HealthLawProf Blog

Attempted Suicide Is Not a Crime--Unless You're Pregnant

I've written before about a murder prosecution in Indianapolis against a woman who swallowed rat poison in a suicide attempt while she was 33 weeks pregnant. If convicted, she would receive a minimum sentence of 45 years in prison, with the possibility of capital punishment. The trial court judge refused to dismiss the charges, and the court of appeals will consider the motion to dismiss next month. Nada Stotland and I wrote about the case in today's Indianapolis Star.

In about two weeks, I'll be filing an amicus brief on behalf of the American College of Obstetricians and Gynecologists, other medical groups, and individuals in support of the motion to dismiss charges. Many professors of medicine, bioethics and law have agreed to participate.  Others interested in doing so should contact me at dorentli@iupui.edu

[DO]

Auditing Studies of Anti-Depressants

Marcia Angell has kicked off another set of controversies for the pharmaceutical sector intwo recent review essays in the New York Review of Books. She favorably reviews meta-research that calls into question the effectiveness of many antidepressant drugs:

Kirsch and his colleagues used the Freedom of Information Act to obtain FDA reviews of all placebo-controlled clinical trials, whether positive or negative, submitted for the initial approval of the six most widely used antidepressant drugs approved between 1987 and 1999—Prozac, Paxil, Zoloft, Celexa, Serzone, and Effexor. . . .Altogether, there were forty-two trials of the six drugs. Most of them were negative. Overall, placebos were 82 percent as effective as the drugs, as measured by the Hamilton Depression Scale (HAM-D), a widely used score of symptoms of depression. The average difference between drug and placebo was only 1.8 points on the HAM-D, a difference that, while statistically significant, was clinically meaningless. The results were much the same for all six drugs: they were all equally unimpressive. Yet because the positive studies were extensively publicized, while the negative ones were hidden, the public and the medical profession came to believe that these drugs were highly effective antidepressants.

Angell discusses other research that indicates that placebos can often be nearly as effective as drugs for conditions like depression. Psychiatrist Peter Kramer, a long-time advocate of anti-depressant therapy, responded to her last Sunday. He admits that “placebo responses . . . have been steadily on the rise” in FDA data; “in some studies, 40 percent of subjects not receiving medication get better.” But he believes that is only because the studies focus on the mildly depressed:

The problem is so big that entrepreneurs have founded businesses promising to identify genuinely ill research subjects. The companies use video links to screen patients at central locations where (contrary to the practice at centers where trials are run) reviewers have no incentives for enrolling subjects. In early comparisons, off-site raters rejected about 40 percent of subjects who had been accepted locally — on the ground that those subjects did not have severe enough symptoms to qualify for treatment. If this result is typical, many subjects labeled mildly depressed in the F.D.A. data don’t have depression and might well respond to placebos as readily as to antidepressants.

Yves Smith finds Kramer’s response unconvincing:

The research is clear: the efficacy of antidepressants is (contrary to what [Kramer's] article suggests) lower than most drugs (70% is a typical efficacy rate; for antidepressants, it’s about 50%. The placebo rate is 20% to 30% for antidepressants). And since most antidepressants produce side effects, patients in trials can often guess successfully as to whether they are getting real drugs. If a placebo is chosen that produces a symptom, say dry mouth, the efficacy of antidepressants v. placebos is almost indistinguishable. The argument made in [Kramer's] article to try to deal with this inconvenient fact, that many of the people chosen for clinical trials really weren’t depressed (thus contending that the placebo effect was simply bad sampling) is utter[ly wrong]. You’d see the mildly/short-term depressed people getting both placebos and real drugs. You would therefore expect to see the efficacy rate of both the placebo and the real drug boosted by the inclusion of people who just happened to get better anyhow.

Felix Salmon also challenges Kramer’s logic:

[Kramer's view is that] lots of people were diagnosed with depression and put onto a trial of antidepressant drugs, even when they were perfectly healthy. Which sounds very much like the kind of thing that Angell is complaining about: the way in which, for instance, the number of children so disabled by mental disorders that they qualify for Supplemental Security Income (SSI) or Social Security Disability Insurance (SSDI) was 35 times higher in 2007 than it was in 1987. And it’s getting worse: the editors of DSM-V, to be published in 2013, have written that “in primary care settings, approximately 30 percent to 50 percent of patients have prominent mental health symptoms or identifiable mental disorders, which have significant adverse consequences if left untreated.”

Those who would defend psychopharmacology, then, seem to want to have their cake and eat it: on the one hand it seems that serious mental health disorders have reached pandemic proportions, but on the other hand we’re told that a lot of people diagnosed with those disorders never really had them in the first place.

That is a very challenging point for the industry to consider as it responds to concerns like Angell’s. The diagnosis of mental illness will always have ineradicably economic dimensions and politically contestable aims. But doctors and researchers should insulate professional expertise and the interpretation of maladies as much as possible from inappropriate pressures.

How can they maintain that kind of independent clinical judgment? I think one key is to assure that data from all trials is open to all researchers. Consider, for instance, these findings from a NEJM study on “selective publication:”

We obtained reviews from the Food and Drug Administration (FDA) for studies of 12 antidepressant agents involving 12,564 patients. . . . Among 74 FDA-registered studies, 31%, accounting for 3449 study participants, were not published. Whether and how the studies were published were associated with the study outcome. A total of 37 studies viewed by the FDA as having positive results were published; 1 study viewed as positive was not published. Studies viewed by the FDA as having negative or questionable results were, with 3 exceptions, either not published (22 studies) or published in a way that, in our opinion, conveyed a positive outcome (11 studies). According to the published literature, it appeared that 94% of the trials conducted were positive. By contrast, the FDA analysis showed that 51% were positive. Separate meta-analyses of the FDA and journal data sets showed that the increase in effect size ranged from 11 to 69% for individual drugs and was 32% overall. (emphasis added).

Melander, et al. also worried (in 2003) that, since “The degree of multiple publication, selective publication, and selective reporting differed between products,” “any attempt to recommend a specific selective serotonin reuptake inhibitor from the publicly available data only is likely to be based on biased evidence.” Without clearer “best practices” for data publication, clinical judgment may be impaired.

Full disclosure of study funding should also be mandatory and conspicuous, wherever results are published. Ernest R. House has reported that, “In a study of 370 ‘randomized’ drug trials, studies recommended the experimental drug as the ‘treatment of choice’ in 51% of trials sponsored by for-profit organizations compared to 16% sponsored by nonprofits.” The commodification of research has made it too easy to manipulate results, as Bartlett & Steele have argued:

One big factor in the shift of clinical trials to foreign countries is a loophole in F.D.A. regulations: if studies in the United States suggest that a drug has no benefit, trials from abroad can often be used in their stead to secure F.D.A. approval. There’s even a term for countries that have shown themselves to be especially amenable when drug companies need positive data fast: they’re called “rescue countries.” Rescue countries came to the aid of Ketek, the first of a new generation of widely heralded antibiotics to treat respiratory-tract infections. Ketek was developed in the 1990s by Aventis Pharmaceuticals, now Sanofi-Aventis. In 2004 . . . the F.D.A. certified Ketek as safe and effective. The F.D.A.’s decision was based heavily on the results of studies in Hungary, Morocco, Tunisia, and Turkey.

The approval came less than one month after a researcher in the United States was sentenced to 57 months in prison for falsifying her own Ketek data. . . . As the months ticked by, and the number of people taking the drug climbed steadily, the F.D.A. began to get reports of adverse reactions, including serious liver damage that sometimes led to death. . . . [C]ritics were especially concerned about an ongoing trial in which 4,000 infants and children, some as young as six months, were recruited in more than a dozen countries for an experiment to assess Ketek’s effectiveness in treating ear infections and tonsillitis. The trial had been sanctioned over the objections of the F.D.A.’s own reviewers. . . . In 2006, after inquiries from Congress, the F.D.A. asked Sanofi-Aventis to halt the trial. Less than a year later, one day before the start of a congressional hearing on the F.D.A.’s approval of the drug, the agency suddenly slapped a so-called black-box warning on the label of Ketek, restricting its use. (A black-box warning is the most serious step the F.D.A. can take short of removing a drug from the market.) By then the F.D.A. had received 93 reports of severe adverse reactions to Ketek, resulting in 12 deaths.

The great anti-depressant debate is part of a much larger “re-think” of the validity of data. Medical claims can spread virally without much evidence. According to a notable meta-researcher, “much of what medical researchers conclude in their studies is misleading, exaggerated, or flat-out wrong.” The “decline effect” dogs science generally. Statisticians are also debunking ballyhooed efforts to target cancer treatments.

Max Weber once said that “radical doubt is the father of knowledge.” Perhaps DSM-VI will include a diagnosis for such debilitating skepticism. But I think there’s much to be learned from an insistence that true science is open, inspectable, and replicable. Harvard’s program on “Digital Scholarship” and the Yale Roundtable on Data and Code Sharing* have taken up this cause, as has the work of Victoria Stodden.

We often hear that the academic sector has to become more “corporate” if it is to survive and thrive. At least when it comes to health data, the reverse is true: corporations must become much more open about the sources and limits of the studies they conduct. We can’t resolve the “great anti-depressant debate,” or prevent future questioning of pharma’s bona fides, without such commitments.

*In the spirit of full disclosure: I did participate in this roundtable.

The "July Effect" Confirmed

It has long been suspected that July is not a good time to seek medical care at a teaching hospital as new trainees join the care teams. Dr. John Young and colleagues writing in the Annals of Internal Medicine, here, demonstrate this is no myth. Such "cohort turnover" does indeed lead to the chillingly labelled "August killing season." Concentrating on what the researchers viewed to be high-quality studies they found considerable correlation between cohort turnover and increased mortality. A similar negative picture emerged with regard to increased hospital stays, hospital bills and other efficiency metrics. How do we fix this? The researchers suggest looking at workload burdens during the turnover and also staggering the way the cohorts move in and out of the system. So, there's another one to add to the process reform list. [NPT]

 

Guest Blogger Eleanor D. Kinney: Greetings from Puerto Vallarta!!

 El 10 de Julio

Greetings from Puerto Vallarta!! 

 

I am your guest blogger for July. I will be blogging from South of the Border – precisely from Puerto Vallarta, Jalisco, Mexico. My major topic in my guest blog will be health care in Mexico. There is much to learn from colleagues south of the border.

Mexico has a relatively advanced health care sector with morbidity and mortality patterns of modern industrialized countries. While there is still poverty in Mexico, with persistence of diarrheal and other infectious disease indicative of third world countries, there is greatly increasing morbidity and mortality from coronary artery disease, diabetes and other chronic diseases that plague more developed countries. See World Health Organization, Country Cooperation Strategy:  Mexico (2006). Indeed, Mexico is now experiencing a tremendous epidemic of diabetes. Elizabeth Barclay, In Mexico, Diabetes Strains Lives and Budgets, New York Times, June 12, 2007.   

Mexico's social security system provides direct health care services to about 50 percent of the population who work or have a family member who work in the formal economic sector. The Mexican Institute of Social Security (Instituto Mexicano de Seguro Social (IMSS)) covers approximately 80 percent of these private sector beneficiaries. The Institute of Security and Social Services for State Workers (Instituto de Seguridad y Servicios Sociales para los Trabajadores del Estado (ISSSTE)) covers government workers and accounts for 17 percent of the beneficiaries. There are separate systems that provide health coverage and care sponsored by the Secretariat of National Defense (Secretaría de Defensa Nacional), the Secretariat of the Navy (Secretaría de Marina), and Mexican Petroleum (Petróleos Mexicanos (Pemex)).   These programs are financed with contributions from employees, employers, and/or government. See Tim L. Merrill and Ramón Miró (ed.), Mexico: A Country Study. Washington: GPO for the Library of Congress (1996).  

In 2003, the Mexican Congress amended the Ley General de Salud to establish the System for the Social Protection in Health (SPSS) for the uninsured population who were not otherwise eligible for coverage under IMSS or ISSSTE. Ley General de Salud [The General Law of Health], as amended, art. 18, Diario Oficial de la Federación [D.O.], 7 de Febrero de 1984 (Mex). The reform includes the Seguro Popular (SP), which is a health insurance scheme financed jointly by the federal government and the states. SP will expand health care coverage to the entire population of Mexico by 2012, starting with the poorest families. Specifically, the reform includes five actions: (1) legislation establishing entitlement to coverage for eligible families; (2) creation of explicit benefits packages; (3) funds to state ministries of health in proportion, calculated on the basis of eligible families within the state; (4) division of federal resources flowing to states into separate funds for personal and non-personal health services; and, (5) creation of a fund to protect families against catastrophic health expenditures.

In 2009, Mexico had an uninvited opportunity to showcase its public health and health care delivery capabilities in the H1N1 flu pandemic of 2009. That spring, Mexico experienced outbreaks of influenza-like illness (ILI). On April 12, 2009, Mexico confirmed an outbreak of ILI occurred in La Gloria in the state of Veracruz and reported this outbreak to the World Health Organization (WHO). Later in April, outbreaks of severe pneumonia in Distrito Federal (Mexico City) and San Luis Potosi precipitated increased surveillance throughout the country. The high fatality rate of the novel influenza A (H1N1) infection among younger, previously healthy people was particularly disturbing.

The WHO announced that this outbreak of influenza A (H1N1) virus in Mexico and the United States marked the beginning of a worldwide pandemic. Mexico reacted quickly and aggressively in its surveillance and social distancing measures. The Mexican government cooperated immediately with international health organizations and neighboring countries to address the flu outbreak. By mid- April, the Mexican government issued a national epidemiologic alert to all influenza-monitoring units and hospitals asking that they test and report all cases of severe respiratory illness. On April 24, the government ordered that all schools and large public gatherings, such as soccer games in Mexico City and surrounding areas, be closed or suspended for about ten days. By May, Mexican authorities reported that the outbreak had likely peaked in late April. WHO publically acknowledged that Mexico had been cooperative and forthright in addressing the influenza A (H1N1) outbreak.  World Health Organization, “Influenza-Like Illness in the United States and Mexico,” April 24, 2009. Mexico’s decisive actions did much to mitigate the spread of the H1N1 flu pandemic throughout the world. 

In my next blog entry, I am going to talk more about Mexico’s efforts to extend universal coverage for all its citizens being with the poorest. The third blog entry will address portability of health insurance across the borders and will focus on making Medicare fully portable. The final blog entry will assess the impact of the North American Free Trade Agreement (NAFTA) on the Mexican health care sector.  

 I look forward to comments and discussion.  

 Hasta la Vista! 

-Guest Blogger Eleanor Kinney

  

Introducing Guest Blogger Eleanor D. Kinney

We are very pleased to welcome our Guest Blogger for July, Eleanor D. Kinney. Here is her bio:

Eleanor D. Kinney is the the Hall Render Professor of Law Emeritus and founding director of the William S. and Christine S. Hall Center for Law and Health at Indiana University School of Law – Indianapolis.  She is also an adjunct professor in the Schools of Medicine and Public and Environmental Affairs.  A widely published author and respected lecturer on the subjects of America’s health care system, medical malpractice, health coverage for the poor, and issues in administrative law, Professor Kinney is author or co-author of numerous law review articles, peer-reviewed health policy articles, book chapters and book reviews. She recently published Protecting American Health Care Consumers (Duke University Press 2002) and edited the Guide to Medicare Coverage Decision-Making and Appeals (ABA Publishing 2002).

Professor Kinney received her J.D. and B.A. (with distinction in history) from Duke University.  She also has a masters degree in public health from the University of North Carolina – Chapel Hill and a masters degree in European history from the University of Chicago.  After graduating from law school, she practiced law for four years at Squire, Sanders & Dempsey in Cleveland, Ohio and then worked as an estate planning officer for Duke University Medical Center. After earning her master’s degree in public health, she served as program analyst for the U.S. Department of Health and Human Services in Washington, D.C.  She received an award from the DHHS Office for Civil Rights for Distinguished Performance on the New York City Health and Hospitals Corporation Investigation for 1979‑1980.  Before joining the IU faculty in 1984, she was Assistant General Counsel of the American Hospital Association.

Professor Kinney has served as a consultant to the Administrative Conference of the United States, President Clinton’s Task Force for Health Care Reform, and the Indiana Commission on Health Care for the Working Poor. She has been appointed by the governor of Indiana to the Executive Board of the Indiana State Department of Health and to other task forces and advisory boards.  During 1999-2000, Professor Kinney was a Fulbright Fellow at the National University of La Plata in La Plata, Argentina.  In 2005-2006, Professor Kinney served as Chair of the American Bar Association's Section on Administrative Law and Regulatory Practice and was inducted as a fellow of the Section in 2007. 

In 2010, she received the Jay Healey Award for Excellence in Teaching, Health Law Professor’s Section of the American Society for Law, Medicine and Ethics. In 2022, she received the IUPUI Senior Woman’s Leadership Award. In 2000, she received Distinguished Alumna Award for Lifetime Achievement from her alma mater, Emma Willard School. In 1986, she was awarded the Best New Professor Award by the Student Bar Association of Indiana University School of Law – Indianapolis.  Professor Kinney is a member of the American Law Institute. 

Professor Kinney’s current research interests focus on the realization of the international human right to health, free trade policy and health care, improved administrative law and procedures for a reformed health law system and an improved system for the resolution of medical malpractice claims.

Your Health Insurance Exchanges Primer

A few months ago predicting the actual date for the announcement of the ACO proposed rule, here, was (almost) as exciting as awaiting a new product announcement from Apple. Well, just as Apple spoiled "Christmas" the other month by pre-announcing the contents of a Steve Jobs product presentation, so Secretary Sibelius, here, has told us that the Exchanges rule is being published today with a summary that somewhat desperately tries to make them appear more user-friendly than the frankly geeky mechanisms they truly are. There are some good resources for the Exchanges newbie, including Julie Appleby's March primer in the Washington Post, here and Sarah Kliff writing for Politico, here. For more detail I recommend Jon Kingsdale and John Bertko writing in Health Affairs, here and, of course, the masterful Tim Jost writing for the Commonwealth Fund, here. Update, HHS site now has Exchanges overview plus links to NPRMs, here. [NPT]