Professor O. Carter Snead on Bioethics and Responsible Discussion

“Embryos are living members of the human species,” declared Professor O. Carter Snead of Notre Dame Law School during a presentation to Professor Jordan Paradise’s Law and Genetics class at Seton Hall Law School. Professor Snead, former General Counsel to The President’s Council on Bioethics under President George W. Bush, lectured and met with students  during his residence as Visiting Health Law Scholar  at Seton Hall Law School. Professor Snead presented a lecture to the Law and Genetics class that compared embryonic stem cell patenting in the United States and Europe.

In an interview with Health Reform Watch before his presentation, Professor Snead reflected on his career in bioethics, the role bioethics plays in politics, and the current need for bioethical input.

Regarding what informs his beliefs as a lawyer practicing in bioethics, Professor Snead said before serving as General Council member he “didn’t have settled opinions” and decided his opinions by “listening to debates” and following the teachings of bioethicists such as Michael Sandel, Robert George, Leon Kass, and George Annas. However, he noted that he has always had one main concern: self-governance.  As such, he disapproves of an “enclave of elite thinkers telling everybody what to do and think.”  In order to better democratize bioethical issues, Professor Snead emphasized the importance of recognizing “We all have standing to debate and discuss.  There’s no special expertise necessary to reflect on normative questions.”

In promoting the need for debate on bioethical issues, Professor Snead used physician-assisted suicide as an example to explain the shortfallings of a purely normative approach.  In setting-up a situation where physician-assisted suicide may seem reasonable to many, or “in a vacuum” as Professor Snead referred to it, moral dispute may be limited.  However, he stressed looking at the issue and its “collateral” effects— including “exploitation of the poor, abuse of the disabled, and fraud and abuse.” Professor Snead contended that in order to avoid the collateral consequences, “We have to sacrifice [the] liberty of the small sliver of people who might be able to autonomously choose to end their own lives free from coercion, fraud, and abuse.” Which is to say that those most vulnerable— the poor, the disabled and those most readily susceptible to fraud and abuse—are not necessarily best situated to advocate for themselves. If these most vulnerable are to be properly considered, “the vacuum,” and those who construct it, must be left behind and the actuality—in its broader sense—considered.

This example led Professor Snead to advocate for responsible discussion on bioethical issues and criticism for politicians who inappropriately use the issue on their campaign platform.  ”Politicians I.D. wedge issues and try to spin the issues.  We end-up with a dishonest discussion,” stated Professor Snead.

In answering a question on what role American bioethical principles play in the global community, Professor Snead said he disfavors “exporting our bioethical approach,” noting that bioethics and moral anthropology closely coincide.  He stated, “Who you think human beings are, what are our relations to each other” is what informs a nation’s bioethical beliefs and that there is “no formulaic way.” However, Professor Snead did note, “Bioethics is an application of deeper human principles across a variety of factual and cultural contexts.”  As a law professor, he uses this philosophy and teaches “by exposing students to competing views in a neutral fashion, exploring the strengths and weaknesses of the various approaches.”

On the topic he presented to the Law and Genetics class, Professor Snead’s bioethical standpoint is that embryos are human subjects entitled to “A baseline of inalienable rights,” and further noted that, “Embryonic stem cells are not yet capable of producing therapies.”  He pointed to the potential therapeutic value of induced pluripotent stem (iPS) cells, a type of adult stem cell, and described the cells: “easier to work with, less ethically contentious, and seems to be doing the same as embryos.”  Addressing concerns of other nations conducting research with embryonic stem cells, Professor Snead stated: “The best researchers are in the US.  I’m not worried about falling behind in any area of scientific inquiry.”

Project Shows Substantial Decrease in Colorectal Surgery Infections

There was a time in medical science when doctors did not wash their hands prior to operating on their patients (some might say, that to a greater extent than seems possible, this is still the case among medical professionals and point to a number of recent studies as uncomfortable proof). This failure of doctors to wash hands in the medical forum led to the otherwise avoidable death of many of their patients. Up until the mid 1800s, medical science had simply not made the connection between bacteria, transference, infection and death.

Ignaz Semmelweis, a Hungarian physician who was Director of the maternity clinic at the Vienna General Hospital in Austria, made the connection after what is said to have been an extensive statistical analysis in the 1840s, and demonstrated that hand-washing could drastically reduce the number of women dying during childbirth. He introduced a rigorous hand scrubbing protocol and enough women stopped dying to earn him the honorific, “savior of our mothers.”

But as an article from the UK’s Science Museum, Exploring the History of Medicine, points out

Until the late 1800s surgeons did not scrub up before surgery or even wash their hands between patients, causing infections to be transferred from one patient to another. Doctors and medical students routinely moved from dissecting corpses to examining new mothers without first washing their hands, causing death by puerperal or ‘childbed’ fever as a consequence. As dissection became more important to medical practice in the 1800s, this only increased.

Semmelweis showing again that the common sense of one era is the uncommon brilliance of one bygone.

Which brings us to this latest study/project showing new solutions which decrease the risk of colorectal surgical site infection. According to the Associated Press in an article about the project,

“Almost 2 million health care-related infections occur each year nationwide; more than 90,000 of these are fatal.”

And:

“Infections linked with colorectal surgery are particularly common because intestinal tract bacteria are so abundant.”

 

According to the press release regarding the Project,

A project to reduce colorectal surgical site infections (SSIs) saved more than $3.7 million in costs for 135 avoided SSIs. The two-and-a-half year project included seven hospitals and was directed by the Joint Commission Center for Transforming Healthcare in collaboration with the American College of Surgeons.

The participating hospitals were able to reduce superficial incisional SSIs, which affect skin and underlying tissue, by 45 percent and all types of colorectal SSIs by 32 percent. The average length of stay for hospital patients with any type of colorectal SSI decreased from an average of 15 days to 13 days. In comparison, patients with no SSIs had an average length of stay of eight days.

The press release further notes that

Colorectal surgery was identified as the focus of the project because SSIs are disproportionately higher among patients following colorectal surgeries. Colorectal surgery is a common procedure across different types of hospitals, can have significant complications, presents significant opportunities for improvement, and has high variability in performance across hospitals. The project addressed preadmission, preoperative, intraoperative, postoperative and post discharge follow-up processes for all surgical patients undergoing emergency and elective colorectal surgery, with the exception of trauma and transplant patients and patients under the age of 18. Project participants studied the potential factors that contribute to all three types of colorectal SSIs – superficial incisional, deep incisional and organ space SSIs, which affect organs and the space surrounding them.

 

The AP article:

Solutions included having patients shower with special germ-fighting soap before surgery, and having surgery teams change gowns, gloves and instruments during operations to prevent spreading germs picked up during the procedures.

Some hospitals used special wound-protecting devices on surgery openings to keep intestine germs from reaching the skin.

The average rate of infections linked with colorectal operations at the seven hospitals dropped from about 16% of patients during a 10-month phase when hospitals started adopting changes to almost 11% once all the changes had been made.

The AP article further notes the timely nature of the Project’s benefits:

Besides wanting to keep patients healthy, hospitals have a monetary incentive to prevent these infections. Medicare cuts payments to hospitals that have lots of certain health care-related infections, and those cuts are expected to increase under the new health care law.

Stillbirth: An Interdisciplinary Approach to ‘Closing the Knowledge and Solution Gaps’*

In an article out in the American Journal of Obstetrics and Gynecology, the Global Alliance to Prevent Prematurity and Stillbirth (GAPPS)—a Gates Foundation-funded initiative of Seattle Children’s Hospital and the University of Washington School of Medicine’s Departments of Global Health and of Obstetrics and Gynecology—reports on its efforts to develop “a research agenda related to pregnancy, childbirth, and early life[.]”  In addition to interviewing scientific thought leaders and convening a “technical team of 13 prominent researchers from multiple disciplines in the developed and developing world,” the GAPPS spoke to “18 representatives of funding organizations—including government agencies, global foundations, and other financial partners—to gain a deeper understanding of the current perspectives, attitudes, and commitments of funders toward research on pregnancy, childbirth, and early life.”

The GAPPS’ conversations with funders surfaced a number of challenges to increasing funding, including 1) “a range of understanding of the issues[,]” 2) “varying degrees of interest in the topic[,]” and 3) concern about “the challenges of progress with such a long-term and complex problem.”  The authors, to their credit, do not deny that the question (questions, really) of what causes prematurity, stillbirth, and other pregnancy and early life problems are among the “most difficult … in biomedical research today.”  The authors note that “[d]ifferent biological pathways are involved in the adverse outcomes of pregnancy, and these can be characterized at different biological levels from the genome to the exposome (the combined effects of environmental influences).”

At the level of the exposome, recently-published research by investigators from New Jersey’s own UMDNJ-Robert Wood Johnson Medical School, brings us incrementally closer to understanding the effects of ambient air pollution on stillbirth, while exemplifying the complexity of the science involved.  Ambarina Faiz and colleagues compiled data contained in “New Jersey electronic birth certificate records for live births and fetal death certificates for stillbirths linked to their corresponding hospital delivery discharge records from 1998 to 2004[,]” along with data on air pollutants from 25 New Jersey Department of Environmental Protection monitoring stations.  Their analysis of the data revealed that “[i]ncreased concentrations of ambient air pollutants during pregnancy were associated with increased relative odds of stillbirth after adjustment for known risk factors for stillbirth, mean temperature, and a neighborhood level measure of socioeconomic status.”  Numerous questions remain, though.  The authors call for “molecular studies with specific biomarkers … to define more clearly the roles of specific pollutants and to investigate possible biologic mechanisms that lead to stillbirth.”

Drawing on what it learned from funders, as well as from scientific thought leaders and from the technical team it convened, the GAPPS developed eight recommendations aimed at encouraging such research, with the ultimate goal of “making every pregnancy a healthy pregnancy[.]”  The GAPPS calls for 1) determining and publicizing the true cost of prematurity, stillbirth, and other pregnancy and early life problems, 2) establishing alliances among funders, researchers, and other stakeholders, 3) agreeing on research priorities, and 4) promoting research opportunities, particularly opportunities for “new investigators from multiple disciplines.”  While these are clearly daunting tasks, the authors report that “[s]everal interviewees observed that the Bill and Melinda Gates Foundation has an unparalleled ability to persuade, convene, and organize important players, both nationally and internationally.  In particular, they pointed to the potential for the foundation to move the concept of coordinated funding forward.”  The prospect of a new clarity about research priorities, combined with a coordinated approach to funding, is a hopeful one for all of us since “healthy outcomes in pregnancy benefit everyone, directly and indirectly.”

*I thank Catherine Finizio, the Administrator of Seton Hall Law’s Center for Health & Pharmaceutical Law & Policy, for keeping me focused on this important issue.  (My prior posts are here, here, and here).  Cathy’s grandson, Colin Joseph Mahoney, was stillborn at 39 weeks gestation on November 10, 2008.

The Treatment of Neonates in Pending Legislation Permanently Reauthorizing the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act

Last week, the United States Senate took up debate of The Food and Drug Innovation and Safety Act, S 3187.  A similar bill, HR 5651, was voted out of the House Energy and Commerce committee earlier this month. In addition to re-authorizing user fees for drug and devices and newly authorizing user fees for biologics and generic drugs, the bills include provisions reauthorizing and making permanent both the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA). As reported here, S 3187 and HR 5651 are expected to pass the House and Senate in the coming weeks and to go to a conference committee in June. Lawmakers hope to present the final version of the legislation to President Obama before the Fourth of July.

The BPCA and the PREA are often described as taking a carrot and stick approach.  The BPCA is the “carrot,” providing a drug’s manufacturer with six additional months of protection from generic competition in return for studying the drug in children.  The PREA is the “stick,” requiring, as I explained here, “that, as a condition of FDA approval of a new drug application or supplemental drug application for a new active ingredient, new indication, new dosage form, new dosing regimen, or new route of administration, drugs be studied in children. Applicants must submit a ‘pediatric assessment’ which evaluates the drug’s safety and effectiveness for use in children and ‘supports dosing and administration’ for any pediatric sub-populations for which the drug is found to be safe and effective.  The PREA also requires applicants to request approval of the formulations appropriate for those sub-populations for which the drug is found to be safe and effective.”

While not without their flaws, the BPCA and the PREA have increased our knowledge of the safety and effectiveness of drugs when used in children.  As Daniel Frattarelli of the American Academy of Pediatrics testified before Congress earlier this year, as a “direct result of BPCA and PREA[,]” “we have gone from a situation where about eighty percent of time, the drugs we were using in children did not have FDA-approved pediatric labeling to today where that number is down to about fifty percent.”

In addition to reauthorizing permanently the BPCA and PREA, both S 3187 and HR 5651 make minor changes to the laws, addressing some but not all of the concerns raised in the Institute of Medicine’s February 2012 report, Safe and Effective Medicines for Children: Pediatric Studies Conducted under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. For example, the IOM suggested that “[m]ore timely planning, initiation, and completion of pediatric studies would benefit children[,]” and both bills require that companies submit the pediatric research plans required under PREA earlier in the process than they currently do.  The bills also include provisions designed to, in the words of one of the sponsors of HR 5651, “increase[] transparency on the status of pediatric clinical trials required under PREA” and to provide FDA the necessary enforcement tools to ensure that trials are completed on time.

One problem that the IOM discussed in its report that is only partially addressed in the draft legislation is the need for more studies of drugs in neonates, that is, infants up to four weeks old.  Per the IOM, “[f]rom 1998 through 2010, only 23 of the more than 350 labeling changes resulting from [studies conducted pursuant to the BPCA and the PREA] included information from studies with neonates.”  There were also “five products [that] had been studied in neonates and companies had received exclusivity, but no information from the neonatal studies was added to the labeling.”

The draft legislation incorporates the following provisions relating to neonates:

• Both the House and the Senate bills provide that if the FDA issues a request pursuant to the BPCA and “does not request studies in neonates, such request shall include a statement describing the rationale for not requesting studies in neonates.”

• Both the House and the Senate bills require that the reports that the FDA will be required to make to Congress every five years include a discussion of “the efforts made by the Secretary to increase the number of studies conducted in the neonatal population (including efforts made to encourage the conduct of appropriate studies in neonates by companies with products that have sufficient safety and other information to make the conduct of the studies ethical and safe)[.]“

• The House bill includes a provision that would ensure that the Pediatric Review Committee (PeRC), which is responsible for carrying out the BPCA and PREA, has as a member an agency employee with expertise in neonatology.

• The House bill also includes a provision requiring that the staff of the Office of Pediatric Therapeutics, which is “responsible for coordination and facilitation of all activities of the Food and Drug Administration that may have any effect on a pediatric population or the practice of pediatrics or may in any other way involve pediatric issues, including increasing pediatric access to medical devices[,]” 21 U.S.C. § 393a, include “one or more additional individuals with expertise in neonatology[.]“

Ensuring that individuals with expertise in neonatology serve on the Pediatric Review Committee and staff the Office of Pediatric Therapeutics will not guarantee that studies in neonates are conducted where appropriate.  The IOM concluded in its report that it did not have enough information to know whether additional expertise would have made a difference in the quality of the FDA’s review of studies in neonates.  It also wrote, however, that it “had some concerns about whether sufficient expertise in neonatology and neonatal pharmacology was brought to bear on some requests, for example, those for bacterial conjunctivitis and GERD.”   Common sense suggests that expertise in neonatology is a necessary but not sufficient condition for high quality review; the bill that comes out of conference committee should incorporate the two provisions from the House bill.

As the IOM emphasizes, industry-funded research conducted pursuant to the BPCA and the PREA will never be enough to build an adequate evidence base for drug treatment of neonates, because the BPCA and the PREA only apply to relatively new drugs.  This has a disproportionate effect, because, as the IOM explains, “[m]any drugs commonly used with premature and sick neonates are older drugs that have not been adequately evaluated in studies with this vulnerable age group.”  The IOM discusses an ongoing study of caffeine citrate, which is used to treat apnea of prematurity, which is following children treated with the drug through the age of twelve.  As the IOM notes, “[t]he study, which was funded by the Canadian Institute for Health Research, illustrates the importance of long-term studies of the benefits and risks of neonatal therapies and the importance of public funding for such studies, particularly for long-marketed drugs.”

An Uncertain Future for ICD-10

On February 14, 2012, Marilyn Tavenner, the acting Administrator of CMS, told reporters that CMS will “re-examine the timeframe” of the planned conversion to the ICD-10 code standard.  Presently, covered entities under HIPAA must fully convert from the ICD-9 coding system to ICD-10 by October 1, 2013.

ICD-10, which stands for the International Classification of Diseases, 10^th Revision, is a coding system that providers use for billing purposes and medical researchers also use for statistical analysis.  ICD-10 consists of 68,000 codes that will expand upon the 13,000 codes currently being used with ICD-9. The codes, each representing a separate medical service or diagnosis, are used by providers and hospitals when they submit their bills to the insurer. The providers receive payment for their services based upon the codes and the terms of their reimbursement agreement. From these codes, medical researchers are able to evaluate kind and frequency of care; with more than five times as many descriptive codes in the new system, many researchers and evidence based medicine proponents are said to look forward to the far greater depth of analysis the new coding system will offer. The United States already lags behind many countries in ICD-10 implementation and it is said that this compliance extension will widen the gap even further.

Two days after Ms. Tavenner’s announcement, HHS issued a news release stating that “HHS will initiate a process to postpone the date by which certain health care entities have to comply with ICD-10.” Kathleen G.  Sebelius, the Secretary of HHS, states in the news release that “we have heard from many in the provider community who have concerns about the administrative burdens they face in the years ahead. We are committing to work with the provider community to reexamine the pace at which HHS and the nation implement these important improvements to our health care system.”

HHS’s news release leaves a lot of questions unanswered. There is no hint at which “certain health care entities” will be granted an extension for compliance and how far off the new deadline will be. HHS claims they will “initiate a process,” which leads many to believe a formal rule making process with public comments will occur. This process could possibly take years to complete, which undoubtedly has caused a giant sigh of relief for providers and institutions across the country that feel ill-prepared for the 2013 deadline. Analysts at Health Care IT News estimate that the deadline could be pushed off a year or two if there is a formal rule-making process.

As the news of Ms. Tavenner’s announcement spread, members of the industry sent out messages cautioning that a complete overhaul of the current plan is unlikely.  Ms. Tavenner’s announcement, which happened at the American Medical Association (AMA) Advocacy Conference in Washington, D.C., was fittingly met with applause by AMA members. The AMA has publicly and vehemently opposed the current October 1, 2013 deadline.  In a January 17, 2012 letter addressed to Speaker of the House John A. Boehner, the Executive Vice President and CEO of the AMA James L. Madara M.D. pleaded with Speaker Boehner to stop the implementation of ICD-10. In the letter, Dr. Madara argues that the conversion “will create significant burdens on the practice of medicine with no direct benefit to individual patient care, and will compete with other costly transitions associated with quality and health IT reporting programs.” Of course, Dr. Madara is referring to the task of implementing an electronic health records (EHR) system in accordance with CMS’s meaningful use criteria, which entitles a covered entity to receive incentive payments from CMS. Dr. Madara also cites to what he deems to be the competing tasks of dealing with financial penalties for non-participation in Medicare programs, including e-prescribing and the Physician Quality Reporting System.

ICD-10 opponents also cite to the industry’s recent failure to comply with the January 1, 2012 deadline to comply with the transition to Version 5010, a HIPAA electronic transactions upgrade that is necessary to support ICD-10, as evidence that the industry is not ready for the ICD-10 change. In November 2011, CMS gave in to industry pressures to extend the 5010 compliance deadline an additional ninety days. It is undeniable that providers are already subject to tremendous demands under HIPAA and the HITECH Act, on top of Medicare cuts, which are placing significant financial stress and compliance burdens on the industry. It is not surprising that ICD-10 has met a lot of resistance from providers. However, it is no secret that providers and institutions are consistently successful lobbyists for their concerns and beliefs and it remains to be seen how CMS will proceed with the scheduled ICD-10 implementation and what compromises will be made.

Proponents of the ICD-10 system argue that the new coding system will create significant positive changes in the industry because it will help collect important data that will improve the quality of patient care, decrease costs, and collect statistics for medical research.  CMS and the Center for Disease Control and Prevention believe that the new codes will create more accurate and exact descriptions of diagnoses and inpatient procedures, which will improve efforts to track care, detect emerging health issues and improve quality. A report from Deloitte, a consulting firm, reported that the increased size and scope of the ICD-10 codes is expected to provide potential benefits in cost and quality measurement, public health, research, and organizational monitoring and performance measurement.  Whether a provider supports the change or not, Deloitte echoes the sentiment of many that advance planning is essential. Providers and institutions that have already invested time and money into the ICD-10 implementation are frustrated and upset by CMS’s decision to “reexamine” the current compliance deadline.  After all, no provider wants to see its large investment in the ICD-10 system put to waste.

The fact is that no one, perhaps even CMS and HHS, is certain about the date of the future ICD-10 implementation plan so perhaps the smartest choice for providers is to proceed with steps to continue the ICD-10 implementation. Considering the prospect of the financial disincentives attached with non-compliance, it seems like a risky choice for any provider to sit around and wait and see what may happen, especially when the ICD-10 implementation cannot happen overnight.  There are providers that started the ICD-10 conversion process back in 2009 when it was first introduced and they still have not completed the task. Unfortunately for providers, the ICD-10 conversion requires time, manpower, training, testing with payers, and significant technological changes that will carry high administrative and financial costs.  The Medical Group Management Association (MGMA), which opposes the ICD-10 implementation, estimates that it will cost a ten doctor practice more than $285,000 to convert to ICD-10, with software upgrades accounting for only $15,000 of that amount. According to the MGMA, the bulk amount would be for increases in claims queries, reductions in cash flow, and increased documentation time.  What it comes down to is that if a provider wants to be paid for its services, noncompliance with ICD-10 is not an option. The risk for successful claims processing and receiving payments in a timely fashion is present, but adequate preparation and testing well before the compliance deadline is the best way to combat this significant risk.

One thing is certain – until HHS releases a new rule and schedule for ICD-10 implementation, opponents will continue to argue that the costs to adopt the new system are too high, the task too onerous, and the rewards too speculative to justify such an undertaking.  Unless the industry comes together to find a solution for an easy transition, this could be a bumpy road until the ICD-10 transition is complete.

(Slow) Progress Towards Uncovering Sex-Linked Differences in Drug and Device Safety and Efficacy

In 2000, the General Accounting Office (since re-named the Government Accountability Office) reported that more women than ever were being included in clinical trials funded by the National Institutes of Health.  In fact, the GAO noted, over 50% of the participants in the trials that NIH funded in fiscal year 1997 were women.  At the same time, the NIH had made much less progress implementing the requirement that certain clinical trials it funds be designed to reveal sex-linked differences in a treatment’s safety and efficacy.  In 2012, sex-linked differences in responses to treatments are still not being studied in research funded by the government or by the private sector.  In a summary released last month of an Institute of Medicine workshop on the problem, Theresa Wizemann reports that “[e]ven when women are included in clinical trials, the results are often not analyzed by sex” despite “growing acknowledgement that men and women have substantial and widespread biologic differences.”

As its title — “Sex-Specific Reporting of Scientific Research” — suggests, a focus of the IOM Workshop was whether medical journals could drive reform in this area by requiring that authors report sex-specific data.  Wizemann writes that because “[r]esearchers are eager to have their papers published in high-profile journals[,]” “editorial policies implemented by those journals can be effective in modifying behavior.”  But several participants in the IOM Workshop noted that studying population subgroups poses “methodologic and analytic” challenges.  In many cases, Wizemann reports, “achieving statistical significance for subgroup analyses would require unattainable or unjustifiable numbers of participants.”  Workshop participant Gregory Curfman, who is the Executive Editor of the New England Journal of Medicine, “cautioned against editorial policies that require trials to be designed to reach valid statistical conclusions for males and females separately[,]” because “[s]uch editorial policies would create a ‘steep mountain to climb for investigators and for funding agencies[.]‘”

The participants in the Workshop seemed to be largely in agreement that journals could not, acting alone, re-shape “research culture to embrace consideration of sex differences as part of sound study design.”  There are steps that journals could (and should, I think) take short of dictating study design, though, including requiring study authors to tabulate and make available raw sex-specific data to facilitate future studies that draw on data from multiple trials.

Government agencies and other funders have a role to play too.  The NIH should more stringently enforce the statutory requirement that certain later-stage trials it funds be designed to evaluate sex-linked differences, and the FDA should take similar action with regard to trials funded by drug and device companies.

A study published last year by Sanket Dhruva, Lisa Bero, and Rita Redberg in the journal Circulation highlighted how little progress the FDA made on the device side over the last decade.  In 1994, the FDA issued a directive requiring that every time it makes a decision on an application for approval to market a new device, it issue a Summary of Safety and Effectiveness Data (SSED) that includes, among other things, a “gender bias” statement addressing the following two questions: (1) Did the proportion of men and women in the clinical trial reflect the distribution of the disease? and (2) Were there any sex-linked differences in safety or effectiveness?  Dhruva and colleagues reviewed all of the of the SSEDs for all of the cardiovascular premarket approval applications submitted and approved between 2000 to 2007 and found (1) that women were underrepresented in the underlying clinical trials and (2) that less than half (41%) of the SSEDs included the required “gender bias comment or analysis.”  Nearly a third (28%) did not even report the percentages of men and women enrolled in the studies supporting the application.  And, there was no improvement over time; “[t]here was no change in the presence of gender bias comments or analyses over the 8-year period” studied.

The FDA has been working for several years to address the problem and in December of 2011 it released a draft guidance in which it “strongly recommends” that device companies work closely with the agency to “investigate and report differences in study outcomes of treatment by sex.”

The Guidance provides clear direction for companies regarding (1) increasing the percentage of enrollees in device trials who are women, (2) designing studies to allow for the “consideration of sex and associated covariates” such as body size, (3) analyzing study data for sex-linked differences, and (4) “reporting sex-specific information in summaries and labeling for approved devices.”  Whether these strong recommendations translate into strong and consistent agency action remains to be seen, but the Guidance is an excellent start.  As Carolyn Clancy, the Director of the Agency for Healthcare Research and Quality, who participated in the IOM Workshop, emphasized, “[b]etter data on women would be better data for everyone,” allowing for more specific clinical practice guidelines and better-tailored care of individual patients.

Reorganization of UMDNJ to be Implemented this Year

On January 25, 2012, after nearly a decade of deliberations and strategic planning, the University of Medicine and Dentistry of New Jersey Advisory Committee issued its Final Report pursuant to a directive from Governor Chris Christie. The Report calls for and explains a proposed reorganization and “complete overhaul” of the University of Medicine and Dentistry, which will most likely be known as the New Jersey Health Sciences University once the Committee’s recommended changes commence. The implementation of these changes are said to be of a high priority for the Christie  administration. UMDNJ is one of the largest public entities in the state, operating at an annual budget of $1.7 billion.

The Committee made the following recommendations, which have been endorsed by Governor  Christie:

• A revamped and recast health sciences university based in Newark, which they suggest be named the New Jersey Health Sciences University (NJHSU). This powerful academic institution, with significantly increased autonomy for three units — University Behavioral Health Care, the School of Osteopathic Medicine and the Public Health Research Institute — will establish the foundation for a new era of medical education and patient care in our State.

• An affirmative and strong endorsement of support for the critical mission and role of University Hospital for the Newark community and for the State. The Committee recognized the hospital’s vital role while also noting that its precarious fiscal position must be addressed. To that end they are recommending a public/private partnership that would provide for the improved operations and long-term sustainability of University Hospital.

• A broader, expanded research university in southern New Jersey comprised of the assets of Rowan University and Rutgers University in Camden and encompassing, as well, the Cooper Medical School of Rowan University.

• Reaffirms Committee’s interim recommendation for institutional realignment of UMDNJ’s Robert Wood Johnson Medical School, the School of Public Health and the Cancer Institute of New Jersey into Rutgers University.

The Report stresses the urgency of the action proposed, emphasizing, “The time is now.”

Medical education and health care delivery are– particularly as they relate to UMDNJ– enormously complicated, but not so complicated that decisive action on behalf of the State and for the State’s benefit should be put off any longer.

Pointedly, as U.S. attorney, Chris Christie “led a two-year federal takeover of the institution in 2005, after Medicaid fraud was discovered.” Governor Christie is reported as saying that mismanagement and the magnitude of  UMDNJ problems that have accumulated over the years have led him to believe that the structure and scope of UMDNJ, as is, can no longer be managed effectively.   As such, under the proposed plan the university will be broken down into component parts. Thinking that time is of the essence, Governor Christie has announced that the reorganization will take place this year.

Governor Christie has said that he recognizes that the University Hospital is indispensable to the well being of the people within the region. The Report proposes to place the management of the hospital under a long-term public-private partnership, with the hope that this will “[enable] continued high quality medical programs, increase efficiency in operations and investment in capital improvements in the future.”

Some Newark residents, however, are said to oppose the plan, citing fears that privatization and the splitting off of UMDNJ units will take away jobs and resources. In contrast, Governor Christie is said to believe that the initiatives will aid the state’s efforts to attract health care and biomedical companies, and avail the University of more funding opportunities. Further rationales for the Commission’s recommendations include the ability to quickly implement the institution’s research at the medical school to benefit patients and that the changes will add substantially to the infrastructure for pharmaceutical and biomedical research.

Newark Mayor Cory Booker, who is still reviewing the reorganization report, stated that he “welcome[s] sensible reform but I would stand shoulder to shoulder with other leaders to ensure our residents don’t suffer a decline in the quality and scope of available healthcare and that we maintain abundant medical education opportunities in North Jersey.”

Research, the Avian Flu and Bioterrorism

In their zeal to keep us all alive, it seems fair to say that public health officials love bioterrorism preparedness measures. In fact, the only thing they might love planning for more is pandemics. So last month, when researchers at two different facilities revealed they were able to mutate the virulent H5N1 avian flu strain to pass between mammals simply through the air, the NIH was highly concerned.

The discovery is alarming because avian flu is considered one of the world’s deadliest pathogens, with a 60% mortality rate. But while avian flu viruses have infected humans in the past, those infections have come directly from birds. If the virus can be mutated into an airborne pathogen, the consequences can be catastrophic.

Two research teams (one led by Ron Fouchier of Erasmus Medical Center in the Netherlands, and the other by Yoshihiro Kawaoka of the University of Wisconsin) engineered the new bird flu strains. After growing the H5N1 strain for several generations, the scientists discovered the exact genetic mutations that allowed the virus to be transmitted by air between ferrets. The results could be easily duplicated if the teams publish their studies with full details.

The National Science Advisory Board for Biosecurity (NSABB), a U.S. government advisory panel that is run out of the NIH, asked the journals Science and Nature to delay publication of the research. The NIH released the following details in a press release:

Due to the importance of the findings to the public health and research communities, the NSABB recommended that the general conclusions highlighting the novel outcome be published, but that the manuscripts not include the methodological and other details that could enable replication of the experiments by those who would seek to do harm. The NSABB also recommended that language be added to the manuscripts to explain better the goals and potential public health benefits of the research, and to detail the extensive safety and security measures taken to protect laboratory workers and the public.

The request has sparked a debate about if and when it is appropriate to have oversight of dual-use research. As defined by the NSABB, dual-use research of concern is research that is “reasonably anticipated to provide knowledge, products, or technologies that could be directly misapplied by others to pose a threat to public health and safety, agricultural crops and other plants, animals, the environment or materiel.”   A good synopsis of the bioethical implications of such research is considered by Alan Rozenshtein on lawfareblog.com.

One of the research team leaders, Ron Fouchier, responded that the NSABB’s advice amounted to one-country domination of a discussion with worldwide impact. At the same time, he conceded that the mutant strain is “probably one of the most dangerous viruses you can make.” The professor who oversees biosafety for University of Wisconsin, William Mellon, responded that the research is “society’s best defense against a pathogen that has shown time and time again that, in nature, it can adapt to human hosts with dire consequences for global public health.”

Science and Nature were slower to respond. Last month, Science Editor-in-Chief Bruce Alberts noted the journal’s initial hesitation to acquiesce to the NSABB recommendation-

“We strongly support the work of the NSABB and the importance of its mission for advancing science to serve society…At the same time, however, Science has concerns about withholding potentially important public-health information from responsible influenza researchers. Many scientists within the influenza community have a bona fide need to know the details of this research in order to protect the public, especially if they currently are working with related strains of the virus.”

Nature‘s Editor-in-Chief Philip Campbell replied along the same lines:

“We have noted the unprecedented NSABB recommendations that would restrict public access to data and methods and recognise the motivation behind them. It is essential for public health that the full details of any scientific analysis of flu viruses be available to researchers. We are discussing with interested parties how, within the scenario recommended by NSABB, appropriate access to the scientific methods and data could be enabled.”

The issue at hand is as one scientist, Peter Palese, opined in Nature: “We need more people to study this potentially dangerous pathogen, but who will want to enter a field in which you can’t publish your most scientifically interesting results?”

Just last week, both teams of researchers announced in an open letter published in Science and Nature that they agreed to pause their work for 60 days. In the meantime, the teams propose to discuss the benefits and safety measures of their work in an international forum for discussion and debate within the scientific community. The researchers stated in the open letter,

“We realize that organizations and governments around the world need time to find the best solutions for opportunities and challenges that stem from the work. To provide time for these discussions, we have agreed on a voluntary pause of 60 days on any research involving highly pathogenic avian influenza H5N1 viruses leading to the generation of viruses that are more transmissible in mammals.”

Where, when and how these discussions will take place on an international level remains to be seen, but the NSABB appears to have made its point.

An unintended effect of the recommendations is that they have called into question the role and purpose of the NSABB. The NSABB was created in 2004, as a response to the 2001 anthrax attacks and the subsequent public outcry for regulation of research with implications for bioterrorism. As past president of the American Society for Microbiology, Ronald Atlas, put it, “[t]here was a sense, whether right or wrong, that if the community did not act to protect the integrity of science, government would overreach and there would be censorship.” Instead of regulating scientific research directly, the NSABB panel of scientists was given the role of offering advisory opinions on sensitive issues.

Since 2004, the NSABB has only been asked to review six papers. Two of those papers, released in 2005, described the reconstruction of the deadly 1918 influenza virus. The NSABB recommended that the papers clearly define the public-health benefits of the research, but no other advice was given. This is partly why the NSABB’s current recommendation is unprecedented.

According to Amy Patterson, director of the NIH, a draft policy for dual-use research should be presented by the U.S. government this spring. The draft should present a comprehensive framework for the oversight of such research, and create a local review component. As she states it,

“Whatever system is put in place needs to have both aspects: some consideration up front when the work is funded, but also a component of local oversight and review. It starts with the investigator — he or she knows best what is emerging out of their work. But we also need a level of institutional review to provide a second set of eyes taking a fresh look. The earlier something is recognized, the more options for management you have.”

Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, stated that the draft plan may require scientists to apply online for access to critical information, after explaining their need for details on dual-use research. As of right now, it is unclear who would judge the validity of such requests. It is worth noting that at least one other institution, the University of Maryland’s Center for International and Security Studies, has outlined potential oversight systems already.

The dilemma of dual-use research is already a global problem, and therefore requires a global solution. The World Health Organization commented after the H5N1 mutations, stating a deep concern about the possible misuses of the research. The WHO was quick to note the critical need for such scientific knowledge, but concluded that “such research should be done only after all important public health risks and benefits have been identified and reviewed, and it is certain that the necessary protections to minimize the potential for negative consequences are in place.”

As Laurie Garrett, senior fellow for global health at the Council on Foreign Relations, notes in a thorough review of international mechanisms for oversight of dual-use research, the first problem is that there are “no consistent, internationally agreed-upon regulations governing synthetic biology.” The only review that does currently exist is the “toothless” Biological Weapons Convention(BWC) from 1975, to which 165 states are party.

Last month, U.S. Secretary of State Hillary Clinton attended a BWC summit, and stated-

“The nature of the problem [dual-use research] is evolving. The advances in science and technology make it possible to both prevent and cure more diseases, but also easier for states and nonstate actors to develop biological weapons. A crude, but effective, terrorist weapon can be made by using a small sample of any number of widely available pathogens, inexpensive equipment, and college-level chemistry and biology. Even as it becomes easier to develop these weapons, it remains extremely difficult . . . to detect them, because almost any biological research can serve dual purposes. The same equipment and technical knowledge used for legitimate research to save lives can also be used to manufacture deadly diseases.”

The need for global cooperation on this issue is crucial.

In truth, it seems that pandemics fascinate most of society, and not just public health professionals. Last year saw the release of the movie Contagion, with a plot line appealing enough to enlist the acting talents of Gwyneth Paltrow and Matt Damon (for a great comparison of the movie to real-world issues, see  W. Ian Lipkin’s op-ed for the New York Times). Further, avian flu remains a present threat. Just this month, Chinese health authorities confirmed a bird-flu-related death, Indonesia reported the third death related to bird flu in three months, and there are reports of avian flu among birds in India. Given that H5N1 remains such a threat without the consideration of bioterrorism, the need for regulations on dual-use research is seemingly more apparent than ever.

New Evidence on Smoking Marijuana and Lung Function; Update on New Jersey’s Nascent Medical Marijuana Program

This week’s JAMA includes an article reporting on new evidence that smoking marijuana does not negatively affect lung function. Smoking tobacco has long been known to harm the lungs and to increase the risk of developing chronic obstructive pulmonary disease and lung cancer, both leading causes of death. The risks posed by smoking marijuana, on the other hand, have largely been assumed, based on the fact that “[m]arijuana smoke contains many of the same constituents as tobacco smoke[.]”

The authors of the JAMA article analyzed data from a 20-year longitudinal study of 5,115 people in 4 American cities who “comprise a broad cross-section of typical tobacco and marijuana use patterns” and found that “[w]ith up to 7 joint-years of lifetime exposure (e.g., 1 joint [a day] for 7 years or 1 joint [a week] for 49 years)” there was no evidence of an adverse effect on the lungs. Very heavy marijuana use in excess of 7 joint-years of lifetime exposure could prove harmful, but there were not enough heavy users in the study to demonstrate this.

High-quality epidemiological evidence like this latest JAMA study will be key to filling in the gaps in our knowledge about marijuana’s safety profile. While double-blinded randomized controlled trials are considered the gold standard for evaluating the safety and efficacy of drugs, they are not always an option, particularly where the goal is to gather data over many years. Marijuana’s classification as a Schedule 1 controlled substance adds to the difficulty of mounting clinical trials. Given this, it is (or will be) a very good thing that New Jersey’s still-nascent medical marijuana program will include a registry of de-identified patient treatment and outcomes data that will allow researchers to learn more about the drug’s safety and efficacy.

The statute authorizing New Jersey’s medical marijuana program was passed two full years ago, in January 2010, but the road to implantation has been a long and rocky one. (My previous posts on the subject are here, here, here, and here.) While the Christie Administration is now on board, local towns have proved resistant to efforts to site alternative treatment centers that would grow and/or dispense marijuana there. In the Associated Press earlier this week, Geoff Mulvihill writes that “[s]o far, only one [of the six groups authorized by the state to operate alternative treatment centers] has announced that it has secured local approvals. … Three others have been shut out of their chosen locations by local government bodies, despite assurances that security at the dispensaries would be tight and that pot would be given only to patients who are truly sick.”

The state may be fighting back. Nina Rizzo reports in the Asbury Park Press that Assemblyman Declan O’Scanlon has announced “that he will introduce legislation next week that would prohibit counties and municipalities from interfering with the development of medical marijuana cultivation and distribution centers by extending their protections under the Right to Farm Act.”

Such a heavy-handed approach may be necessary in the short term, to ensure that all six authorized alternative treatment centers can get off the ground. If the New Jersey Compassionate Use Medical Marijuana Act and its regulations work as they are intended to, however, public confidence in the program should grow.

A Call for Improved Guidance on Research with Pregnant Women

This month, the thoughts of Christians around the world turn to a laboring mother in “a stable at midnight in Bethlehem in the piercing cold.” It seems an appropriate time to direct your attention to the work of the Second Wave Initiative, “a collaborative academic effort to advocate for, and help find, ethically and scientifically responsible solutions for increasing our knowledge base for the treatment of pregnant women who face medical illness.”

At the end of October, the Initiative submitted comments on the Department of Health and Human Services’ Advance Notice of Proposed Rulemaking (ANPRM) regarding revisions to the regulations governing human participation in federally-funded research, known as the Common Rule.  The Initiative’s comments, of which I am a co-signatory, call attention to the fact that the ANPRM fails to address “vagaries and constraints” in the current regulations “that make it difficult for researchers to feel comfortable understanding the parameters of responsible research with pregnant women.”

The Initiative recommends that HHS take the following five steps.

First, amend the Common Rule to allow for research in pregnant women, fetuses, and neonates that creates a minor increase over a minimal risk of harm, as is already permitted in children. The Initiative’s comments explain that the regulations currently provide that “any research that does not carry the potential for direct health benefit to pregnant woman or fetus is disallowed unless it involves ‘no more than minimal risk.’”  Some government officials have concluded from this that even pharmacokinetic studies — which involve nothing more risky than drawing blood and which are vital to determining dosing in pregnancy — are ruled out.

Second, eliminate the requirement that, with certain delineated exceptions, fathers must consent to research that “holds out the prospect of direct benefit solely to the fetus.” The current regulations do not require paternal consent where there is a prospect of direct benefit to the pregnant woman or, oddly, where there is no prospect of direct benefit to the pregnant woman or the fetus.  The regulations governing pediatric research seem more sensible, requiring that both parents give consent where the research involves greater than minimal risk and holds out no prospect of directly benefitting the child.

Third, amend the regulations so that they no longer label pregnant women as “vulnerable.” As Seton Hall Law’s Carl Coleman has explained, the Common Rule does not define vulnerability and the examples it gives of vulnerable populations are diverse.  With regard to pregnant women, “it is not clear why any special issues related to capacity or coercion would necessarily arise.”  The Initiative recommends changing the word “vulnerable” to “population meriting special regulation.”

Fourth, confirm that HHS’ proposed changes with regard to research that is excused from ethics review and research that is eligible for expedited review encompass research with pregnant women. The Initiative contends that explicit confirmation is necessary “to avoid inappropriate exceptionalism about pregnancy on the part of researchers and institutional review boards.”

Finally, “establish and formally charge a working group to propose new model language for the special regulation of clinical research with pregnant women that strikes a more appropriate and more just balance of rights, needs, and interests.” As I explained here, “[w]e lack data on the efficacy or safety or both of most drugs when used by pregnant women. … Without denying or dismissing the real moral conundrums that arise in maternal-fetal medicine, the information gap is deeper and wider than that.”  To the extent that the Common Rule creates unjustified barriers to desperately-needed, ethically-appropriate research, revisions must be made.

Video Gamers Provide New Insights for the Design of Antiretroviral Drugs

I suppose with age comes humility and I may well owe my 17 year-old son an apology. So here it is Rich, about as publicly as I can muster: video games are not, apparently, an utter waste of time.

FierceBiotech IT  reports: “Video gamers uncover AIDS drug targets.” FierceBio writes:

Players of the online science game Foldit have pieced together the structure of an enzyme that could provide new targets for AIDS treatments, doing in three weeks what scientists failed to accomplish in more than 10 years.

The retroviral protease is a scissor-like enzyme that helps keep the AIDS virus going. Blocking the enzyme’s activity is a goal of drug researchers, but they first need to know the structure of the enzyme. Firas Khatib, a researcher at the University of Washington, where Foldit originated, gave players of the online game the challenge of cracking the structure of the protease that scientists had puzzled over for more than a decade. The players came up with multiple structures of the enzyme in an astonishing three weeks, giving Khatib and his colleagues enough information to revise the gamers’ work.

In addition, the gamers were able to expose “molecules on the surface of the enzyme that could be blocked with drugs to disable the function of it.”

Astonishing, really. If only they would continue to use their powers for good instead ….

The findings were published in Nature Structural & Molecular Biology and you can find the abstract here, Crystal structure of a monomeric retroviral protease solved by protein folding game players and the FierceBiotech IT article here

Video gamers uncover AIDS drug targets – FierceBiotechIT

The NIH’s Amended Conflict of Interest Regulations: A New, Weaker Approach to Intellectual Property Interests?

Yesterday, at long last, the National Institutes of Health released the final revisions to its regulations governing financial conflicts of interest on the part of applicants for federal research funds.  And there is good news.  The rule’s sunshine provisions have not, as was feared, been “gutted.”  Grant recipients will have to make their investigators’ financial conflicts of interest publicly accessible.  While an institution will not have to post the details of each conflict on its website, as was provided in the proposed regulations, if it does not it will instead have to provide the information in writing to anyone who asks for it.  Academics, advocates, federal and state prosecutors, other regulators, and members of the news media will have the access they need.  For sure, prospective patients or research participants will be less likely to come across information about investigator conflicts, but, as Kathleen Boozang explains here, it is far from clear that they would find such information helpful.

Of potentially more significance than the weakened sunshine provisions, the final regulations diverge from the proposed regulations with regard to the treatment of intellectual property.  Under the prior regulations, investigators were required to inform their institutions about relevant intellectual property rights, including copyrights, patents, and royalties in excess of $10,000.  The proposed regulations modified the definition to require disclosure of copyrights, patents, and royalties (and agreements to share in royalties) regardless of amount.  Under the final regulations, investigators do not need to tell their institutions about their intellectual property rights and interests unless and until they are in “receipt of income related to such rights and interests.”

The preamble to the final regulations is somewhat confusing.  For example, while the final regulations define significant financial interest to exclude intellectual property rights and interests that do not produce income, the agency states in the preamble that it “would expect institutional policies to require disclosure upon the filing of a patent application or the receipt of income related to the intellectual property interest, whichever is earlier.”  The preamble also contradicts itself with regard to the applicability of the rule’s $5,000 threshold, stating at one point that the threshold “applies to licensed intellectual property rights (e.g., patents, copyrights), royalties from such rights, and agreements to share in royalties related to licensed intellectual property rights,” while explaining (correctly, I think) at another point that “the $5,000 threshold would apply to equity interests and ‘payment for services,’ which would include salary but not royalties.”

The NIH’s explanation of its addition of the “receipt of income related to such rights and interests” qualifier to the definition of a significant intellectual property right or interest is especially confusing.  The agency writes that its intent was to exclude from the definition

“the rare cases when unlicensed intellectual property is held by the Investigator instead of flowing through the Institution,” because “it is difficult to determine the value of such interests.”  The agency’s point about valuation may be true, but that is an argument in favor of disclosure not against it.  With regard to equity interests, the final regulation requires investigators to disclose any equity interest in a non-publicly traded entity; the Food and Drug Administration similarly requires disclosure of equity interests “whose value cannot be readily determined through reference to public prices[.]“  The FDA also requires disclosure of any “[p]roprietary interest in the tested product,” without regard to value.

When an investigator has a proprietary interest in a product under study the potential exists for a serious conflict regardless of the interest’s current value or whether it is currently income-generating.  Seton Hall Law’s Center for Health & Pharmaceutical Law & Policy and others have recommended a near-total ban on serving as an investigator in that case.  Such a ban cannot, of course, be implemented unless investigators are required to tell their institutions about their proprietary interests.

The Changing Landscape of Health Information Regulation

There is an impressive new issue of the American Journal of Law & Medicine out, with top names in the field participating in a symposium entitled “Marketing Health: The Growing Role of Commercial Speech Doctrine in FDA Regulation.”  I also wanted to recommend a piece from Simon Stern and Trudo Lemmens on pharma ghostwriting, which is getting a lot of play in Canada.  Titled “Legal Remedies for Medical Ghostwriting: Imposing Fraud Liability on Guest Authors of Ghostwritten Articles,” the piece could lead to some interesting litigation opportunities.  Here is the abstract:

Ghostwriting and guest authorship of medical journal articles raise serious ethical and legal concerns, bearing on the integrity of medical research and evidence used in legal disputes. Ghostwriting involves undisclosed authorship, usually by medical communications agencies or a pharmaceutical sponsor of the published research; guest authorship involves taking authorial credit for the published work without making a substantial contribution to it. Commentators have objected to these practices because of concerns involving bias in ghostwritten clinical trial reports and review articles. We also note the effects of ghostwritten articles on questions involving the legal admissibility of scientific evidence. Efforts to curb ghostwriting practices, undertaken by medical journals, academic institutions, and professional disciplinary bodies, have thus far had little success and show little promise.These organizations have had difficulty adopting and enforcing effective sanctions, for specific reasons relating to the interests and competencies of each kind of organization.

Because of those shortcomings, a useful deterrent in curbing the practice may be achieved through the imposition of legal liability on the ‘guest authors’ who lend their names to ghostwritten articles. We explore the doctrinal grounds on which such articles might be characterized as fraudulent. A guest author’s claim for credit of an article written by someone else constitutes legal fraud, and may give rise to claims that could be pursued in a class action based on the Racketeer Influenced and Corrupt Organizations Act (RICO). The same fraud could support claims of “fraud on the court” against a pharmaceutical company that has used ghostwritten articles in litigation. This doctrine has been used by the U.S. Supreme Court to impose sanctions on the authors and corporate sponsors of a ghostwritten article. We discuss the potential penalties associated with each of these varieties of fraud.

This promises to inspire some difficult legal challenges to industry practices that have long been considered undesirable as a policy matter.

Recommended Reading: Recent Legal Scholarship on Decision-Making about Health and Healthcare

In Health Choices: Regulatory Design and Processing Modes of Health Decisions, Orly Lobel and On Amir briefly summarize a fascinating series of experiments they have conducted with the support of the Robert Wood Johnson Foundation that test individuals’ ability to make decisions about their health in the face of cognitive depletion or overload.  A longer version will be available in September, but the summary is well worth reading.  Lobel and Amir begin by reviewing a line of research demonstrating, perhaps unsurprisingly, that “psychological depletion caused by a prior task” — in one study it was eating radishes while resisting cookies–leads to a reduced ability to exercise “executive control” and “persist in demanding cognitive activities.”  As the authors note, applying this research to the context of health related decision-making is important because patients and providers alike are frequently asked to process information about relative risk and make reasoned, reasonable decisions under conditions of cognitive depletion or overload.

To test their hypothesis that “absent sufficient resources for executive functions individuals will take more risk in their [health-related] decisions,” Lobel and Amir conducted a lab experiment with approximately 700 participants and a web-based one with over 3000 participants, including 300 medical doctors.   The findings from their studies support the conclusion that depletion affects people’s ability to process risk, albeit not in entirely intuitive or predictable ways.  For example, when parents are cognitively depleted, they become more risk averse regarding vaccinating their children, but when policymakers are cognitively depleted, they become less risk averse regarding population-wide vaccination.  When consumers are in a state of attention and focus, a long list of potential side effects will deter them from using a new drug.  When cognitively overloaded, though, they paid “less attention to warning lists the longer they were.”  The implications of Lobel and Amir’s work are many, varied, and vast; I am looking forward to reading the full paper when it comes out in September.

I also highly recommend Christopher Tarver Robertson’s Biased Advice, which was published in the Emory Law Journal earlier this year.  Robertson conducted a series of experiments that built on the groundbreaking 2005 study by Daylian M. Cain, George Loewenstein & Don A. Moore evaluating the effect of a conflict of interest, and of disclosure of the conflict, on the quality of advice given by advisors regarding the number of coins in a jar and on the accuracy of advisees’ estimation of the number of coins in the jar.  Cain and his colleagues’ most surprising finding was that when a conflict existed, disclosing it caused the accuracy of advisees’ estimates to decline, in part because advisors gave more biased advice when their conflicts were disclosed than when they were not disclosed.

Among other questions, Robertson examined whether a more concrete disclosure about an advisor’s bias–that is, that “prior research has shown that advisors paid in this way tend to give advice that is $7.68 higher on average than the advice of advisors who are paid based on accuracy”–would aid advisees.  It did not, because advisees did not do what “one would hope and expect” and simply subtract $7.68 from the advisor’s estimate.  Rather, it appears that they “used the bias disclosure not as a mechanism of calibrating their reliance more precisely, but rather as a strengthened warning suggesting that the advice is altogether worthless.”

On the other hand, disclosing to advisees that an advisor was paid based on the accuracy of the advisee’s estimate–i.e. that the advisor’s financial interest aligned with that of the advisee–led advisees to rely more heavily on the expert’s advice and, as a result, to more accurately estimate the number of coins in the jar.  Disclosure of a conflict of interest is also likely to be valuable where advisees can seek out another advisor; a second, unconflicted, opinion dramatically increased the accuracy of advisees’ estimates.

Robertson’s research is important and interesting.  As he observes, one of the reasons that it is so difficult to rein in health care costs is that “[t]he health care industry is characterized by radically distributed decision making, with each patient deciding upon her own course of treatment within the range of treatments offered by providers and covered by public and private insurers.”  Improving individual decisions may be key to bending the cost curve.  Robertson’s research suggests that a disclosure mandate could help under certain circumstances, where, for example, there is “epistemic charlatanism” and a physician’s disclosure of a financial conflict of interest would lead a patient to reject the physician’s not-so-expert recommendations.  Robertson emphasizes, however, that disclosure does not improve layperson decision-making nearly as much as unbiased advice does.

Can’t Teach an Old Doc New Tricks?

Reuters reports that,

According to findings in the American Journal of Medicine, patients whose doctors had practiced for at least 20 years stayed longer in the hospital and were more likely to die compared to those whose doctors got their medical license in the past five years.

The study, which was based in Montefiore Hospital in the Bronx, NYC, examined the records of over 6,500 patients of the teaching hospital from 2002 to 2004. Over the course of the study, there were 59 different attending physicians heading up 6 different teams, consisting of said attending, a medical student, and recent med school graduates.  A junior doctor randomly assigns patients to a team. The researchers grouped patients and according to length of practice for the attending– “five years or less,
six to 10 years, 11 to 20 years, or more than 20 years.”

Reuters reports,

At first glance, compared to patients with the newest doctors, those with the most experienced physicians had more than a 70 percent increase in their odds of dying in the hospital and a 50 percent increase in their odds of dying within 30 days.

However, when the researchers took into account how sick the patients were, they
found that only the sicker patients — those with complicated medical problems — were at higher risk in the hands of the more experienced doctors.

So… the good news here is that only sicker patients are at higher risk in the hands of the more experienced doctors. Those with complicated medical problems are more likely to die if seen by a more experienced doctor. Although I feel as though I should write this again, I fear it still won’t fully resonate. But let me try in simple, quasi-mathematic terms:  More sick + More Experienced Doctor = More Death.

No, it’s still not working for me, but Reuters spoke with Dr. Niteesh Choudhry of Harvard Medical School, who was not involved in the study but is said to have offered the following:

The problem, he said, is not with the capability of the more experienced doctors, but rather, their familiarity with more current guidelines and practices. The results suggest the need to rethink the way doctors are continually educated in the years after completing their certification, he added.

There’s more, and you can read it here.

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