Mother’s Day Maternal Health Update

Pregnant Woman, Moralis Yannis, 1948 (Image by Tilemahos Efthimiadis via Flickr)

Inspired to act to reduce maternal mortality after she survived a postpartum hemorrhage, renaissance woman Christy Turlington has been making the rounds promoting her documentary No Woman No Cry, which tells the stories of at-risk pregnant women in Bangladesh, Guatemala, Tanzania, and the United States.  If you have been in a Starbucks lately you may have seen the compilation compact disc of the same name, the proceeds of which support the advocacy organization Turlington founded, Every Mother Counts.  As Turlington writes, “almost all of the hundreds of thousands of maternal deaths that occur each year are preventable. Yes, 90 percent!”

While the developing world bears the brunt of the global burden of maternal mortality and morbidity, the United States is not immune.  Women in 49 other countries have a better chance of surviving childbirth.  Passage of the Maternal Health Accountability Act of 2011, which was introduced by Representative John Conyers (D-MI) on March 3, 2011 and is currently pending in the House Committee on Energy and Commerce’s Subcommittee on Health, would be an important step towards redressing the problem of maternal mortality and morbidity here at home.

Among other things, the Act would provide funds to states to improve the reporting and tracking of pregnancy-related deaths.  In a recently-released report, the Council of State and Territorial Epidemiologists noted that maternal & child health “is the one program area in which overall state-level epidemiology and surveillance capacity increased progressively from 2004 to 2009, bucking the trend of an overall decrease in state-level epidemiology capacity.”  On the other hand, “the MCH epidemiology capacity glass is only half full: nearly half of all states lack even substantial MCH epidemiology and surveillance capacity, and in only a minority of jurisdictions do MCH epidemiologists participate substantially in policy development; have access to important data sets; and work with colleagues in substance abuse, mental health, and occupational health.”

The Maternal Health Accountability Act would also direct the National Institutes of Health to “organize a national workshop to identify definitions for severe maternal morbidity and make recommendations for a research plan to identify and monitor such morbidity in the United States.”  As the Act’s findings section explains, “[s]evere complications that result in women nearly dying, known as a ‘near miss’ or severe morbidity, according to some estimates, increased by 25 percent between 1998 and 2005, to approximately 34,000 cases a year. However, there is no scientific consensus on uniform definitions of severe maternal morbidity and best practices for data collection, making it difficult to measure the full extent of severe morbidity and developing evidence-based interventions.”  Finally, the Act would direct the Secretary of Health and Human Services to conduct research and establish demonstration projects targeting the stark geographic, racial, and socioeconomic disparities in maternal health outcomes.  According to Amnesty International’s Spring 2011 Deadly Delivery report, “[n]ew government data shows that for 2005-2007, the maternal mortality ratio (deaths per 100,000 live births) was highest among non-Hispanic black women (34.0), followed by American Indian/Alaska Native women (16.9), Asian/Pacific Islanders (11.0), non-Hispanic whites (10.4), and Hispanics (9.6).”

Importantly, tackling the problem of maternal mortality and morbidity need not wait until Congress acts.  In an article in the April issue of the American Journal of Obstetrics & Gynecology, Hospital Corporation of America, a chain of 114 inpatient facilities that claims to be the “largest obstetrical health care delivery system in the United States,” reported on its highly-successful obstetric patient safety program.  Among other things, HCA expanded the number of free, online programs it offers on topics such as fetal heart rate monitoring, postpartum hemorrhage, and shoulder dystocia, with the goal of educating providers and ensuring that they use “common terminology and thus avoid potentially hazardous miscommunication.”  In addition, HCA engaged in process standardization efforts including the development of checklist-based protocols and supported the development of national quality metrics to facilitate benchmarking.  HCA has been effective at reducing elective delivery before 39 weeks gestation and it “instituted a policy of universal perioperative pneumatic compression device use in all patients undergoing cesarean delivery.”  (I discussed the latter intervention here.)  HCA reports that its efforts have paid off, not just in outstanding perinatal outcomes, but also in reductions in litigation, as reflected by reported claims.  In 2009, the company’s losses due to “accidents on hospital grounds” exceeded its losses due to maternal mortality and morbidity.  Even more impressive, its “perinatal loss (in dollars) … is rapidly approaching the level of loss seen in the category ‘occupational therapy.’”

HCA opines “that adoption of our approach on a national level could, within 5 years, both dramatically reduce adverse perinatal outcomes and to a large extent eliminate the current national obstetric malpractice crisis.  In reality, a relatively small number of repeated errors lead to most preventable adverse outcomes, and may be reduced by the approaches outlined above.”  The company is not optimistic that its approach will be widely adopted, however, because it believes that efforts to improve perinatal outcomes have been hindered by “an alternative culture in which physician autonomy and anecdotal experience trump available data and the recommendations of the Institute of Medicine, contributing to a ‘normalization of deviance’ at odds with a safety-based culture.”  I wonder how physicians would respond to this interesting and provocative claim.  Might they argue that hospital policies and practices are at least in part to blame for our stalled efforts to reduce maternal mortality and morbidity?

Center News: Greater Newark Healthcare Coalition, Improving Care Through Collaboration

The Greater Newark Healthcare Coalition is now in its second year and continues to pursue cooperative projects to improve health care for the most vulnerable in the Greater Newark area. Professor John Jacobi serves as the Coalition’s board chair. Other members include a range of health providers, consumer groups, and government agencies. The projects include:

Case management of frequent utilizers of hospital emergency departments. These very fragile patients will benefit from a sophisticated evaluation of their needs and referral to appropriate community placements. Professor Jacobi and Research Fellow and Lecturer in Law Kate Greenwood are working with clinicians on this project, and will produce analysis supporting a reconfiguration of health care funding to both improve care and reduce costs.

Improved prenatal care. The Newark area has a disproportionate number of mothers with poor access to prenatal care.The Coalition is working to bring together various organizations to improve prenatal care.

Preparing physicians for new practice models. Accountable care organizations and patient- centered medical homes require the increased adoption of technology and physician practice patterns that mesh with demands for quality and efficiency. The Coalition will conduct training sessions for area physicians.

The Center’s faculty and students are engaged and committed to lending expert support to the Coalition through legislative and regulatory advocacy and policy development, believing that the fruits of health reform will reach the most vulnerable only if providers, advocates, and regulators work together in cities like Newark.

After Makena: Could a Risk Corridors Approach Balance Incentives and Access?

The past few weeks have been worrying ones for expectant mothers who wanted a hormonal treatment designed to stop preterm births. As Rob Stein of the WaPo explains,

A form of progesterone known as 17P was used for years to reduce the risk of preterm birth. . . Because no companies marketed the drug, women obtained it cheaply from “compounding” pharmacies, which produced individual batches for them [at about $20 each]. Doctors and regulators had long worried about the purity and consistency of the drug and were pleased when KV won FDA’s imprimatur for a well-studied version, which the company is selling as Makena.

The list price for the drug, Makena, turned out to be a stunning $1,500 per dose. That’s for a drug that must be injected every week for about 20 weeks, meaning it will cost about $30,000 per at-risk pregnancy. . . . The approval of Makena gave the company seven years of exclusive rights, and KV immediately fired off letters to compounding pharmacies, warning that they could no longer sell their versions of drug.

A day after Stein’s article appeared, the FDA made it clear that it “does not intend to take enforcement action against pharmacies that compound” 17P, “in order to support access to this important drug, at this time and under this unique situation.”

This is a fascinating, and in some ways, troubling response to the accusations of price-gouging by KV. Compounding pharmacists had already averred that “many of [KV's] assertions that the compounding of an FDA approved product is prohibited are not supported by the legal citations it references.” Though the FDA’s letter preserves access to 17P for now, that access could be revoked at any time. As the FDA states on its website:

FDA understands that the manufacturer of Makena, KV Pharmaceuticals, has sent letters to pharmacists indicating that FDA will no longer exercise enforcement discretion with regard to compounded versions of Makena. This is not correct. In order to support access to this important drug, at this time and under this unique situation, FDA does not intend to take enforcement action against pharmacies that compound hydroxyprogesterone caproate based on a valid prescription for an individually identified patient unless the compounded products are unsafe, of substandard quality, or are not being compounded in accordance with appropriate standards for compounding sterile products. As always, FDA may at any time revisit a decision to exercise enforcement discretion.

Moreover, the problem persists for at least one other drug, colchicine. As Arthur Allen explains at Slate,

The colchicine and [17P] stories have their roots in the FDA’s historically complex relationship with the drug industry. Since 1962, the agency has required that all new drugs be proven safe and efficacious before hitting the market. Many drugs marketed before 1962, however, remain on sale without having been formally approved by the FDA and are technically illegal. In 2006, the FDA launched the Unapproved Drugs Initiative, aimed at getting rid of as many of these drugs as possible. . . .

The FDA campaign has two approaches. In some cases, the agency simply warns companies to stop producing and shipping unlicensed drugs by a given date. In other cases the FDA warns a group of companies producing a particular class of drug, notifying them that it plans to crack down on their unapproved substances. The idea here is to give the companies an opportunity to submit their drugs to the rigorous testing required for FDA approval. This is what happened with . . . at least 86 newly approved drugs. The problem is that after submitting such drugs to expensive testing, drug makers typically jack up the prices, in a position to do so under congressional patent incentives aimed at producing innovative drug research. The FDA has no say in how a drug is priced.

As the Post notes, KV says it “is spending more than $200 million to develop the drug and conduct follow-up studies that the Food and Drug Administration demands.” Had it kept its pricing power, it was estimated that Makena would cost the US health care system $4 billion per year. Assuming that 3/4 of that would be revenue to Makena, and it lasted for the full 7 years of exclusivity, that would be a $21 billion return on a $0.2 billion investment. That seems excessive, especially given that KV didn’t develop the drug. On the other hand, if the Makena price were to be reduced one hundredfold, that’s a $0.21 billion return on a $0.2 billion investment. Unless we hit some serious deflation, that doesn’t cover the time value of the money invested in studies and development.

Are there any better models here? Stein’s story says that “experts said the FTC could sue KV if it concludes the company is illegally impairing competition,” but I don’t see the theory there. The FTC has lamented post-merger price hikes for life sustaining drugs (see FTC v. Lundbeck), but has precious little authority over price hikes here. Perhaps liberal constitutional law professors could fuse the “medical self-defense” theory of Eugene Volokh with the expansive Yoo/Vermeule/Posner theories of executive power, and find inherent executive authority here to save preemies? Probably not; the current Supreme Court is only receptive to creative con law from one side of the political spectrum.

Another idea is for legislation to create “risk corridors” for researchers who engage in the FDA’s Unapproved Drugs program, as CMS has for prescription drug insurance plans in Medicare Part D. As Kip Piper explains,

Using a system of risk corridors that compares actual incurred drug benefit costs to estimated costs submitted in bids, Medicare limits the profits and losses of Part D drug plans. Specifically, if a Medicare drug plan’s actual benefit costs exceed expected (bid) levels by a sufficient degree, the plan will receive an additional federal payment to cover a portion of the loss. However, if a drug plan’s actual spending falls sufficiently below projections, the plan must share some of the profit with the feds. Risk corridors apply to actual and expected drug benefits costs but exclude plan administrative costs and federal reinsurance payments.

Unfortunately, estimates of the value of testing unapproved drugs vary widely. The FDA’s director of the FDA’s Office of New Drugs and Labeling Compliance insists on the importance of these programs. But, looking specifically at colchicine, an Austin rheumatologist said “Doing one trial in patients and a few drug interaction studies doesn’t justify marketing exclusivity and a 50-fold increase in price.” As Allen puts it, we need “legislative remedies to improve the drug supply without costing the public an arm and a leg.”

In health care finance, the “cost-shift” hydraulic is a familiar model. When policymakers cut reimbursements for, say, Medicare or Medicaid, providers still have the same income target, and respond by raising prices for the privately insured. One scholar estimated that the privately insured pay over 120% of costs, while Medicare payments are between 95 and 99%. We might think of pharmaceutical patents as another manifestation of “cost-shifting,” from the future (which will enjoy drugs in the public domain) to the present (which must pay the monopolist’s price). Other forms of exclusivity can also lead to that type of cost-shift, as the Makena controversy makes clear. Perhaps the people most benefited by a regime of pharmacovigilance and evidence-based medicine should be asked to pay something for that new reassurance. But they shouldn’t be price gouged. A risk corridors approach might better balance patients’ interests in research on, and reasonable prices for, unapproved drugs.

Solving the Mysteries of Pregnancy

Photo by Johann Nojhan Dreo via Flickr

In last week’s JAMA, the Pandemic H1N1 Influenza in Pregnancy Working Group reported that their analysis of nationwide data on 2009 influenza A (H1N1) in pregnant women revealed that “early antiviral treatment appeared to be associated with fewer admissions to an ICU and fewer deaths.”  Pregnant women who were not treated with antiviral medication until 3-4 days after they began experiencing flu symptoms were more likely to die than those who were treated within 2 days of symptom onset.  Women who were first treated with medication more than 4 days after symptom onset were 54 times more likely to die than those who were treated within 2 days.

The authors speculate that the “reasons for delayed treatment … could include reluctance of pregnant women or clinicians to use antiviral medication because of concern for risk to the fetus, despite available evidence suggesting that treatment benefit likely outweighs the potential risk.”  Given the shocking 54-fold increased risk of death associated with late initiation of antiviral medication, the authors’ use of the qualifiers “suggesting” and “likely” is noteworthy.  They are forced to hedge because, as a group of experts convened by the CDC acknowledged in late 2009, “[l]ittle is known about the effects of the four currently available influenza medications on the fetus.”

In my article The Mysteries of Pregnancy: The Role of Law in Solving the Problem of Unknown But Knowable Maternal-Fetal Medication Risk (forthcoming in the University of Cincinnati Law Review), I point out that this information gap is not unique to antivirals.  We lack data on the efficacy or safety or both of most drugs when used by pregnant women.  A frequent shorthand explanation for the dearth of information is that you cannot test drugs on pregnant women because of ethical concerns.  Without denying or dismissing the real moral conundrums that arise in maternal-fetal medicine, the information gap is deeper and wider than that.  As Ruth Faden puts it: “Everyone thinks, Oh, my God, research on pregnant women!  All kinds of ethical flags go up.  We don’t have to start with high drama.  [There's enough] low-hanging fruit that we could keep lots of medical researchers busy for a long time.”

Two FDA-led efforts promise to begin connecting the dots: the Medication Exposure in Pregnancy Risk Evaluation Program, which will conduct epidemiological research using data on approximately 1 million births gathered by the 11 participating research sites, and the Sentinel Initiative, which is creating a national electronic system with the goal of, among other things, allowing for prompt investigation of the safety of newly-approved drugs in pregnant women.  Other government agencies also have roles to play.  For example, the house committee report accompanying the Departments of Labor, Health and Human Services and Education Fiscal 2010 Appropriations measure encouraged the NIH “to  expand research on pregnant women with the goals of better understanding the long-term health effects on women of disease states in pregnancy, the proper therapeutics for pharmacologic treatments for pregnant women who face illness, and the safety and efficacy of medications administered to pregnant women and fetuses.”   Finally, industry can and should do more.  Congress should empower FDA to require pharmaceutical companies to sponsor maternal-fetal medication research in appropriate cases, authority the agency already has in the pediatric arena.

Rising Maternal Death Rate: A Sentinel Event

Photo by Boliston via Flickr

California Watch, a project of the Center for Investigative Reporting, reported earlier this month that the rate of maternal deaths directly related to pregnancy and birth nearly tripled in California between 1996 and 2006– from 5.6 maternal deaths per 100,000 live births to 16.9 per 100,000.  Even after accounting for improved information gathering, the rate has more than doubled and “[c]hanges in the population — obese mothers, older mothers and fertility treatments — cannot completely account for the rise … said Dr. Elliott Main, the principal investigator for the task force” that prepared the report.  While the reason or reasons for the rise in deaths are not yet understood, Dr. Main notes that the rate of Cesarean sections increased by 50 percent over the 1996-2006 time period.

Sadly, California is unlikely to be unique in this regard.  Maternal death rates have probably increased in other states and in the country as a whole as well.  On January 26th, the Joint Commission issued a Sentinel Event Alert to hospitals, notifying them that “current trends and evidence suggest that maternal mortality rates may be increasing in the U.S.”  The Commission acknowledged that that incidence of maternal death remains low — at an estimated 13.3 deaths per 100,000 live births — and that a possible reason for the increases seen is better identification of women who die during or shortly after pregnancy.  Still, the Commission quoted the CDC’s Dr. William M. Callaghan as follows: “[T]here clearly has been no decrease in maternal mortality in recent years, and we are not moving toward the U.S. government’s Healthy People 2010 target of no more than 3.3 maternal deaths per 100,000 live births[].”  Moreover, “[m]aternal deaths are the tip of the iceberg for they are a signal that there are likely bigger problems beneath — some of which are preventable,” says Dr. Callaghan. “It is important to consider the women who get very, very sick and do not die, because for every woman who dies, there are 50 who are very ill, suffering significant complications of pregnancy, labor and delivery.”

Not all maternal deaths are preventable, of course.  To reduce the rate of those that are, the Joint Commission suggests a number of actions for hospitals and physicians to take, including participating in state-level maternal mortality reviews and developing protocols (and holding drills to train staff on the protocols) for responding to conditions such as hemorrhage and pre-eclampsia.  More concretely, the Commission quotes Dr. Steven L. Clark of the Hospital Corporation of America who argues that the “only cause of maternal death amenable to nationwide systematic prevention efforts is pulmonary embolism [a blood clot in the lung].”  Disappointingly, while nearly all adult patients undergoing major surgery receive prophylactic measures for the prevention of venous thromboembolism (VTE) — even patients with no risk factors for the condition — pregnant women undergoing Cesarean delivery traditionally do not, despite the fact that they are at increased risk.   In light of the Commission’s Sentinel Event Alert, it seems to me that hospitals would be well-advised to adopt VTE prophylactic measures for all pregnant women undergoing Cesarean sections at once.  Is there a downside I am missing?