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Sunday, April 22, 2012

New and disruptive feedback loops in the research world?

Validation of scientific research findings appears to be getting some traction ....

They identify the Psyche File drawer ( which allows researchers to upload their own results of replication (or attempts thereof) and view the attempts of others.

What if publication of research findings required someone else to validate your findings? What if study sections viewed replication as a critical element?

Earth Day Disconnects

I went to a lecture by a prominent theologian yesterday on the moral underpinnings of modern ecology movement. It is hard to argue with such a basic tenant as the one that was posited: mankind has a moral obligation to be a good steward to the earth. The position is like many moral charges, the devils are always in the details.

The audience attending was very upper middle class and mostly older, with a smattering of families with children. They were mostly "green" being avid recyclers and a few owning hybrid cars. We all live in neighborhoods where the homes are well kept, the trash is regularly picked up, and a state driven recycling system is in place. The environments where we live are substantially cleaner than they were a generation ago. Despite being in an urban area, wildlife populations are exploding with deer and coyote.

I could not help but contrast this to my recent experience in Haiti. In Haiti, there is garbage everywhere. The streams are horribly befouled, with trash, human waste, and likely toxic waste. The messages I take away from these observations underscore a series of paradoxes. Why is abject poverty linked to despoiled environments and what does this have to do with the goals and tactics of the Green movements in affluent western societies?

At the most obvious level, poverty in Haiti results in despoiled environments because those in Haiti do not have the time or resources to place maintaining their environments as a high priority. Humans living on the edge of existence need to deal with their own immediate physical needs followed by the needs of their families. Priorities for most Haitians are finding enough to eat, getting enough water (ideally clean water), and maintaining basic shelter. Energy diverted to deal with secondary priorities represents a poor choice and potentially an actual existential threat. Stated differently, the ability to divert resources to being a good steward of the earth is a luxury which most Haitians simply cannot afford.

Virtually all activities in our affluent world which we identify as being associated with environmental stewardship require energy and wealth. How do those curbside recycling pickups happen? How is human waste handled so as it does not despoil your yard and local streams? All of this requires large infusions of energy and human effort. Until relatively recently in human history, the ability of capture and use energy was very limited and consistently having enough to eat was not a given. Large animals freed humans from some of the back breaking tasks and water power was also used to drive some selected machines. Neither of these energy forms relieved humans of their roles as the primary source of energy and with that reliance came a marginal existence for most of humanity. Until perhaps 500 years ago, virtually all of humanity lived hand to mouth.

My travels to Haiti took me back to that world, a world which reflects the reality of humankind for tens of thousands of years. The Haitians are in some sense very "green". Outside of Port au Prince, their environments are not particularly polluted by automobiles or trucks. They do not need to worry about acid rain from coal fired electrical generation. Each individual Haitian has an exceedingly modest carbon footprint. However, their environments tend to be terribly despoiled. I could discern no wildlife when I was visiting. The hills of La Gonave are essentially stripped of trees, the product of being reliant on charcoal for for fuel. There is trash everywhere, no surprising since there not insufficient resources to deploy to pick it up and take it anywhere more appropriate.

The messages I take away from these contrasting observations are:

1. Good stewardship of the earth requires making humans affluent enough so as they have the resources beyond those required to simply survive.
2. Human poverty is associated with the inability to access cheap energy and activities which make energy more expensive, doom more people to poverty and will result in more environmental destruction
3. The priority we should have is to create environments where people broadly have the tools to bring wealth to themselves and their families through increased productivity and their environments will improve.

Prior to the industrial revolution, the existence of the average person in Western Europe was dismal, likely not any better than the life of peasant farmers in Africa, Asia, or Haiti. The explosion of industry and trade resulted in massive social disruptions including the migration of people to cities. They lived dismal urban existences but this should be viewed within the context of the likely more dismal rural existences their immediate predecessors endured. The industrial revolution resulted in substantial negative environmental impact but over the span of a few centuries, it lifted huge populations out of poverty, not only in Western Europe. These populations are now the populations who have the luxury of begin able to celebrate Earth Day and can continue invest resources to create a cleaner environment. It would be unwise to mandate behaviors which will undermine the economic miracle which permits us to have the luxury of reflecting on such concerns.

Sunday, April 15, 2012

Reconciling Quality metrics and patient choice

As readers of my blog probably realize, I have become increasingly an advocate of data collection and data/metric driven medicine. At this point in my career, I have come to realize that you can't improve if you don't know where yo u are starting from. In order to define baselines you need to measure something(s). In order to develop feedback loops we need to embed data collection into what we do.

I was doing my usual scan of the literature this weekend and I came across an article in the Annals of Internal Medicine looking at the benefits and risks of screening mammography.
Overdiagnosis of Invasive Breast Cancer Due to Mammography Screening: Results From the Norwegian Screening ProgramAnn Intern Med April 3, 2012156:491-499;
Yet again the results of large scale screening fail to demonstrate broad and unambiguous benefits of using mammography to prevent death from breast cancer and appear to result in over diagnosis and over treatment of what appears to be biologically benign disease. In the same issue were a series of letters addressing an earlier study of screening for prostate cancer with PSA with similar results.

The Annals has created a library of patient materials based upon Annals studies and in this issue of the Annals a breast cancer and mammography is also published.

The text is copied below....

What is the problem and what is known about it so far? - Women are advised to get routine mammograms to find breast cancer early, before it would have been noticed on examination. This is called screening mammography. However, some cases of breast cancer found with screening mammography would never have been noticed and therefore would not have led to death.
 Why did the researchers do this particular study? -To see how common screening mammography leads to overdiagnosis of breast cancer.
 Who was studied? -Women in Norway who had a diagnosis of invasive breast cancer from 1986 to 2005.
How was the study done? - In Norway, screening mammography was introduced or “rolled out” over a decade, county by county. The number of cases of breast cancer found in counties with screening was compared with the number of cases found in counties without screening during the same period.
What did the researchers find? - About 15% to 25% of cases of breast cancer found through routine mammography were overdiagnosed; that is, they would never have been found on examination or led to death. 
What were the limitations of the study? - The study included women diagnosed with invasive breast cancer, not those with ductal carcinoma in situ, a different form of breast cancer. The study was not a randomized trial where women were or were not given mammograms depending on chance (like flipping a coin).
What are the implications of the study? - For many women, screening mammography may lead to a diagnosis of breast cancer that would never have been noticed or caused harm during their lifetime. These women would have been unnecessarily treated with therapies, including surgery, radiation, and chemotherapy, that have adverse effects.

The underlined text identifies a principle which can be broadly applicable to almost everything we do. We make recommendations based upon information which ideally we share with our patients and they make decisions regarding whether they will adopt our recommendations. If physicians are rewarded for patients making particular decisions, it creates an incentive for physicians to frame decisions so they benefit. For example, the NQMC has a quality measure entitled:
Preventive care and screening: percentage of female patients who had a mammogram performed during the two-year measurement period.
The description of the measure is the following:
This measure is used to assess the percentage of female patients aged 50 to 69 years who had a mammogram performed during the two-year measurement period.
The math is straight forward:
Denominator Description
All female patients aged 50 to 69 years at the beginning of the two-year measurement period
Numerator Description
Female patients who had a mammogram performed
And there is an out for those who decline, although the documentation requirements are vague. My guess is it will be much easier hide the patient materials from the Annals and frame the discussion where everyone agrees to be screened.

There are a host of other measures relating to issues such as prostate cancer screening, hypertension control, anti-coagulation associated with atrial fibrillation, and colon cancer screening to name but a few.  In each of these contexts, physicians performance will be assessed by measuring what percentage of their patients were treated or screened. The interventions in question often are unlikely to directly benefit those to which they are applied and it is not unreasonable to predict that if the possible benefits are framed in such a way to convey that information, many patients would decline the interventions if they are fully briefed.

The data may show that much of what we push is essentially worthless but that may not matter. "Quality" metrics will reward physicians for promoting dubious interventions. There is no question in my mind that we can talk most patients into basically anything and we are most inclined to talk them into things that can be explained quickly and are financial winners. We are least inclined to spend time explaining nuanced concepts which undermine the economic basis for our practices. Few are inclined to spend time telling patients that the very tools heavily sold as saving lives may not be worthwhile. The people you explain this to may get cancer. Send  them for a mammogram and find a cancer you are a hero.  It appears the genie is out of the bottle and will not be put back in.

Saturday, April 7, 2012

Who needs the stinkin' constitution anyway when it gets in the way of things working the way I want them to work?

Here is yet another indication that state power is getting out of hand...

Another intersection of science, politics, and advocacy

When science's major patron is controlled in the political realm, it is not hard to predict when science and politics clash...

What are we coming to?

An interesting post...

Supreme Court Ground Hog Day

One of my favorite movies is the Bill Murray classic "Ground Hog Day" where he plays a reporter covering the activities on Punxsutawney Phil in Punxsutawney, Pennsylvania on Ground Hog Day. He finds himself waking up again and again on the same morning of February 2 (Ground Hog Day), forced to relive this day until he "gets it right". Ultimately, he succeeds in doing so but not before he has more than a few stumbles.

Like much of the US populace, I have been an earnest observer of the health care law debate and most recently, the landmark case which has just been argued in the US Supreme Court. I have taken this opportunity to pull out my Teaching Company courses on Civil Liberties and the Bill of Rights (Professor John E. Finn) and The History of the Supreme Court (Professor Peter Irons). They should be required ready (or listening) for all the talking heads and pundits who pretend to speak with authority on the subject.

My perspectives on the current controversy are the following. First, this is not a debate about health care.  I cannot help but see the debate on the current health care law as fitting in to a long standing debate on the role and extent of the Federal government power. For those who are convinced that we are dealing with settled law and the "right answer" is obvious, they are obviously ignorant of history and closed minded. Since the founding of the Republic, there have been tensions between state and Federal governments and between the various branches of the Federal government. Those tensions are an essential element of why our system which relies of division of power and checks and balances works as well as it does. Where some see conflict and gridlock, I see appropriate control of state power. It may serve as an impediment to getting certain things done, both constructive and destructive.

In listening to the Teaching Company course, I could not help but see parallels between the current controversy and Supreme Court cases which go back over one hundred years. In multiple Supreme Court cases which were extremely contentious at the time, the recurrent themes revolved around the role of the Court as a final arbiter of decisions made by state and federal legislatures to regulate commercial activities.

Late in the 19th century, the Supreme Court decided in the case of Munn v. Illinois where they upheld a state law setting maximum rates for grain storage by a Chicago company. This decision broke precedent from earlier Courts in that it upheld the power of state legislatures to regulate private contract and was denounced as being subversive of the rights of private property. While our current perspective may be that this was nothing unusual, we perhaps have lost perspective on how private property has historically been viewed as being essential to liberty. Ultimately, concepts revolving around private property and freedom of contract are central to the health care law debate.
"No other rights are safe where property is not safe." -- Daniel Webster 
The Munn case actually served as the impetus for the formation of the American Bar Association, whose original raison d'etre was to get the Munn decision reversed. This was ultimately accomplished shortly after the turn of the century with the famous (infamous) Lochner v. State of New York. In this case the State of New York passed a law limiting the hours of  bakers. This was challenged by a baker in Utica New York who claimed that the state law violated his 14th amendment rights, primarily what was interpreted as liberty to contract with others. Ultimately the Lochner decision became a rallying point for the progressive movement and the definition of inappropriate judicial activity among academic legal circles and has been linked to other decisions such as Plessy v. Ferguson.

However,  George Mason University law professor and legal scholar scholar David Bernstein (who actually has published peer reviewed material unlike other so-called legal scholars)  has recently written a book re-analyzing Lochner and providing evidence that it served as the foundation for limiting egregious state laws such as Jim Crow laws and xenophobic, anti-immigrant statutes. As noted by Damaon Root in his piece in Reason Magazine:

The true origins of the Bakeshop Act lie in an economic conflict between unionized New York bakers, who labored in large shops and lobbied relentlessly in favor of the law, and their nonunionized, mostly Jewish and Italian immigrant competitors, who tended to work longer hours in small, old-fashioned bakeries. “A ten-hour day would not only aid those unionized bakeries who had not successfully demanded that their hours be reduced,” Bernstein observes, “but would also drive out of business many old-fashioned bakeries that depended on flexible labor schedules.” The large corporate bakeries joined the union in supporting the Bakeshop Act. After all, it was in their economic interest to favor regulations that crippled the competition......
Drawing on both previous legal scholarship and his own extensive historical research, Bernstein offers a definitive account of this misunderstood and unjustly maligned case. Not only did Lochner represent the victory of small-scale producers over large, politically connected special interests, Bernstein points out, but the ruling led directly to several of the Supreme Court’s most important early decisions in favor of civil rights and civil liberties under the 14th Amendment, including Buchanan v. Warley, the landmark 1917 case in which the National Association for the Advancement of Colored People scored its first victory before the Supreme Court. If anyone consistently sided with the powerful against the powerless, it was Lochner’s Progressive Era critics. Progressive legal activists didn’t just take a dim view of individual rights under the Constitution. They typically supported state action in all of its vilest forms, including Jim Crow laws and anti-immigrant laws.....
In 1919 the state of Nebraska passed a law banning both public and private school teachers from instructing young children in a foreign language. As Bernstein explains, the ban was popular with more than just the local nativists. “Banning or heavily regulating private schools was also supported by many Progressives,” he notes, “who thought public schools essential in winning the citizenry’s loyalty to an increasingly activist state.”Thankfully the Supreme Court saw things differently. In a sweepingly libertarian opinion that relied on Lochner’s broad defense of individual rights, conservative Justice James C. McReynolds held that the 14th Amendment’s Due Process Clause secured the right of private school teacher Robert Meyer to earn a living by teaching in his native language of German. Furthermore, McReynolds wrote in the 1923 case Meyer v. Nebraska, liberty “denotes not merely freedom from bodily restraint but also the right of the individual to contract, to engage in any of the common occupations of life, to acquire useful knowledge, to marry, establish a home and bring up children,” and “to enjoy those privileges long recognized at common law as essential to the orderly pursuit of happiness by free men.” 

Many of the Lochner precedents were reversed in an aftermath of the New Deal and FDR's strong arming of the Court. Dr. Iron's discussed the events revolving around what was referred to as the "Four Horseman of Reaction", although I believe his handling of this discussion could have been more even handed. Whether FDR's actions actually swayed the Court or whether they had already changed their minds prior to the announcement of  his Court packing plan is debated to this day. With the transition to a Progressive agenda on the High Court, the central importance of private property and contract  waned, being replaced by more emphasis on other rights (speech, privacy). This trend has continued and the current health care law debate is a logical point given the history. The importance placed on legal protection of private property and contract has waned and the decision in front of the Court now is perfectly logical if one 's perspective is that this trend needs to continue. If one's perspective is that property and contract are essential pillars in the protection of liberty, then considerations other than protection of liberty are of secondary importance. The point is the major contention is not about health care per se.

Even now, the right and the left trade barbs, accusing justices of failing to follow long standing precedent and/or practicing judicial activism. What one side views as inviolable precedent is viewed by their opponents historical mistakes which cry out to be fixed. Where one side views Lochner as an example of the Court inserting personal opinion regarding property and economic justified no explicit written tenants within the Constitution, that same group has no problems with finding rights of privacy justified by Penumbras and emanations in Griswold vs Connecticut. In political battles principles and consistency are really not an asset. The ends justify the means. From the perspective of proponents of the mandate, they pose the question as to how are we to accomplish the Utopia of Universal Health care if we continue to be hamstrung with archaic limitations on state action based upon liberty rights, private property, and freedom of contract?

The parallels between the divided makeup of the Court now and in the mid-1930's is eery. I am actually surprised that  I have not heard any similar slogans portraying Justices Alito, Roberts, Thomas, and Scalia  as the new four horseman of reaction. If the health care mandate is found to be unconstitutional, I am sure that this will surface in the Presidential campaign. Mr. Obama will redoubtably stop channeling the Republican Lincoln and begin to channel the Democratic FDR. 

What does this all mean and how are we to interpret the current events within the context of these historical events? In my humble opinion what this means is that health care is not different. The overarching concerns which are relevant to health care law and the delivery of health care are ultimately governed by principles no different from the concerns which were relevant to Munn or Lochner or any number of other important Court decisions which impacted law and economic activity in general.  My view of the court is that is should be both very powerful and very limited. It is powerful in that it can over rule other branches of government on the basis of constitutionality. It is very limited in that it cannot initiate legislation and it actions are limited by the Supreme Law of the US; what is written in the US Constitution.  If the Congress can make a law which compels citizens to enter in contractual agreements in health care which they they do not want, it means that Congress can compel citizens to enter in any contractual agreement in any economic realm. I simply cannot see that this will be a good thing.

This is not about health care. It is about how much we limit state power, even if it potentially affects the ability of the Federal Government to take action to address individual difficult and complex problems which affect citizens of the US. If the Supreme Court becomes engulfed in micromanagement issues, the game is over.

  • We shall never prevent the abuse of power if we are not prepared to limit power in a way which occasionally may prevent its use for desirable purposes. Friedrich Hayek - The Road to Serfdom

No worry, however.  I am the eternal optimist. Like Bill Murray, we will wake to the sounds of "I got you babe", get out of bed, and do it over and over again until we get it right. It may take a while.

Monday, April 2, 2012

Very disturbing

Many activities are based upon trust. While medical research is not an activity that is commonly viewed as requiring trust, there is a faith and trust component.
During a decade as head of global cancer research at Amgen, C. Glenn Begley identified 53 "landmark" publications -- papers in top journals, from reputable labs -- for his team to reproduce. Begley sought to double-check the findings before trying to build on them for drug development.Result: 47 of the 53 could not be replicated. He described his findings in a commentary piece published on Wednesday in the journal Nature.
None of the non-reproducible studies identified. This represents a systems problem. It is non-rewarding at best and difficult to reproduce and publish what someone has already done. The incentives are to publish what appears to be novel and whether you are correct or not does not appear to be a particularly crucial aspect. I would be intrigued to whether there is any relationship between numbers of citations and the ability to replicate findings.