold italics:

On the medical research front, comparative effectiveness studies that directly compare the risks and benefits of different treatments for a particular condition are essential for improving practice and slowing cost escalation. Such studies, however, have been controversial; the pharmaceutical and medical device industries may not fund them, and some are concerned that the government or insurers may use the results to mandate specific approaches to treatment or to deny coverage.

I don't believe there is much public concern about CER. In every other aspect of our lives we compare the effectiveness and relative value of the options we must choose among. We also make personal rationing decisions every day when we decide that our resources require us to forgo a benefit - perhaps just a Latte at Starbucks, but possibly attending a lower cost college than our more costly first choice.

We are already seeing, however, a fear-mongering campaign against CER. Harry and Louise haven't come back yet but they will soon be reincarnated as the bogeyman of a "government bureaucrat getting between you and your doctor." More subtly, we will also see efforts to block research on the cost component of CER and to insert regulatory language that forbids Medicare to make use of CER in its coverage decisions!

...With the money allocated in the stimulus bill, the government will be able to fund many more [CER] trials, as well as clinical registries, clinical data networks, and systematic reviews. Indeed, the $1.1 billion in new funding for comparative effectiveness research dwarfs the current $334 million annual budget of the Agency for Healthcare Research and Quality, which will administer $300 million of the funds; the NIH and the DHHS will administer the rest.

We shouldn't expect CER to drive sensible health coverage on its own - that will require active, and often courageous, management and leadership. But as more and more studies are done an embarassment factor may set in for advocates who plead for expenditure of collective funds (public and private insurance) on costlier alternatives.

In addition, the act includes funds for a contract under which the Institute of Medicine will make recommendations (by June 30, 2009) for “national priorities for comparative effectiveness research.” It establishes a Federal Coordinating Council for Comparative Effectiveness Research, which will be composed of up to 15 federal officials (at least half of whom are physicians or others with clinical expertise) and chaired by the secretary of health and human services. The council will be tasked with recommending and coordinating research but will not be able to establish clinical guidelines or to “mandate coverage, reimbursement, or other policies for any public or private payer.

If the Federal Coordinating Council doesn't get hijacked by industry it has the potential of becoming an honest broker and public educator, much as has happened over time with the Federal Reserve. And having three agencies administer CER funding may make it more difficult for commercial foxes to capture the public chicken coop!

Comparative effectiveness research may seem like a wonky topic, but it is central to improving the disgraceful state of our health care "system." The president understands this. I hope that he will bring his superb communication skills to bear on educating us about the common sense validity of using CER to guide health care and the moral and fiscal necessity for doing this.

As a poignant lesson about what is at stake globally for health care, the article I've quoted is immediately followed by "A Lion in Our Village - The Unconscionable Tragedy of Cholera in Africa." A tiny fraction of the funds that produce no benefit at best and harm at worst could save thousands of lives elsewhere in the world!

Ethics in Time of Financial Crisis

Nancy Walton, lead author for the Research Ethics Blog had an excellent post yesterday about "Ethics on the chopping block." She reports on proposals to end ethics program at the University of Memphis in Tennessee and in New Zealand, and argues - correctly I believe - that ethics programs are more important during a financial crisis, not less.

Here's her key conclusion:

Ethics review boards, in either academic or medical settings, should be doing more than reviewing protocols, providing approvals and monitoring ongoing research in a silo somewhere, unconcerned that these kinds of cuts, as they don't name "research ethics" explicitly, have nothing to do with them. While reviewing research takes up a tremendous amount of time and energy, as I well know chairing an ethics review board myself, there is a certain amount of advocacy, outreach and education that an ethics review board must be committed to doing, on an ongoing and iterative basis.

This is right on. When my own organization experienced a major financial crisis in late 1999 many painful cuts were made, and I expected that our ethics program might be among them. Instead the COO gave our Ethics Advisory Group a special assignment - recommend a framework of values for dealing with the crisis. He said - wisely - "it's fine to say we endorse five values, but when we have to make tough choices we have to set priorities among them..."

Ethics programs can't solve financial problems by printing money, but they can contribute guidance about how to deal with the crisis in ways most consistent with mission and core values.

Health Care Rights in India and the U.S.

In yesterday's post on "Drug Marketing in Mumbai" I mentioned that I'm reading ethics literature from India in preparation for a visit I'll be making soon.

In the most recent issue of the Indian Journal of Medical Ethics, Dr. Helen Sheehan from the South Asia Studies Department at the University of Pennsylvania has a fascinating article on "Cancer, access to investigational drugs, and patient rights in the USA and India."

Dr. Sheehan tells a story from the U.S. (the Abigail Alliance case, which I discussed in "Access to Experimental Drugs - the Supreme Court Gets it Right") and a story from India (a cancer drug trial carried out at the Regional Cancer Center in Thiruvanathapuram in Kerala).

What's most striking in the story is that the rights at stake are polar opposites. Interestingly, both situations involve Johns Hopkins.

The Abigail Alliance case was brought on behalf of Abigail Burroughs, a young woman who contracted a rare head and neck cancer that did not respond to standard treatment. Her Johns Hopkins physician wanted to give her an experimental medication, not yet approved by the FDA. The legal action claimed a right for dying patients to have access to experimental drugs. The drug was not made available. Abigail died in 2001. The drug was subsequently approved by the FDA.

The posthumous appeal claimed a constitutional right to the drug, based on the fifth amendment guarantee that no person shall “be deprived of life, liberty, or property, without due process of law.” Patients in “last chance” situations, when standard treatment offers no hope – are facing death. The Abagail Alliance argued that by not facilitating access to drugs that have passed through Phase 1 trials, the FDA is depriving them of the right to opt for a potentially life-saving intervention. The District of Columbia Circuit Court ruled against the Alliance.

The situation at the Regional Cancer Center in Kerala involved trial of an experimental drug on 27 oral cancer patients from November 1999 to April 2000. The agent had only been tested in mice. Without approval from any IRB, a scientist from Johns Hopkins contracted with the Regional Cancer Center and brought the drug to India. In July 2001 a physician at the Regional Cancer Center blew the whistle on the study, claiming that no approval had been given and that the informed consent process was a sham. Johns Hopkins conducted its own investigation and concluded:

* The scientist was negligent for failing to submit a proposal for the clinical trial to a Johns Hopkins University institutional review board. Under university policy and federally mandated procedures, faculty experiments involving human subjects must have prior IRB approval, whether conducted in the United States or abroad.

* The trial did not meet Johns Hopkins standards for research with human subjects. For example, the committee found there was inadequate safety testing of the drugs in animals before they were injected into human patients. The committee also said that consent forms used to recruit patients for the study were inadequate.

* The scientist carried drugs used in the study to India without either an "investigative new drug" approval from the Food and Drug Administration or explicit FDA export permission.

* The scientist, without authority, signed several versions of a document committing the university to collaboration with the RCC.

In the U.S., the Abigail Alliance claimed (unsuccessfully) that the FDA regulations were too strict and abrogated Abigail's rights by preventing her and her physicians from protecting her against avoidable death. In India critics concluded that the Regional Cancer Center was too lax in its oversight of research, and that the drug trial abrogated participants' rights to adequate protection.

It isn't surprising that a country with strict research regulations (the U.S.) pushes drug research to sites where the regulation is more lax (such as India).
A New England Journal article discusses the risks to India as "A New Colonialism."

I hope we are in the process of seeing a global re-equilibration with regard to "rights" in health care. In the U.S. our expectations are excessive - as evidenced by our belief that we have a right to anything we or our doctors hope might provide benefit. In India, at least as seen by an outsider, expectations for what each individual deserves are too low, as evidenced by the way poor patients at the Regional Cancer Center were herded into a study. The disputed drug trial in India reflects the dark side of both countries - U.S. entitlement to join in the exploiting of poor citizens in India.

We owe thanks to the whistleblowers and journalists who give both countries opportunity to look in the mirror and see our failings.

Senator Grassley, Psychiatric Ethics, and Conflict of Interest

Senator Charles Grassley, ranking Republican on the Senate Finance Committee, is on the warpath about conflict of interest in psychiatry.

More power to him. My profession and the public should thank him and his staff.

Senator Grassley and his committee have pursued conflict of interest inquiries for many academic leaders in psychiatry - most recently Dr. Charles Nemeroff, who, until he stepped down this week, was chair of psychiatry at Emory.

In each case the issue is essentially the same: (1) the psychiatrist in question was paid substantial sums by drug companies; (2) the psychiatrist in question wrote, spoke and did research about the company's products; and (3) the psychiatrist's disclosures of the financial arrangements were incomplete at best and, possibly, deliberately inaccurate.

The basic response has been, essentially - "my judgment has not been corrupted, trust me."

This isn't adequate, and neither is disclosure.

For contrast, take an area of psychiatric ethics about which the American Psychiatric Association is unambiguous - "sexual activity with a current or former patient is unethical." Why is this the case?

The most common rationale is that the patient will be harmed. This is probably true almost all the time. But there are well known examples of decades long happy marriages between psychiatrists and former patients. Why don't these examples undermine the absolute ethical prohibition?

The reasons are (1) trust and (2) the ancient roots of the medical profession in religious healing. When we're ill we turn to members of the health professions. As professionals they "profess" basic commitments, most notably, that they will always seek our well-being and will not exploit us. Even if there have been some happy marriages between psychiatrists and former patients, any ambiguity about the attitudes and values on something as basic as having sex with their patients will diminish overall trust in a profession we count on when we're in some of life's toughest moments. Medicine won't work if patients have to wonder if the physical exam is leading to diagnosis and treatment or to sex.

Just so with the revelations about Dr. Nemeroff. Even if his research papers are scientifically impeccable and his clinical recommendations have been unbiased, the revelation that he earned $2.8 million from drug company consultation between 2000 - 2007 (and failed to report at least $1.2 million) undermines the trust the profession needs.

Medicine needs to reformulate the way it manages conflicts of interest. Disclosure is necessary, but it's not sufficient, even if it is done well. (And from Senator Grassley's inquiry we know just how poorly it's actually done.) The expectations will be more complex to articulate than "no sex with current or former patients," but we need better behavioral guidelines as to what is acceptable and what isn't.

(If you want more on this topic, see articles in the New York Times and Wall Street Journal, and Senator Grassley's October 2 letter to Emory. And, see previous posts here and here.)

Genomics, Google, and Medical Ethics

The topic for the next meeting of the Harvard Pilgrim Health Care (a not for profit health insurer in Massachusetts, New Hampshire and Maine) Ethics Advisory Group, which I chair, is "Anticipating the Ethical Challenge of Genomic Medicine." I've been reading and thinking about what genomic medicine will mean for health plans for the past few weeks.

Yesterday, Sergey Brin, co-founder of Google, wrote in his blog about finding that he has a genetic mutation that increases the likelihood that he will develop Parkinson's Disease. I've quoted his wonderfully lucid posting below (in italics), followed by observations about some of the ethics and policy implications of his comments:

"For more than 20 years, my mother has worked with computers at NASA. So, when she developed a pain in her hands the diagnosis seemed easy -- Repetitive Stress Injury. Except that it wasn't so easy. As her mysterious symptoms progressed it varied -- RSI, fibromyalgia (unexplained pain), Lyme Disease, and so forth. It was only after visits to many specialists over a number of years that the diagnosis settled -- Parkinson's Disease. Since there is no clear test for Parkinson's -- it is defined by its symptoms -- we only grew certain as those symptoms developed and as her medications began to alleviate them."

What Mr. Brin's mother experienced is common in medicine - significant symptoms with no clear cause. As often happens, she saw many specialists and many different diagnoses were made. Happily, it does not appear that she went through a period of being "blamed" for her symptoms, as by "imagining" them or being "too sensitive to normal pain."

My mother had always been haunted by Parkinson's because her aunt had suffered from it. I had often reasoned with her that since Parkinson's is not hereditary (there is not a strong correlation of Parkinson's incidence among close relatives), she had little to fear.

Many people, perhaps most of us, are "haunted" by images of our future derived from experiences in our families. Mr. Brin's responses to his mother were based on the best information available at the time. But as emerges below, new facts emerged.

"In 2004, my wife, Anne, introduced me to her future cofounders in 23andMe as they were studying the genetics of Parkinson's Disease. As with my mother's fear, I was skeptical about the study. I reasoned that if there was much to be learned about Parkinson's in the genome, there would have to be a high percentage of inherited cases. In fact, I appeared to be right in that this particular study did not bear immediate fruit."

23andMe is a harbinger of the future - one of the new "personal genetics" enterprises that will provide genomic analysis directly to individuals who submit biological samples, typically saliva (23andMe sends a "spit kit"). How these services will be used and how individuals will react to and use the results are questions we won't know about until more experience accumulates.

"Nonetheless, there are some cases of familial Parkinson's but they are quite rare. Over the past few years researchers have been honing in on the genes that are responsible for those cases. One gene that stands out in those studies is LRRK2. There is one particular mutation of the LRRK2 gene -- known as G2019S -- that, while rare even among people with the disease, accounts, in some ethnic groups, for a substantial proportion of familial Parkinson's.

As a customer of 23andMe, I have always been excited about the product. I have found what pieces of DNA I share with various relatives. I checked whether other Brins were related. I explored my various gene journals -- learning, for instance, that I have one copy of the fast twitch muscle fiber. I also looked over the health related entries and found that my genetic risk for most diseases is modestly lower than average but for a few diseases it is modestly higher.

Because there are only a small number of genes which are known to have a very substantial effect on health (e.g. 10 times the average risk), I felt the possibility of discovering something very important to my health was just a hypothetical exercise. So, when my wife asked me to look up G2019S in my raw data (23andMe scientists had had the forethought to include it on their chip), I viewed it mostly as entertainment.

But, of course, I learned something very important to me -- I carry the G2019S mutation and when my mother checked her account, she saw she carries it too.

The exact implications of this are not entirely clear. Early studies tend to have small samples with various selection biases. Nonetheless it is clear that I have a markedly higher chance of developing Parkinson's in my lifetime than the average person. In fact, it is somewhere between 20% to 80% depending on the study and how you measure."

As a customer of 23andMe, Mr. Brin, not surprisingly, is stunningly well informed and logical in his thinking. If all users of the new, entrepreneurial genomic services were as sophisticated as Mr. Brin, concerns like those expressed in a January New England Journal of Medicine article - "Letting the Genome Out of the Bottle - Will We Get Our Wish?" would vanish.

"This leaves me in a rather unique position. I know early in my life something I am substantially predisposed to. I now have the opportunity to adjust my life to reduce those odds (e.g. there is evidence that exercise may be protective against Parkinson's). I also have the opportunity to perform and support research into this disease long before it may affect me. And, regardless of my own health it can help my family members as well as others.

I feel fortunate to be in this position. Until the fountain of youth is discovered, all of us will have some conditions in our old age only we don't know what they will be. I have a better guess than almost anyone else for what ills may be mine -- and I have decades to prepare for it."

Mr. Brin is an ideal user of genomic services. He interprets the findings as well as could be hoped for. He has deep intellectual curiosity. He responded to the bad news about the G2019S mutation in a profoundly constructive manner: (1) He considers what he can do to reduce the risk; (2) His wealth allows him to support research, which might benefit him directly, but will also contribute to the public good; (3) He puts the news into perspective - there is no fountain of youth and we will all encounter significant health problems in our lives; and, (4) He shows emotional resilience, and uses the news as an opportunity to "prepare" rather than despair.

There are, however, less happy scenarios that can be imagined. Here are two. (1) From my experience as a psychiatrist it is not hard to picture someone less resilient than Mr. Brin, perhaps subject to depression, who would take this kind of news as a death sentence, and perhaps even become suicidal. (2) In light of how costly health insurance is, it is not hard to picture people testing their genomic pattern with the idea of going without insurance in the absence of major risks and becoming heavily insured if the predicted risks are great. For individuals this is rational behavior, but in the fragmented U.S. health system this information asymmetry could ultimately undermine the insurance process. (Interestingly, the increasing availability of genomic information might give a push to the single payer option. Only if everyone is in the system is there is no advantage to using genomic information to game it!)

Access to Experimental Drugs - the Supreme Court Gets it Right

Today’s Los Angeles Times reports that the Supreme Court has turned down an appeal that claimed a right for dying patients to have access to experimental drugs not yet approved by the FDA. The appeal was brought by the Abigail Alliance, founded in memory of Abigail Burroughs, a beautiful young woman whose picture is on the website. Abigail got a rare head and neck cancer in 1999. Her Johns Hopkins physician wanted to give her an experimental medication, but was not able to. Abigail died in 2001. The drug subsequently received FDA approval. A short, powerful statement of the Abigail Alliance’s argument is in the January 11 Wall Street Journal.

The constitutional right the appeal argued for is based on the fifth amendment guarantee that no person shall “be deprived of life, liberty, or property, without due process of law.” Patients in “last chance” situations, when standard treatment offers no hope – are facing death. The Abagail Alliance argues that by not facilitating access to drugs that have passed through Phase 1 trial, the FDA is depriving them of the right to opt for to a potentially life-saving intervention.

As heartbreaking as it is to contemplate the death of 21 year old Abigail Burroughs and others like her, I think the Supreme Court got it right, for four main reasons. The court recognized the first two:

* The appeal argued for a terminally ill patient’s right to weigh the benefits and risks of taking the experimental medication and to pay for it with their own means. But Phase 1 testing does not provide the kind of information required for truly informed physician recommendation or patient consent, especially in desperate circumstances. The public, through the FDA, has a legitimate interest in the public safety implications of the FDA restrictions.

* Substantially unfettered access to experimental medications would severely undermine the ability to conduct rigorous controlled trials. Patients would be much less willing to enter a double blinded study if they could get access to the experimental agent by another route. Here too, the public has a legitimate interest in fostering rigorous testing of proposed new treatments.

* Although the appeal was limited to drugs in last chance situations and required self payment for access, there is every reason to expect that public and private insurance programs would soon be asked to cover the cost, and that patients with serious but not terminal conditions would press for the same kind of access. The cost of health care is already causing serious harms through uninsurance and job loss from diminished economic competitiveness. The public has a legitimate interest in mitigating the harms caused by runaway cost increases.

* Finally, the appellant’s argument would add to public confusion about the difference between evidence-based treatment and wishful thinking about experimental agents. Our health system is already permeated by magical thinking and denial of death. As well-intentioned as the appeal is, it would add to this unfortunate aspect of U.S. culture.

(For those with time and inclination to read a 22 page document, the decision of the District of Columbia Circuit Court, which the Supreme Court upheld by declining to hear an appeal, makes fascinating reading.)

Guinea-Pig Ethics

Carl Elliott’s excellent article on “Guinea-Pigging” in the forthcoming January 7 New Yorker (only the abstract is available on-line) educated me about a topic I should have known about already – the inner workings of pharmaceutical contract research organizations.

Over the past decade, pharmaceutical companies have increasingly outsourced the conduct of clinical trials to contract research organizations. CROs are big business. Revenues are estimated at close to $18 billion. The largest 10 firms enrolled more then 640,000 subjects in trials in 2004.

“Guinea-Pigging” is the insider term for the job of research subject in a CRO project. This isn’t volunteering from altruistic motives as patients of mine with HIV and cancer have done to contribute to scientific progress in an area they care about. It is a job, and not an elevated one. A guinea pig for a sleep study described the work as a form of prostitution – “I would sell my body not to slobbering johns who assail the street whore with their unkempt organs, but to slick, white coated neuropsychologists who use thrice sterilized catheters, electrodes…and invasive thermometers to get what they want.”

Readers who, like me, do not yet know in any detail about the recruitment of healthy subjects for CRO studies can visit Guinea Pig Zero, defined as a "jobzine for people who are used as medical or pharmaceutical research subjects." And, as well, websites for large CROs, such as Pharmaceutical Product Development, Charles River Laboratories, and Covance.

CROs are at the heart of the development of new treatments, but they have largely been under the radar in terms of recognizing just how important they have become. Subject recruitment is becoming a worldwide industry. I look forward to learning more about the area in the next few months. We owe Carl Elliott thanks for bringing questions about the ethics of the role -- safety, compensation, and non-exploitation, to the fore.

Research Ethics and Quality Improvement

By chance, as I was writing about Atul Gawande’s New Yorker article about checklists for yesterday’s posting, the Sunday New York Times arrived with his Op Ed piece about how the Federal Office for Human Research Protections has put the project on hold for lack of informed consent from patients and clinicians.

Today I reviewed the letters sent to the research team at Johns Hopkins by OHRP on July 19 and November 6. It looks to me as if the OHRP has followed the letter of its regulations, while entirely ignoring the spirit of its mission. The letters cite numerous details that indicate that research was being done. Luckily, it was. The Johns Hopkins team was studying, in a rigorous manner, the impact of an effort to systemize good clinical care. The question was not whether an experimental drug helped or hurt research subjects, but whether a disciplined managerial approach to doing what we know is the right thing to do produced measurable improvements.

If Kristina C. Borror, Ph.D., Director of the Division of Compliance Oversight at OHRP, who wrote the letters to Johns Hopkins, reported to me, this is what I would have said:

“The purpose of our office is to protect people in the health care system. The checklists aren’t research. They are part of a managerially sophisticated effort to make ICUs accountable for doing what all ICUs agree should be done, in order to protect people in the health care system. It is great that Johns Hopkins is studying that care management process. Please show them how their application could be corrected so that we don’t erroneously subject the project to a misguided requirement for individual informed consent.”

In 2006 the Hastings Center published an excellent report on “The Ethics of Using QI Methods to Improve Health Care Quality and Safety.” The conclusions are sensible, well thought out, and practical. None of the conclusions would require individual informed consent from patients or ICU staff:

* QI is any systematic, data-guided activity that is designed to bring about the immediate improvement of care in a local setting.
* QI is both appropriate and vital to health care.
* QI is marked most distinctly by the prompt feedback of the effects of deliberate changes to the same care delivery setting that is making the changes.
* QI is intrinsic to health care delivery and obligatory for both professionals and patients.
* Though QI is often driven by a priori evidence that suggests substantial benefits are likely for the patients and/or staff involved, QI can pose some risks to some
patients.
* Not undertaking QI in the face of recognized quality deficiencies also puts patients at risk.
* QI should itself be implemented ethically.
* Low-risk QI should generally have the same review and standards as routine health care delivery.
* Higher-risk QI should undergo routine and orderly review within the usual arrangements for clinical supervision or by an advisory group.
* Some projects are correctly counted both as QI and as research involving human subjects and should meet the requirements for review of protection of human subjects
in research.
* Meeting those requirements might be more readily accomplished with a QI-IRB that met regulations, but whose policies and procedures were also tailored to the needs and expectations of QI.
* Certain issues might trigger the requirement for formal review of a proposed QI project: randomized designs, novel treatments, involvement of researchers, delayed
feedback of monitoring, or external funding.
* Federal agencies and voluntary organizations should cooperate in further developing and implementing these ideas.

We have had so many examples of the Bush administration subjugating scientific integrity to ideology that it is hard to avoid suspicion about the motives of the OHRP for scuttling the project. But whatever the motivation behind OHRP’s actions, it is important for the agency to reverse course promptly.

A Tipping Point for Pharma Ethics?

Pharma is the Jekyll and Hyde of health care. At their best, drug companies develop research-based treatment breakthroughs and do well by doing good. At their worst, as described in the Senate Finance Committee report on Avandia that I discussed in yesterday’s posting, greed strangles ethics.

A story on the front page of the business section in today’s New York Times leads me to believe that we are approaching a tipping point for Pharma ethics. The headline reads: “After a Trial, Silence – Cardiologists Question Delay of Data on 2 Cholesterol Drugs.” The story describes vigorous pushback from cardiologists against Merck and Schering-Plough for a suspicious delay in reporting the findings from a drug trial and for changing the criteria for evaluating outcomes in midstream.

The doctors who are quoted – including the chief of cardiology at Walter Reed – fear that pharmaceutical companies are, once again, cooking the books. The words “fraud” and “deceit” do not enter the story, but the implication is there.

There is nothing complicated about the ethical issues involved. Either the cannons of openness and scientific honesty are being followed or they are not. What stands out for me is the degree to which the reporter understands that this could be another Avandia or Vioxx story in the making, and how much space the Times devotes to it. The Senate Finance Committee report on Avandia was similarly blunt and hard hitting.

When media, legislators and their staffs, physician leaders around the country, and movies like “The Constant Gardner,” speak in unison, and when liability lawyers are waiting in the wings to hit Pharma with yet another class action suit, we have a powerful force emerging. The lure of blockbuster profits from blockbuster drugs draws out every technique of wild west capitalism, but at this point the pushback is too strong to be chilled out by a public relations campaign.

The pharmaceutical industry has a history and traditions to be proud of. Polls of public trust put pharmacists near the top. The fact that massive profit potential has led to corrupt practices isn’t surprising. But more drug scandals would be bad ethics and bad business, and would irrevocably taint the industry.

I predict that the pharmaceutical industry feeding frenzy is coming to an end. If we are truly at a tipping point we have to thank the whistle-blowers and determined activists who have fought so vigorously for good health system ethics.

Spurious Reasoning about Pharmaceutical Ethics

A recent New York Times Op Ed by Peter Pitts, President of the controversial Center for Medicine in the Public Interest, attacks the idea of federal funding for studies that compare drug effectiveness in terms that will soon show up in drug company lobbying.

In a breathtaking piece of spurious reasoning, Pitts argues that because Medicare would probably not pay for costlier medications if cheaper ones were equally effective – an enlightened and fondly-to-be-hoped-for policy – it is a conflict of interest for the National Institutes of Health and other government agencies to fund comparative effectiveness studies.

It is entirely reasonable to criticize specific comparative effectiveness studies on methodological grounds. That is what science is all about. But Pitts dismisses the very concept of comparative effectiveness studies as “flawed.”

Pitts speaks of “cost concerns” as if caring about cost is the devil’s work. He is dead wrong. To make health care more widely available, to fund other social priorities, and to allow U.S. industries to be more competitive, we need clinically informed, ethically guided health care cost containment. Ethical physicians should join together to set limits on which drugs will be paid for by insurance funds, and to ensure that a robust process for appeals and policy revision is in place.

Pitts argues against cost containment by invoking the bogeyman of Medicare “forc[ing] doctors to prescribe only the drugs that Medicare will pay for — not the ones that are best for the patient.” The implied premise is that whatever any individual physician prescribes is, by definition, what is best for the patient. No informed person really believes this. There is huge variation in prescribing practices. Evidence is one source of prescribing behavior. Patient demand, often fueled by direct to consumer advertising, is another. Drug company sponsored dinners, speakers, seminars, and holidays, is still another.

We can’t leave the key to spending insurance funds in the hands of every individual physician without oversight. That oversight should come from expert medical guidance. Fair process in setting needed limits is what a Center that is truly “for Medicine in the Public Interest” should be lobbying for, not anything goes prescribing.

The fact that the Center for Medicine in the Public Interest is partly funded by drug companies does not invalidate Pitts’s arguments. But the combination of spurious arguments that favor unbridled prescribing and drug industry funding does not pass the sniff test.