Filed under: Bioethics, Mental Illness, Neuroscience, Research
In April 2013, President Obama officially announced the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, with approximately $110 million in funds slated for fiscal year 2014. Identified as an Administration “Grand Challenge,” the long-term aspirations are to:
“accelerate the development and application of innovative new technologies to construct a dynamic picture of brain function that integrates neuronal and circuit activity over time and space. The goal is to build on the growing scientific foundation of neuroscience, genetics, physics, engineering, informatics, nanoscience, chemistry, mathematics and other advances of the past few decades, to catalyze an interdisciplinary effort of unprecedented scope.”
Descriptions of the Initiative emphasize the convergence of numerous technologies as playing a part in the trajectory of the research agenda. The White House Fact Sheet states that “great promise for developing such technologies [to treat neurological and psychiatric disease] lies at the intersection of nanoscience, imaging, engineering, informatics, and other rapidly emerging fields of science.” But to facilitate this, NIH acknowledges “researchers will first need a more complete arsenal of tools and information for understanding how the brain functions both in health and disease.”
The key investments to launch this initiative are to be directed through three core federal agencies: the National Institutes of Health (NIH), with a $40 million allocation for fiscal year 2014; the Defense Advanced Research Projects Agency, with a $50 million allocation; and the National Science Foundation, with a $20 million allocation. Private sector partners are the Allen Institute for Brain Science, the Howard Hughes Medical Institute, the Kavli Foundation, and the Salk Institute for Biological Studies. The White House website lists several components of the initiative, including key investments, strong academic leadership, public-private partnerships, and maintaining the highest ethical standards.
Planning is in early stages, with a BRAIN Working Group of the Advisory Committee to the Director (ACD) of the NIH formed to provide input into the development process. The BRAIN Working Group is charged with reviewing advances in neuroscience, identifying short, mid, and long-term science goals of the Initiative, and developing a scientific plan for achievement of those goals. The ACD has hosted four public hearings in San Francisco, New York, Minneapolis, and Boston to gather perspectives from the scientific community. Last week, the Working Group published an interim report with a list of nine high-priority areas for funding for FY 2014 with an “overarching vision … to combine these approaches into a single, integrated science of cells, circuits, brain and behavior”:
- Generate a census of cell types
- Create structural maps of the brain
- Develop new large-scale network recording capabilities
- Develop a suite of tools for circuit manipulation
- Link neural activity to behavior
- Integrate theory, modeling, statistics, and computation with experimentation
- Delineate mechanisms underlying human imaging technologies
- Create mechanisms to enable collection of human data
- Disseminate knowledge and training
A final report by the BRAIN Working Group is expected in June 2014.
Parallels are already being drawn to the $3.8 billion, 10-year Human Genome Project (HGP) begun in the 1990s, culminating in the publication of the complete sequence of the human genome in 2003. President Obama himself noted in his February 2013 State of the Union address that “every dollar we invested to map the human genome returned $140 to our economy.” While the HGP had many successes, it also fueled many subsequent controversies, many of which took years to play out and some that remain hotly debated today. Two high-profile examples include patent protections for inventions resulting from the HGP (see the Supreme Court’s June 2013 decision in Association for Molecular Pathology v. Myriad Genetics) and adequate privacy and genetic discrimination protections (see the Genetic Information Nondiscrimination Act).
Recognizing the broader ramifications of such a massive federal undertaking, the President has reached out to another expert task force for input. Alongside the BRAIN Working Group, the President has also directed the Presidential Commission for the Study of Bioethical Issues to “explore the ethical, legal, and societal implications raised by this research initiative and other recent advances in neuroscience.” Specifically, the Commission is to “identify proactively a set of core ethical standards – both to guide neuroscience research and to address some of the ethical dilemmas that may be raised by the application of neuroscience research findings.” An August 20, 2013 public meeting of the Commission highlighted several core ethical concerns going forward, including privacy; data protection and management; animal and human subjects research protections; potential use for enhancement purposes; stigma and discrimination; and national security. Extensive blog coverage of the public event is available here, here, and here.
Given the nascent state of the BRAIN Initiative, the overall long-term allotment of funding for research into the ethical, legal and societal implications is unclear. For the HGP, this was between 3-5% of the total budget over the life of the project. Similar research support should be built in to the Brain Initiative as well in an effort to anticipate, and guide, the ethical, legal, and societal aspects that accompany such an endeavor.
Filed under: Medical Malpractice, Quality Improvement, Research, Treatment
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.”
“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.
Filed under: Children, Research, Women's Health Issues
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.”
Filed under: CMS, Physician Compensation, Research
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, 10th 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.