Filed under: Children's Issues, 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.
President Obama has begun the process for healthcare reform by improving access through insurance reform, but achievement of his aspirations will require reform of our healthcare delivery system as well. Changing where and how healthcare is delivered and paid for is of particular importance given the emerging and generally non-acute needs of the aging baby-boomers, and the lack of sufficient primary care to serve the many who will become insured as health insurance reforms are implemented. Healthcare providers realize this, and the market is indeed adjusting as we speak.
Three examples of these changes to the delivery system include, first, moving much of the delivery of services out of hospitals and into the community. Healthcare systems are rapidly affiliating with or employing physicians to facilitate this change, in the hopes of enabling the various parts of the health care system to work more collaboratively, efficiently and cost-effectively. In many parts of the country, hospitals have been too cash-strapped to invest in necessary updating to their hospital facilities. Now that we are thinking differently about how to use the physical plant that hospitals occupy, and investing in new technology, these investments need to happen. As a third example, President Obama is infusing money into hospitals and physician offices to enable the United States to catch up to other developed nations in the digitizing of its medical records. The benefits of this change are numerous, but it is a very expensive transformation.
In order to provide quality service and compete in the fast-changing healthcare market, hospitals and the systems of which they are a part, need money to pay for these changes. A February 21, 2012 New York Times article on the expansion of Catholic hospitals provides a glimpse of this phenomenon of market reform. Cash-poor hospitals unable to access capital to invest in the new initiatives necessary to keep them competitive are looking for financially stronger partners with this investment ability. There are currently 56 Catholic healthcare systems in the country, ranging from the financially successful to the distressed. Thus it is unsurprising that a potential partner for some hospitals might be found among Catholic systems. Read more
A February 21, 2012 New York Times article entitled “Catholic Hospitals Expand, Religious Strings Attached” addresses the challenges that arise when Catholic healthcare systems acquire healthcare providers and extend religious proscriptions to the newly acquired facilities and practitioners. Specifically, the article raises concerns about women’s access to reproductive health services, particularly in communities where Catholic ownership of hospitals and other providers dominates. Much of this same kind of market activity occurred in the early 90′s in anticipation of market reforms associated with Clinton healthcare reform. So, while these are not new issues, they are no less difficult to resolve, perhaps in part because we have all become more politicized in our approach to problem solving, which almost seems impossible to imagine, but there it is. In a 1995 Houston Law Review article entitled DECIDING THE FATE OF RELIGIOUS HOSPITALS IN THE EMERGING HEALTH CARE MARKET I attempted to propose a middle ground of accommodation that would facilitate access to care while providing Catholic healthcare providers with the space required to continue to be true to their religious beliefs. I believe that the prescription remains as valid today as it was when written over a decade ago.
Catholic healthcare comprises a ministry, whereby the sisters or diocese that provide the health services are committed to ensure that they act in way that is true to the teachings of the Catholic Church. Catholic healthcare providers are living the gospel, which is replete with instances of Jesus ministering to the sick — he attended to healing the mind, body and spirit. This holistic healing mission began when various religious orders first established their hospitals, and continues today, albeit with fewer religious and more laypersons continuing the legacy of the Catholic healthcare mission. Catholic healthcare has served an essential role in the United States since the nation’s inception, frequently being the only provider of care to the poor in numerous communities. That dedication to the vulnerable segments of society continues today. Catholic healthcare providers were the first in many communities to treat compassionately, without judgment and without discriminating, those with HIV/AIDS. Mission statements for Catholic providers focus on ensuring care to the homeless, to immigrants, whether documented or not, and to the underserved and uninsured. According to statistics available on the Catholic Health Association web page, Catholic healthcare is a national leader in its provision of birthing rooms and breast cancer treatment, geriatric services, nutrition programs, social work services and pain management programs. The disappearance of Catholic hospitals would decimate access to care in rural communities. Catholic hospitals have long been on the forefront of the call for healthcare reform that provides access to all, and support President Obama’s health reform efforts.
Catholic hospitals’ delivery of healthcare is informed by Catholic Social Teaching broadly and specifically by what are called The Ethical and Religious Directives for Catholic Health Care Services, which are promulgated by the United States Conference of Catholic Bishops. Catholic Social Teaching rests on centuries of philosophical and theological learning to guide not only the Church but society in general on such questions as the relationship between labor and capital, the respectful treatment of employees and the importance of unions to workers, distribution of goods and services, and human rights to social goods such as health care. The Ethical and Religious Directives, which are informed by Catholic teaching, are moral guidelines specific to healthcare, to aid in resolving such ethical issues as pregnancy termination, contraception, and euthanasia. Obviously, the clinical situations in which these guidelines are implicated can be extremely complex, and sometimes require nuanced analysis by those with a deep understanding of Catholic moral theology and medicine. Like any intellectual discipline, theologians, bishops, and healthcare providers sometimes disagree among themselves as to the appropriate application of these guidelines to a specific situation. So, yes, it is true that Catholic healthcare providers are committed by their religious beliefs to operate in ways that may be different than secular providers, but these differences extend far beyond the moral limitations on the kinds of reproductive and end-of-life care they provide. This moral framework serves to unleash the kind of compassionate care that has been a hallmark of Catholic healthcare since its inception. Even in the face of severe budget cuts, Catholic hospitals continue to provide pastoral care to their patients, caregivers, and families; engage in constant assessment of fidelity to mission; and have been leaders of all hospitals with regard to measuring tax-exempt facilities’ provision of community benefits.
My ultimate point is two-fold. First, Catholic healthcare is too important to the country’s healthcare system to be reduced in our assessment of its value to religious proscriptions that may interfere with access to a limited universe of services, albeit what are sometimes characterized as essential healthcare services. While some may dissent from application of Catholic teaching in particular instances, the continued and pervasive presence of health providers committed to the dignity of every person whom they treat is an ultimate societal good. Where disagreement persists, it is important that the Church engage in sincere dialogue with all segments of society, with a willingness to be informed from medical, ethical, and sociological perspectives.
As Catholic providers partner, merge or otherwise collaborate with secular healthcare providers, community stakeholders, including licensing agencies, should demand and receive a clear understanding of the implications for healthcare access of the proposed alliance. Each bishop acts as the ultimate arbiter of the Ethical and Religious Directives, which means that interpretations can vary by diocese. For example, a minority of bishops have raised questions about the kind of emergency care administered by hospital emergency departments to rape survivors, out of an over-abundance of medical and moral caution, in my view, that the treatment might interfere with a pregnancy. Thus, it is essential that regulators understand the implications of Catholic teachings for healthcare access, so that patients clearly understand the limitations of Catholic providers and, where appropriate, have alternatives to access services. Our healthcare system has and will likely always be extremely pluralistic. We have, and should continue to make every effort, to accommodate the religious beliefs of providers, while ensuring access to care to which patients are legally entitled.
Further, the public debate about what kind of care should be legally available should take seriously the perspective of those whose viewpoints are informed by moral concerns, whether those concerns arise from religious or philosophical principles. Finally, both The United States Catholic Conference and individual bishops should ensure that they receive a robust analysis of ethical issues related to healthcare from the Church’s best theologians with relevant expertise before promulgating guidance to those engaged in healthcare ministry. Importantly, bishops should also hear from those who are involved daily in caring for and ministering to patients.
The ultimate goal of reform is one upon which both Catholic healthcare providers and proponents of women’s health agree — increased access to healthcare for all. Collaboration on the pursuit of this unified goal should enable us to identify means by which the plural interests of the stakeholders can be accomplished. Transparency and conversation are key to achieving these ends. In my conversations with those concerned about changes in the healthcare delivery system, I have always found them to be very respectful of religious freedom, appreciative of the role religious providers play in society, and desirous of finding a common way forward. While the number of religious sisters is shrinking in the United States, women remain a significant presence in the leadership of Catholic healthcare. A cursory review of the areas where Catholic healthcare predominates reveals a strong commitment to women’s health and wellness. For these reasons, I feel confident that common ground exists to ensure access to health care for all, while carving out space for Catholic fidelity to the demands of their religion.
Filed under: Drugs & Devices, Women's Health Issues
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.
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.