Richard is talking about post-trial responsibilities. He points out that there is a justice issue here with ensuring access to health care and up to date interventions. He points out that while the FDA can encourage Post-Trial Access (PTA), it has no authority to require or ensure it. He points to moral authority, rather than legal. Foreign trials, however, are a different story, as the FDA has sway over protocol applications that are submitted in the US. Richard begins highlighting some specific considerations for protocol drafters and IRBs: particularly focusing on determining monitoring plans, as well as figuring out financial responsibilities for the provision of PTA.
He moves on to highlight that there is more of a moral obligation than a legal obligation. FDA is supportive of the provision of PTA. He believes that enthusiasm must be tempered, as there are situations when PTA is not appropriate. These include studies that have significant safety concerns, studies of bio-markers as well as validation studies that do not specifically examine safety and effectiveness. There are also situations where PTA is simply not feasible, particularly if additional drugs do not exist (one thinks of the recent Ebola treatment), if there is insufficient safety data, or if there is no practical capacity or resources to provide safety monitoring. We must also be aware of financial limitations, especially for start-up biotech firms that might not have deep pockets.
Art Caplan has a new video on Medscape laying out the principles behind rationing limited supplies of experimental ebola treatments. As he explains:
I believe the answer to the question of who should receive the drug is: people we can both learn from and potentially help the most. I believe those are the 2 values we use when trying to ration access to an experimental drug. If we do not learn whether something is safe and effective, then we have missed an opportunity, even in the middle of an epidemic, to find out whether it is worth giving out drugs that are new, untested, and unapproved. People who should be included are those who can be observed and kept under surveillance — not for a day or a week but probably for months and years. That favors people who are not in rural villages. That favors people who will have access to hospital facilities. Those criteria will drive the selection of who receives a new, unapproved drug.
It is important that the WHO committee affirmed the morality of compassionate use. This addresses the concern that any use of unapproved drugs is inherently exploitative. But there are huge ethical issues that still remain unaddressed and unanswered regarding experimental interventions.
In the wake of the Canadian government’s offering 1,000 doses of an experimental Ebola vaccine to the stricken nations, he also extends the argument from allocation of treatment to allocation of prophylaxis in this opinion piece in NBC News Health:
It is ethically appropriate in the midst of a deadly contagious epidemic to try both untested treatments and experimental preventative vaccines that have shown some promise in animals and no safety issues. But with only 1,000 doses of vaccine available, who should get them? And what do they need to be told?
The most ethical way to distribute limited experimental vaccine, is, as the WHO ethics group noted, with an eye toward collecting information on safety and efficacy. Rather than just handing out vaccine to a small group of people in countries that have seen Ebola outbreaks, it is important to learn as much as possible about whether the vaccine has any efficacy in humans and is safe.
Amidst news from Spain that a 75-year-old Catholic priest has received the experimental treatment ZMapp for Ebola, Art Caplancritiques what he describes as the “bad science” behind choosing its recipients:
ZMapp is not the answer to the Ebola epidemic ravaging West Africa. There is no chance of getting a significant amount of this drug made for many months. Deploying more health care workers, face guards, moon suits, gloves and antiseptic, along with restrictions on travel and burying the dead, is the only way to get the epidemic under control. [...]
The fact that a 75-year-old has been given the scarce drug is especially disturbing, not because he is 75 but because 75-year-olds do not have strong immune systems — something very important in battling a virus like Ebola. Moreover 75-year-olds often have other medical problems that complicate the ability of scientists to figure out if the drug is safe and if it is really working.
In testing unapproved, highly risky drugs like ZMapp, it is crucial that recipients not be so sick that they may well die regardless of whether they get the drug or not. Indeed, the recipients ought not be very sick so that side-effects can be seen and efficacy determined. To do that, doctors need to be able to monitor experimental subjects for months to make sure the drug does not damage their livers or cause any other fatal side-effect. So not every person infected with Ebola makes for the best recipient — younger, those more recently infected and those who can be closely monitored are among the “best” candidates.
You can read more of Art Caplan’s perspective on NBC News Health here.
Earlier this week, the World Health Organization, responding both to the international outcry over the rapidly rising number of Ebola cases and deaths across sub-Saharan Africa (and critiques of the speed of their action), and the news that western health care workers and ministry had found ways to get access to the untested-in-humans Ebola drug ZMapp, convened a panel of ethicists to offer recommendations on more widespread use of experimental Ebola treatments.
1) Whether it is ethical to use unregistered interventions with unknown adverse effects for possible treatment or prophylaxis. If it is, what criteria and conditions need to be satisfied before they can be used?
2) If it is ethical to use these unregistered interventions in the circumstances mentioned above, then what criteria should guide the choice of the intervention and who should receive priority for treatment or prevention?
In 2012, the FDA introduced a novel pathway for expedited review of breakthrough therapies. The ‘breakthrough-drug’ designation was carved out by the Food and Drug Administration Safety and Innovation Act (FDASIA), which provided for expedited development and review of any drug “intended, alone or in combination with 1 or more other drugs, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on 1 or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.” This pathway added to a variety of other accelerated FDA approval programs aimed at improving access to innovative, safer, or more effective therapies for serious medical conditions.
In a recent New England Journal of Medicine article, Jonathan Darrow, Jerry Avorn and Aaron Kesselheim examine the clinical consequences and ethical dimensions of the breakthrough-drug category, and raise a variety of vital questions about its implications for patients.
My wonderful HLS colleague Matthew Stephenson has just launched the Global Anticorruption Blog (GAB). As it happens, his first two posts may be of interest to BOH readers, especially those may be of interest to readers interested in international aid for public health projects, of the sort supported by the Gates Foundation. The first post argues that the extent of corruption in these projects is much larger than the Gates Foundation and others acknowledge. The second post contends that one reason for lowballing of corruption estimates is political: these projects depend substantially on public funding, and political support for health aid may be undercut by candid assessments of the extent of the corruption and fraud problems. Both the posts and the blog are well worth a read.
Kevin Outterson appeared on NPR’s “Here & Now” to discuss the growing problem of antibiotic resistance and possible ways to incentivize development of new antibiotics. From the interview:
On the misuse of antibiotics
“We should think of this as a global resource that needs to be conserved and taken care of. So antibiotics should never be used inappropriately. In the country right now, we have something on the order of 23 million people who are getting antibiotics for ear aches. Most of those situations would resolve on their own in a couple of days. We also give antibiotics many times for people just because they have some sort of a common cold — it’s estimated 18 million prescriptions a year — doesn’t help anyone who has the common cold. It’s a complete waste.”
On the rise of antibiotic-resistant bacteria
“It’s frightened people for more than a decade. You mentioned at the top the 23,000 Americans who are dying from resistant infections. The CDC said on top of that, there’s another 14,000 dying from a horrible disease, intestinal disease, called Clostridium difficile [C-diff] in the United States. Together, that’s larger than the number of people who die in this country each year from AIDS. And we’re not — as bad as things are now, the more troubling aspects, or what might happen in five or 10 years if some sort of a pathogen was resistant to everything we had got out to the population. It sounds like a Hollywood movie.”
During the government shutdown in October 2013, a battle in part over the future of healthcare reform, a non-negligible amount of media attention focused on the shutdown of public parks. Perhaps because the parks were the least expected casualty of the shutdown, or the most ludicrous – many are, after all, large outdoor spaces that functioned for millions of years before there were federal funds for them – Americans were frustrated or amused that they could not walk around outside some places because politicians in D.C. could not agree on a budget.
The healthcare reform debate pitted those who believed that everyone should have health insurance or that access to healthcare was a right against those who believed that health spending was already too high or that everyone does not have a right to access to healthcare. In a world of infinite resources, where everyone could have complete access to healthcare without anyone having to give up anything of their own, it is difficult to imagine that anyone would say that there should not be universal access to healthcare, that some are not deserving of the service. It would be strange to require a threshold public showing of effort to obtain health insurance through employment if there was no cost to giving the healthcare – if fairness is an issue, as it appears to be a concern for some, there are certainly other services that could be denied. It is likely that for most the fairness concern only becomes salient in the face of resource constraints where these same funds could fund other programs or allow others to pursue their interests.
On December 12, a bipartisan bill entitled the Excellence in Diagnostic Imaging Utilization Act of 2013 (HR 3705) was introduced in the House of Representatives which would require clinicians to use electronic clinical decision support tools (CDS) before ordering advanced diagnostic imaging tests for Medicare patients. Structured around appropriate use criteria developed by professional medical societies, the tools would aim to increase the value of advanced imaging studies by informing and guiding practitioners’ decisions across a variety of clinical settings.
Such tools would provide active feedback on the appropriateness and evidence base of various imaging modalities, and would require physicians to furnish rationales for ordering tests that are inconsistent with appropriate use criteria. The bill also envisions the creation of registries that document how diagnostic tests are used in order to facilitate research and to enable feedback to clinicians on metrics related to appropriate use criteria. In a press release, the American College of Radiology lauded the proposed legislation, stating that it would “revolutionize the specialty of radiology.”
Mandating the use of electronic clinical decision support tools portends at least three key improvements in clinical workflows and healthcare quality more broadly.
Human rights disaggregates otherwise related issues into separate rights. We discuss rights to health, education, housing, association, etc., and, in countries where these rights are codified, we litigate each one separately in the courts. We also know that each of these issues for which there is a corresponding right is, to some extent, a symptom of poverty. In some cases it might not be possible to treat the symptoms without addressing the root cause. For example, in 1966, the Coleman study on equality in education found that “[s]chools bring little inﬂuence to bear on a child’s achievement that is independent of his [or her] background and general social context.” These findings have been contested, but it is likely that socioeconomic factors are a determinant of a child’s academic success, along with the educational experience itself. If the socioeconomic background is the greater determinant, it may not make sense to use scarce government resources to fund school improvement rather than addressing poverty itself. In a country with a right to education, school improvement could be litigated and potentially derail national efforts to address root causes.
It is estimated that 500,000 patients are discharged from U.S. hospitals against the recommendations of medical staff each year. This category of discharges, dubbed discharges against medical advice (DAMA), encompasses cases in which patients request to be discharged in spite of countervailing medical counsel to remain hospitalized. Despite safeguards that exist to ensure that patients are adequately informed and competent to make such decisions, these cases can be ethically challenging for practitioners who may struggle to balance their commitments to patient-centered care with their impulse to accomplish what is in their view best for a patient’s health.
Writing in the most recent issue of JAMA, Alfandre et al. contend that “the term ['discharge against medical advice'] is an anachronism that has outlived its usefulness in an era of patient-centered care.” They argue that the concept and category of DAMA “sends the undesirable message that physicians discount patients’ values in clinical decision making. Accepting an informed patient’s values and preferences, even when they do not appear to coincide with commonly accepted notions of good decisions about health, is always part of patient-centered care.” The driving assumption here seems to be that if physicians genuinely include patients’ interests and values in their assessments, then the possibility of “discharge against medical advice” is ruled out ab initio, since any medical advice issued would necessarily encapsulate and reflect patients’ preferences. They therefore propose that “[f]or a profession accountable to the public and committed to patient-centered care, continued use of the discharged against medical advice designation is clinically and ethically problematic.”
While abandoning DAMA procedures may well augment patients’ sense of acceptance among medical providers and reduce deleterious effects on therapeutic relationships that may stem from having to sign DAMA forms, it leaves relatively unaddressed the broader question of how to mitigate health risks patients may experience following medically premature or unplanned discharge. Alfandre and Schumann’s robust interpretation of patient-centeredness also raises the question of how to handle situations in which patients refuse medically appropriate discharge. On this interpretation, can the ideal of patient-centered care be squared with concerns for optimizing the equity and efficiency of resource allocations more broadly?
Aaron Kesselheim is a physician and an Assistant Professor of Medicine at the Harvard Medical School. He will be speaking at the Petrie-Flom Health Law Workshop on Monday, November 18, at 5:00pm, on “Do March-In Rights Protect Public Interests in Medical Products Arising from Federally-Funded Research?”
For more details on the workshop, including information on how to obtain a copy of the paper, please visit the Petrie-Flom Center’s website.
Evaluating Effective Charities with Elie Hassenfeld of GiveWell
How can you maximize the impact of your charitable giving? What distinguishes the most effective causes and organizations? Elie Hassenfeld, co-founder and co-Executive Director of GiveWell, will describe how his organization is revolutionizing charity evaluation with completely transparent, rigorous analysis. Q&A to follow.
Elie Hassenfeld graduated from Columbia in 2004 and co-founded GiveWell in mid-2007 where he currently serves as co-Executive Director. GiveWell finds outstanding charity and publishes the full details of its analysis to help donors decide where to give. The Boston Globe has called GiveWell “The gold standard for giving” and its research has attracted attention from Peter Singer and other media. GiveWell has tracked over $10 million in donations to its recommendations as a direct result of its research.
Please join the Petrie-Flom Center for a lecture by Neil Flanzraich on responsible pricing strategy, access to care, clinical trial design, outsourcing, and other topics that raise thorny but crucial issues for pharmaceutical and biotechnology companies. There will be substantial time for Q&A.
Mr. Flanzraich graduated from HLS in 1968, and was appointed by Dean Martha Minow as an Expert in Residence at the Harvard Innovation Lab (i-lab) in fall 2012. He is the Executive Chairman of Kirax Corporation and the Executive Chairman of ParinGenix, Inc., both of which are privately owned biotech companies. He previously served as the Vice Chairman and President of Ivax Corporation, an international pharmaceutical company, which was sold to Teva in 2006 for an enterprise value of $10 billion.
It is clear that EMTALA aims to prevent hospitals from dumping patients that require emergency care until these patients are stabilized. But whether EMTALA also prevents hospitals from hoarding emergency patients to their detriment is far less clear. Recently, the Tenth Circuit confronted this question in Genova v. Banner Health, a case concerning a physician who claims that he was fired for complaining about overcrowding at his emergency room. The physician sought protection under EMTALA’s whistleblower provisions, which prevent hospitals from taking an “adverse action” against an employee simply because that employee “report[ed] a violation of a requirement of [EMTALA].” Thus, the question for the Tenth Circuit was whether a hospital violates EMTALA if it has an overcrowded emergency room and refuses to offer a transfer to its waiting patients. Writing for a unanimous panel, Judge Gorsuch held that there was no such violation.
As a matter of statutory purpose, the Tenth Circuit had a persuasive case. After all, EMTALA is clearly intended to prevent hospitals from dumping its emergency patients onto other hospitals to avoid the costs of providing uncompensated care. So when Dr. Genova complained about “patient hoarding” rather than “patient dumping,” the court cleverly stated that “[h]is complaint wasn’t about an EMTALA violation but more nearly its inverse.” Indeed, there are serious potential issues with finding that EMTALA requires any overcrowded hospital to transfer its patients. Such a rule might allow hospitals, which are often overcrowded, to use resource constraints as an excuse for transferring patients that require expensive care.
But the Tenth Circuit rested much of its case on the statutory text. And as a matter of statutory interpretation, this issue is far from clear. EMTALA states that a hospital which receives a patient “must provide for an appropriate medical screening examination within the capability of the hospital’s emergency department.” If a patient has an “emergency medical condition,” the hospital must provide either (A) “within the staff and facilities available at the hospital, for such further medical examination and such treatment as may be required to stabilize the medical condition,” or (B) “for transfer of the individual to another medical facility in accordance with subsection (c) of [EMTALA].”
Anthony Stokes, a fifteen year old kid from Decatur County, Georgia, is expected to die in a matter of months, according to his doctors at the Children’s Healthcare of Atlanta. Maybe, they say, he will live for six months. Who knows? Anthony suffers from an enlarged, increasingly less functional heart. His condition is not unusual, and a reasonably effective cure is at hand: a heart transplant. (Learn more about Anthony’s story here.)
However, Anthony has become the latest victim of a dysfunctional U.S. transplantation system, which tempts Americans with a transplant waiting list, but kicks them off if they become too sick or too old. The problem is that there are too few organs to meet demand, and this perennial problem receives far too little attention from Congress. Indeed, the U.S. transplantation list, coordinated by the United Network for Organ Sharing, UNOS, (a private organization that coordinates significant aspects of the U.S. transplant system) is so overcrowded that patients increasingly turn to black markets in India, China, Pakistan, South Africa, and other countries if they hope to survive. (Learn more about that here.) Congressional hearings document Chinese prisoners dying and shortly thereafter Americans receiving organs.
Anthony’s family and some local organizations claim that racism is behind doctors refusing to place the boy on the transplant list. Anthony is African American. They ask, what is the harmin letting him on the list?
Remember the long fight over whether Sarah Murnaghan, the little 10-year-old girl from suburban Philadelphia who was dying from cystic fibrosis, should have a shot at getting a transplant from lungs taken from an adult? The fight hinged in part on whether there was sufficient evidence to show that adult lungs would work as well in Sarah, who is still struggling to recover from two lung transplants, as they would in another adult where they would fit better. Some, including me, argued that the best way to allocate scarce lungs for Sarah or anyone else is to determine who is most likely to live if they get them.
That may seem a sensible ethical policy to use when there are not enough organs for all. But there is a new study out that calls into question the merits of an efficacy-only rationing policy.
In the wake of our seemingly everlasting economic crisis, the Spanish health authorities have decided to exclude single women to access ART treatments – mainly artificial insemination- in the public health care system. “The lack of a male partner is not a medical problem”, has said Ana Mato, our Secretary of Health. Coming from a devout Catholic and extremely conservative politician, her remark, and ultimately, her Department’s policy, have been widely interpreted as another vindication of the idea that only traditional, i. e. heterosexual, families are suitable for rearing children. The spokeswomen of various feminist and lesbian NGOs have entered the public arena to denounce her lesbophobia.
The fact of the matter is that women in Spain, whether married to another woman or single, will still be authorized to be artificially inseminated (in some European countries such as France, Austria or Sweden, for instance, single women are excluded from medically assisted reproduction). Even the fertile, married heterosexual woman might still get artificial insemination – maybe she just wants to do things differently, for a change- although they will all have to bear the costs. The public health care system has, therefore, reconfigured ART as a pure medical remedy for a medical condition: infertility. The days of IA as an “alternative means of reproduction” for “alternative life-styles” are over. But with this new policy the demand made by economically disadvantaged lesbian couples willing to procreate finds an answer along the following lines: “go find a male”. A crude response if there is one. Continue reading →
On May 29th, HHS issued the final rule governing wellness incentives in group health plans. While the incentives themselves are not a surprise, the scope they are given is worthy of ongoing attention. Wellness incentives have been controversial because of their potential for intrusion into individual choice, their subtle (or not so subtle) coerciveness, their valorization of a particularly model of health, and the possibility that they will impose differential burdens and costs on people with disabilities or other disfavored groups. The final rule attempts to meet these objections in several helpful ways.
Nonetheless, the final rule still will allow programs that are differentially burdensome as a result of factors other than health status. It will also allow programs under which it is more difficult for some than for others to obtain rewards because of their states of health. In programs that give rewards for health outcomes, alternatives must be available for those who do not meet targets—but the reasonableness standard for these alternatives permits requirements that may be differentially burdensome so if they are medically appropriate and follow the recommendations of the patient’s personal physician. HHS supports wellness programs as engaging individuals in their health, as encouraging them in healthy behaviors and discouraging them in unhealthy behaviors, and as incentivizing people to make use of recommended health care services such as screenings. Continue reading →