The future of reproduction: King’s Alumni event

The future of reproduction: Where do we draw the line? on Tuesday 25 November 2014, 18.45 – 21.00, Anatomy Lecture Theatre (K6.29), 6th floor King’s Building, Strand Campus, WC2R 2LS.

This is the first event of the ethics series for King’s Alumni which will explore and debate important ethical issues.  Professor Bronwyn Parry (Professor in Social Science, Health & Medicine and Director of Undergraduate Studies) and Professor Rosamund Scott (Professor of Medical Law and Ethics and Co-Director, Centre of Medical Law and Ethics) will speak on paid surrogate motherhood in low- and middle-income countries, such as India, and the use of reproductive technologies to select the sex of one’s child, respectively.  Dr Annette Rid (Senior Lecturer in Bioethics and Society) will host the evening.

Quoted in Science Magazine

Jon Cohen: Issues continue to dog the testing of Ebola drugs and vaccines (16 Oct 2014)

At a U.S. congressional hearing today that examined the country’s public health response to Ebola, an official from the Food and Drug Administration (FDA) said it’s working to develop “a flexible and innovative protocol” to evaluate experimental treatments for the disease. The fact that no such common protocol already exists speaks to the complex practical and ethical issues that surround the use of untested drugs and vaccines in the midst of explosive spread of a virus that kills more than half the people it infects.

Given the epidemic’s unprecedented scale, a panel of bioethicists and infectious disease specialists convened by the World Health Organization (WHO) in August unanimously decided that it was ethical to use unproven treatments and preventions against this deadly disease. The panel also said there was a “moral obligation” to gather and share scientifically relevant data about whether these products were safe and effective. But it did not suggest how this should happen, and as the FDA official’s testimony indicated, new views are still emerging while others are being refined.

Over the past few months, subsequent WHO consultations and opinion pieces by prominent public health experts and ethicists have spelled out detailed visions of how to proceed with testing of experimental Ebola medicines. The issues, both practical and ethical, are starkly different for drugs and vaccines. Unproven drugs go to the sick, who are fighting for their lives and often have few options, whereas experimental vaccines are tested in healthy people—most will be first-line workers—in an effort to protect them from the deadly virus. “Ethical arguments are not the same for all levels of risk,” noted 17 prominent researchers and ethicists from 11 countries in an editorial about Ebola drug testing published online on 10 October in The Lancet.

The gold standard of clinical trial design for both drugs and vaccines is the randomized controlled trial (RCT), in which half the participants are randomly assigned to receive the experimental medicine, while the control group receives conventional care, sometimes including a placebo. Doctors Without Borders (MSF), which has treated more Ebola patients in West Africa than any other group, emphatically opposes RCTs in affected countries for either treatments or vaccines. MSF’s Annick Antierens, who oversees “investigational platforms” for experimental Ebola products, says “this cannot be defended ethically.”

The Lancet editorial, led by Piero Olliaro of WHO and the United Kingdom’s University of Oxford, sided with MSF with regard to treatments. In making their case, the authors question the meaning of “equipoise,” a fundamental ethical principle behind RCTs that says investigators should not know whether an intervention is better than what’s offered to the control group. “Equipoise is a useful principle, but it can break down when conventional care offers little benefit and mortality is extremely high,” the authors write. “This is precisely the problem with Ebola: current conventional care does not much affect clinical outcomes and mortality is as high as 70%. When conventional care means such a high probability of death, it is problematic to insist on randomising patients to it when the intervention arm holds out at least the possibility of benefit.”

The editorial rebuts an article published online on 11 September in The Journal of the American Medical Association by bioethicist Steven Joffe of the University of Pennsylvania (Penn) and an earlier one by bioethicists Annette Rid of King’s College London and Penn’s Ezekiel Emanuel that ran online on 21 August in The Lancet. Those authors contend that “compassionate use” of experimental Ebola medicines outside of RCTs, as has happened in a few patients with the antibody cocktail called ZMapp and a drug made by Tekmira, risks compromising the ability to gather scientific evidence and, as Joffe writes, “will not necessarily prevent more deaths than would administration of the drug in a well-designed clinical trial.”

Rid says Olliaro and co-authors wrongly assume that receiving an experimental treatment is necessarily better than receiving effective supportive care—which has not been available to many infected people in West Africa. She further contends that the editorial “underplays the possibility that experimental interventions can make people worse off” and “neglects the population-level concern that, even if the interventions don’t make individuals worse off, they may be ineffective and we would end up misallocating scarce resources.”

The design of real-world studies to test whether Ebola vaccines work has similarly triggered impassioned discussions. Many researchers at a WHO consultation held 29 and 30 September came to the meeting thinking that traditional RCTs were off the table: Sentiment seemed to be leaning toward a strategy known as stepped-wedge that would give all participants the Ebola vaccine at different points in time and then look to see whether people who received it later were more vulnerable to infection. But at the meeting, Ripley Ballou from GlaxoSmithKline (GSK), which has the Ebola vaccine furthest in development, won wide support for his argument that the fastest, most ethical way to assess whether the product works is with an RCT that uses an “active control”—such as a proven vaccine against an unrelated disease—rather than a dummy placebo shot.

In the wake of that meeting, some have questioned whether an active control is more ethical than a placebo. Peter Smith, an epidemiologist at the London School of Hygiene & Tropical Medicine who attended that meeting as well as a 2013 WHO consultation on the use of placebos in vaccine trials, contends the issue is practical, not ethical: An active control may persuade more participants to join the study. “If it’s easier to do the trial if you use an active control rather than a placebo, then fine, do the trial that way,” Smith says. “But to believe one is more ethical than the other is not the issue.” He stresses that the main benefit of joining a vaccine trial, especially in resource-strained countries like these, is that people who do develop the disease “are generally looked after better than people not in trials.”

Arthur Caplan, a bioethicist at New York University in New York City who co-authored the latest Lancet editorial opposing RCTs for Ebola drugs, supports their use for Ebola vaccines. But he worries that an active control may cause problems. Immune responses triggered by the vaccine in the active control arm, he notes, “could complicate interpreting the results” in people who received the Ebola vaccine. It also raises ethical dilemmas if an active control arm uses a vaccine that the country cannot afford to use routinely.

Bioethicist Nir Eyal of the Harvard School of Public Health in Boston, who also supports RCTs for Ebola vaccines, says it’s “an enormous privilege” to be offered a chance to participate in a trial that gives people a 50% chance of receiving a vaccination with some promise of success. “Of course nobody wants the placebo,” Eyal says. “But the point of medical trials is not to provide the intervention that’s medically best for the research subject. It’s to establish something that’s important—and this point is crucial—for a far larger population and to prevent human catastrophe.”

Even MSF does not rule out other trial designs that offer the Ebola vaccine to all participants. Aside from the stepped-wedge scheme, researchers could stage less rigorous “observational” trials, which are typically used after vaccines come to market to see how well they work in entire populations. “After licensure, there are plenty of observational studies that give us very, very useful and meaningful results that we believe,” says epidemiologist Arthur Reingold of the University of California, Berkeley.

In this scheme, vaccine is distributed without an organized study and investigators would look at Ebola rates in a cohort of vaccinated people—say, the health care workers at one hospital—or assess vaccination rates in people who develop Ebola. “The key issue when you start calculating vaccine effectiveness is whether people who get the vaccine and people who don’t get the vaccine are relatively comparable,” Reingold says.

Yet another hot-button issue is who should be eligible to receive experimental drugs or treatments. Scarce treatments like ZMapp have preferentially gone to health care workers because, as the August WHO consultation emphasized, they put their lives at risk for others and they are needed to control the epidemic. Rid and Emanuel question whether this makes sense, noting that health care workers have special ties to the medical community and relatively higher levels of income. “Their priority might therefore be viewed as further privileging of the already well-off, especially by contrast with those who provide care without being trained as health professionals.”

On the vaccine front, GSK may have up to 20,000 doses ready for efficacy tests in January, but that still means there likely will be far more interested participants than product. The latest WHO consultation says front-line workers should go first—not just doctors and nurses—a group that includes anyone who helps care for patients or even buries those who die.

For practical reasons, meeting participant Michael Selgelid of Monash University, Clayton, in Australia says it makes the most sense to offer the vaccine to the “traditionally conceived” notion of a health care worker. “They are best able to give proper informed consent, and it’s crucial in this scenario that we have really good informed consent,” he says. At the end of the day, Selgelid says, regulators like FDA likely will heavily influence trial design as they are the ones who will ultimately decide whether these products can come to market. “Just how flexible the regulators are going to be is a question for them rather than me,” he says.

Monash Bioethics Review: joining Editorial Board

As of October, I’ll be serving on the Editorial Board of Monash Bioethics Review – which has just been relaunched with Springer. Submissions encouraged!

Monash Bioethics Review

Editors-in-Chief: J. Oakley, M.J. Selgelid

  • An international forum for empirically-informed philosophical bioethical analysis with policy relevance.
  • Includes empirical studies providing explicit ethical analysis and/or with significant ethical or policy implications.
  • One of the oldest bioethics journals, produced by a world-leading bioethics centre.

Produced since 1981 by Monash University Centre for Human Bioethics, this journal offers detailed coverage of traditional and emerging topics in bioethics, focused especially on empirically-informed philosophical bioethical analysis with policy relevance.

Indexed in: PubMed/Medline, PubMed, SCOPUS, EMBASE, Google Scholar, CSA Environmental Sciences, OCLC, Summon by ProQuest, TOC Premier

Published online: Setting risk thresholds in research

Rid A: Setting risk thresholds in research: Lessons from the debate about minimal risk. Monash Bioethics Review (in press)
(.pdf)

Abstract: One of the fundamental ethical concerns about biomedical research is that it frequently exposes participants to risks for the benefit of others. To protect participants’ rights and interests in this context, research regulations and guidelines set out a mix of substantive and procedural requirements for research involving humans. Risk thresholds play an important role in formulating both types of requirements. First, risk thresholds serve to set upper risk limits in certain types of research (e.g. pediatric research that offers the participating children no prospect of clinical benefit). Second, risk thresholds serve to demarcate risk categories that streamline risk-adapted systems of ethical oversight (e.g. expedited or no prospective ethical review of minimal risk research). But although risk thresholds play such an important role in research governance, there is a need both to better define the existing risk thresholds and to delineate new thresholds in order to develop more risk-adapted systems of research oversight. The present paper examines the existing minimal risk threshold and the surrounding debates with the goal of deriving a systematic approach to setting thresholds of research risk.

Jonathan Montgomery delivers inaugural lecture for Bioethics & Society programme

Professor Jonathan Montgomery
Public Bioethics and the Challenges of Legitimation

Inaugural lecture for the Bioethics & Society programme, Department of Social Science, Health & Medicine, King’s College London

Welcome by Professors Denise Lievesley and Nikolas Rose

Tuesday, 7 October 2014

5:30-6:30 pm    “Meet & Greet” (Great Hall Entrance Hall, King’s Building, Strand Campus)
6:30-8:00 pm     Lecture (Nash Lecture Theatre, K2.31,  King’s Building, Strand Campus)
8:00-9:30 pm     Reception (Great Hall Entrance Hall, King’s Building, Strand Campus)

publicbioethics.eventbrite.co.uk


Jonathan Montgomery
 is Chair of the Nuffield Council on Bioethics (the nearest the UK has to a national bioethics committee), and of the Health Research Authority (which protects and promotes the interests of participants, patients and the public in health research and aims to streamline its regulation). He is also a member of the panel of advisers to the Morecambe Bay Investigation, due to report in late 2014.

Previous national chair roles include the Advisory Committee on Clinical Excellence Awards (2005-14) and the Human Genetics Commission (2009-12). He served on local NHS boards in Hampshire and the Isle of Wight for over twenty years up to March 2013 (fifteen as a chairman). He chaired the UK Clinical Research Collaboration Working Party on a Strategy for Brain Tissue Banking, was a member of the Committee on the Ethical Aspects of Pandemic Influenza and the Organ Donation Taskforce (for its work on presumed consent in 2008). He has contributed to a wide range of professional guidelines and was a member of the Medical Ethics Committee of the British Medical Association from 2003 to 2008.

He is Professor of Health Care Law at the University College London (UCL). His recent publications include ‘Reflections on the Nature of Public Ethics’ (2013), 22 Cambridge Quarterly of Healthcare Ethics, 9-21 and ‘Hidden law-making in the province of medical jurisprudence’ (2014), 77(3) Modern Law Review, 343-378 (with C Jones and H Biggs). He was consulting editor for Volume 30(1) Medical Professions of Halsbury’s Laws of England (5th ed 2011) and has been one of the General Editors of the Butterworths Family Law Service since 1996

You can read more about Jonathan Montgomery’s research at http://bit.ly/1pCpvWh. You can also follow Jonathan on twitter @prof_JonMont

Bioethics and the Challenges of Public Legitimation (Abstract)

Bioethics can be considered in many ways. It is, at least, (a) a field of study, whereby we can identify exciting, interesting and controversial topics that make for stimulating enquiry; (b) an academic discipline or disciplines, whereby scholarship is brought to bear on these issues; and (c) a set of governance challenges in the public square. This lecture looks at the challenges of legitimation through the lens of the practices adopted by governance bodies, particularly in the UK. It identifies a range of legitimation strategies and considers some of the issues that they raise. While they are not entirely separate from each other, it suggests that they raise distinct, although overlapping questions that help illuminate what is needed for bioethics governance to play successfully its role in the biopolitics of the age.

Patients’ priorities for treatment decision making during periods of incapacity: new paper in Palliative & Supportive Care

Rid A, Wesley R, Pavlick M, Maynard S, Roth K, Wendler D: Patients’ priorities for treatment decision-making during periods of incapacity: Quantitative survey. Palliative & Supportive Care (in press) (.pdf)

Objective: Clinical practice aims to respect patient autonomy by basing treatment decisions for incapacitated patients on their own preferences. Yet many patients do not complete an advance directive, and those who do frequently just designate a family member to make decisions for them. This finding raises the concern that clinical practice may be based on a mistaken understanding of patient priorities. The present study aimed to collect systematic data on how patients prioritize the goals of treatment decision making.

Method: We employed a self-administered, quantitative survey of patients in a tertiary care center.

Results: Some 80% or more of the 1169 respondents (response rate = 59.8%) ranked six of eight listed goals for treatment decision making as important. When asked which goal was most important, 38.8% identified obtaining desired or avoiding unwanted treatments, 20.0% identified minimizing stress or financial burden on their family, and 14.6% identified having their family help to make treatment decisions. No single goal was designated as most important by 25.0% of participants.

Significance of Results: Patients endorsed three primary goals with respect to decision making during periods of incapacity: being treated consistent with their own preferences; minimizing the burden on their family; and involving their family in the decision-making process. However, no single goal was prioritized by a clear majority of patients. These findings suggest that advance care planning should not be limited to documenting patients’ treatment preferences. Clinicians should also discuss and document patients’ priorities for how decisions are to be made. Moreover, future research should evaluate ways to modify current practice to promote all three of patients primary goals for treatment decision making.