Randomized control trials plus preferences: a market design for experiments by Yusuke Narita in PNAS

 Random assignment of patients to experimental treatments is intended to allow statisticians to cleanly measure the effect of the treatments. But if there is evidence that some patients might profit more from some treatment than others, fully random assignment may not maximize health outcomes. And if patients have preferences (e.g. for the risk of receiving a problematic kidney for transplant versus the risk of waiting for a better one), then fully random assignment may not maximize welfare.  Yusuke Narita thinks about how to design RCTs that elicit patient preferences and take account of prior's about outcomes, while still allowing the necessary statistical tests to determine treatment effects.

Incorporating ethics and welfare into randomized experiments  by Yusuke Narita

PNAS January 5, 2021 118 (1) e2008740118; https://doi.org/10.1073/pnas.2008740118

Edited by Parag Pathak, Massachusetts Institute of Technology, Cambridge, MA, and accepted by Editorial Board Member Paul R. Milgrom September 30, 2020 

"Abstract: Randomized controlled trials (RCTs) enroll hundreds of millions of subjects and involve many human lives. To improve subjects’ welfare, I propose a design of RCTs that I call Experiment-as-Market (EXAM). EXAM produces a welfare-maximizing allocation of treatment-assignment probabilities, is almost incentive-compatible for preference elicitation, and unbiasedly estimates any causal effect estimable with standard RCTs. I quantify these properties by applying EXAM to a water-cleaning experiment in Kenya. In this empirical setting, compared to standard RCTs, EXAM improves subjects’ predicted well-being while reaching similar treatment-effect estimates with similar precision.

...

"RCTs involve large numbers of participants. Between 2007 and 2017, over 360 million patients and 22 million individuals participated in registered clinical trials and social RCTs, respectively. Moreover, these experiments often randomize high-stakes treatments. For instance, in a glioblastoma therapy trial (1), the 5-y death rate of glioblastoma patients was 97% in the control group, but only 88% in the treatment group. In expectation, therefore, the lives of up to 9% of the study’s 573 participants depended on who received treatments. Social RCTs also often randomize critical treatments such as basic income, high-wage job offers, and HIV testing.

"RCTs, thus, influence the fate of many people around the world, raising a widely recognized ethical concern with the randomness of RCT treatment assignment: “How can a physician committed to doing what he thinks is best for each patient tell a woman with breast cancer that he is choosing her treatment by something like a coin toss? How can he give up the option to make changes in treatment according to the patient’s responses?”

...

"I propose an experimental design that I call Experiment-as-Market (EXAM). I choose this name because EXAM is an experiment based on an imaginary centralized market and its competitive equilibrium (12, 13). EXAM first endows each subject with a common artificial budget and lets her use the budget to purchase the most preferred (highest WTP) bundle of treatment-assignment probabilities given their prices. The prices are personalized so that each treatment is cheaper for subjects with better predicted effects of the treatment. EXAM computes its treatment-assignment probabilities as what subjects demand at market-clearing prices, where subjects’ aggregate demand for each treatment is balanced with its supply or capacity (assumed to be exogenously given). EXAM, finally, requires every subject to be assigned to every treatment with a positive probability.

"This virtual-market construction gives EXAM nice welfare and incentive properties. EXAM is Pareto optimal, in that no other design makes every subject better off in terms of expected predicted effects of and WTP for the assigned treatment. EXAM also allows the experimenter to elicit WTP in an asymptotically incentive-compatible way. That is, when the experimenter asks subjects to self-report their WTP for each treatment to be used by EXAM, every subject’s optimal choice is to report her true WTP, at least for large experiments.

"Importantly, EXAM also allows the experimenter to estimate the same treatment effects as standard RCTs do. Intuitively, this is because EXAM is an experiment stratified on observable predicted effects and WTP, in which the experimenter observes each subject’s assignment probabilities (propensity scores). As a result, EXAM’s treatment assignment is random (independent from anything else), conditional on the observables. The conditionally independent treatment assignment allows the experimenter to unbiasedly estimate the average treatment effects (ATEs) conditional on observables. By integrating such conditional effects, EXAM can unbiasedly estimate the (unconditional) ATE and other effects, as is the case with any stratified experiment (14)."

**********

somewhat related post:

Sunday, July 12, 2020

Incorporating patient preferences into transplant decisions can improve welfare--Genie, Nicolo and Pasini in J Health Economics

Ethics of machine learning--an interview with Michael Kearns and Aaron Roth

 Amazon Scholars Michael Kearns and Aaron Roth discuss the ethics of machine learning--Two of the world’s leading experts on algorithmic bias look back at the events of the past year and reflect on what we’ve learned, what we’re still grappling with, and how far we have to go.  By Stephen Zorio

"In November of 2019, University of Pennsylvania computer science professors Michael Kearns and Aaron Roth released The Ethical Algorithm: The Science of Socially Aware Algorithm Design. Kearns is the founding director of the Warren Center for Network and Data Sciences, and the faculty founder and former director of Penn Engineering’s Networked and Social Systems Engineering program. Roth is the co-director of Penn’s program in Networked and Social Systems Engineering and co-authored The Algorithmic Foundations of Differential Privacy with Cynthia Dwork. Kearns and Roth are leading researchers in machine learning, focusing on both the design and real-world application of algorithms.

Their book’s central thesis, which involves “the science of designing algorithms that embed social norms such as fairness and privacy into their code,” was already pertinent when the book was released. Fast forward one year, and the book’s themes have taken on even greater significance.

Amazon Science sat down with Kearns and Roth, both of whom recently became Amazon Scholars, to find out whether the events of the past year have influenced their outlook. We talked about what it means to define and pursue fairness, how differential privacy is being applied in the real world and what it can achieve, the challenges faced by regulators, what advice the two University of Pennsylvania professors would give to students studying artificial intelligence and machine learning, and much more."

What do we know about the effects of payments to participants in challenge trials for vaccines, and other public spirited activities?

There is starting to be an empirical literature associated with payments for socially productive activities, such as participating in challenge trials of vaccines, donating plasma, etc.

Here's a blog post in the Medical Ethics blog of the Journal of Medical Ethics:

Is it acceptable to pay nothing or little to challenge trial participants?  By Sandro Ambuehl, Axel Ockenfels and Alvin E Roth.   October 30, 2020

Here's a paragraph (with some links).:

"we hope that the debates about payments in medical research, and on other transactions subject to restrictions on payments such as blood plasma donations, will converge as empirical results accumulate. To date, there is empirical evidence on the underlying motivations for volunteering, on the impact of high payment on human risk taking, on decision quality and well-being, on the signal value of small payments, on strategies to evade regulation, and on the general public’s assessment of appropriate activities and  payments. Moreover, there are studies that document biases affecting normative judgment in general, and biases affecting paternalistic restrictions and moral intuitions in particular.

***********

This blog post was written in connection with our paper in the JME:

Payment in challenge studies from an economics perspective 

by Sandro Ambuehl, Axel Ockenfels, and Alvin E. Roth

published online early, Oct 28, 2020. http://dx.doi.org/10.1136/medethics-2020-

The WHO proposal for allocating scarce vaccines: thinking of healthcare while dealing with politics by discussing ethics

From the Guardian:

'Landmark moment': 156 countries agree to Covid vaccine allocation deal--Covax plan will counter rising threat of ‘vaccine nationalism’, prioritising vulnerable healthcare systems and frontline workers  by Peter Beaumont

"A coalition of 156 countries has agreed a “landmark” deal to enable the rapid and equitable global distribution of any new coronavirus vaccines to 3% of participating countries’ populations, to protect vulnerable healthcare systems, frontline health workers and those in social care settings.

"The Covid-19 vaccine allocation plan – co-led by the World Health Organization and known as Covax – has been set up to ensure that the research, purchase and distribution of any new vaccine is shared equally between the world’s richest countries and those in the developing world.

"Sixty-four higher income economies have already joined Covax, which includes commitments from 35 economies as well as the European commission, which will procure doses on behalf of the 27 EU member states plus Norway and Iceland, with 38 more expected to join in the coming days.

...

"Recognising that the first useful vaccines to emerge may be in short supply, approved vaccines will initially be made available to a tightly targeted 3% of the population of participating countries, building over time to 20% of each country’s most vulnerable population.

...

"According to a document detailing the arrangement, under the scheme “all countries should gradually receive tranches [of vaccine] to cover each subset of their [initial] target groups … until they can cover 3% of the population”.

The document continues: “At this point of the pandemic, a reasonable scenario would be that, while the supply of Covid-19 vaccines remains very scarce, countries should focus initially on reducing mortality and protecting the health system.

“This … would enable, for example, the vaccination of frontline workers in health and social care settings in most countries … Additional tranches will follow gradually as more supply becomes available.”

**************

And this from the Washington Post:

World Health Organization unveils plan for distributing coronavirus vaccine, urges cooperation    By Emily Rauhala

"Under the plan, rich and poor countries pool money to provide manufacturers with volume guarantees for a slate of vaccine candidates. The idea is to discourage hoarding and focus on vaccinating high-risk people in every participating country first.

"So far, 64 higher-income countries have signed up, WHO officials said, but they added that 38 more are expected to do so in the coming days. Notably missing: Russia, China and the United States.

"China has not made an ann"ouncement either way. The White House said this month that the United States would not join, in part because the administration doesn’t want to work with the WHO, and will instead take a go-it-alone approach.

...

"The framework makes clear that each participating country can decide whom to vaccinate first, but it is based on the idea that doses for 3 percent of a country’s population could be used to vaccinate medical workers first and then other high-risk groups.

...

"“It seems like a compromise position,” said Thomas J. Bollyky, a senior fellow at the Council on Foreign Relations and the director of its global health program. “It’s not exactly what you would do if you were driven strictly by public health.”

"In a policy report this month for the journal Science, critics offered an alternate framework called the Fair Priority Model, which is critical of the country-based approach"

************

Here's the Science article:

An ethical framework for global vaccine allocation, by Ezekiel J. Emanuel1, Govind Persad2, Adam Kern3, Allen Buchanan4, Cécile Fabre5, Daniel Halliday6, Joseph Heath7, Lisa Herzog8, R. J. Leland9, Ephrem T. Lemango10, Florencia Luna11, Matthew S. McCoy1, Ole F. Norheim12, Trygve Ottersen13, G. Owen Schaefer14, Kok-Chor Tan15, Christopher Heath Wellman16, Jonathan Wolff17, Henry S. Richardson18

"The Fair Priority Model is primarily addressed to three groups. One is the COVAX facility—led by Gavi, the World Health Organization (WHO), and the Coalition for Epidemic Preparedness Innovations (CEPI)—which intends to purchase vaccines for fair distribution across countries (5). A second group is vaccine producers. Thankfully, many producers have publicly committed to a “broad and equitable” international distribution of vaccine (2). The last group is national governments, some of whom have also publicly committed to a fair distribution (1).

...

"The Fair Priority Model proceeds in three phases, preventing more urgent harms earlier (see the Table). Phase 1 aims at reducing premature deaths and other irreversible direct and indirect health impacts. Phase 2 continues to address enduring health harms but additionally aims at reducing serious economic and social deprivations such as the closure of nonessential businesses and schools. Restoring these activities will lower unemployment, reduce poverty, and improve health. Finally, phase 3 aims at reducing community transmission, which in turn reduces spread among countries and permits the restoration of prepandemic freedoms and economic and social activities."

Global Kidney Exchange supported by the European Society of Transplantation's committee on Ethical, Legal, and Psychosocial Aspects of Transplantation .

Quite some time ago, the European Society for Organ Transplantation (ESOT) charged its committee on Ethical, Legal, and Psychosocial Aspects of Transplantation (ELPAT) with the task of evaluating those aspects of global kidney exchange (GKE). GKE had been greeted in some quarters with a number of dramatic accusations (e.g. that it was a form of organ trafficking), and the ELPAT committee tried to consider each of them.  Interestingly, the committee included members who I surmise started with a wide range of views, from cautious support to active hostility to GKE.

The final report, just published in Transplant International,  (which is the official journal of ESOT) is one that I think the committee can be proud of.  While you can tell that some committee members retain reservations about GKE, they nevertheless all agreed on a report that finds all of the principal objections raised against GKE to be unfounded.  Together with the even more clearly stated support for GKE in the Lancet, I think that this may mark a turning point: it certainly marks that GKE is receiving growing (and well deserved) support. 

Global Kidney Exchange: opportunity or exploitation? An ELPAT/ESOT appraisal
Frederike Ambagtsheer  Bernadette Haase‐Kromwijk  Frank J. M. F. Dor  Greg Moorlock  Franco Citterio  Thierry Berney  Emma K. Massey
Transplant International, September 2020, 33, 9, 989-998.    

https://onlinelibrary.wiley.com/doi/full/10.1111/tri.13630       Here's the pdf

"Summary: This paper addresses ethical, legal, and psychosocial aspects of Global Kidney Exchange (GKE). Concerns have been raised that GKE violates the nonpayment principle, exploits donors in low‐ and middle‐income countries, and detracts from the aim of self‐sufficiency. We review the arguments for and against GKE. We argue that while some concerns about GKE are justified based on the available evidence, others are speculative and do not apply exclusively to GKE but to living donation more generally. We posit that concerns can be mitigated by implementing safeguards, by developing minimum quality criteria and by establishing an international committee that independently monitors and evaluates GKE’s procedures and outcomes. Several questions remain however that warrant further clarification. What are the experiences and views of recipients and donors participating in GKE? Who manages the escrow funds that have been put in place for donor and recipients? What procedures and safeguards have been put in place to prevent corruption of these funds? What are the inclusion criteria for participating GKE centers? GKE provides opportunity to promote access to donation and transplantation but can only be conducted with the appropriate safeguards. Patients’ and donors’ voices are missing in this debate." 

Here's their introduction:

"In 2017, Rees et al. [1] introduced “Global Kidney Exchange” (GKE), an international kidney exchange program that facilitates cross‐border exchanges between immunologically incompatible donor–recipient pairs in high‐income countries (HIC) and biologically compatible but financially impoverished donor–recipient pairs in low‐ to middle‐income countries (LMIC). GKE aims to overcome immunologic barriers in the developed world and poverty barriers in the developing world. The underlying rationale is that financial barriers prevent transplantation much more frequently than organ scarcity. The number of patients dying annually worldwide from end‐stage kidney disease due to inadequate financial resources far exceeds the number of patients in developed countries placed on kidney transplantation waitlists [1-3]. GKE has the potential to expand the genetic diversity of the donor pool which may help to transplant difficult‐to‐transplant, highly immunized patients [1]."

As they debunk the main arguments that have been made against GKE, I thought that some of these remarks were among the most interesting:

"Removing financial barriers to organ donation is an internationally agreed objective, enshrined, among others, in the World Health Organization’s (WHO) Guiding Principles on Human Cell, Tissue and Organ Transplantation and in the CoE Convention [13, 15]. These organizations highlight that prohibition of organ payments does not preclude reimbursing expenses incurred by the donor, including the costs of medical procedures [13, 17]. Given that countries’ legislation vary in their approach to what constitutes illicit payment versus legitimate reimbursement, it is doubtful whether GKE violates the nonpayment principle under all circumstances. For example, the University of Minnesota’s legal team vetted GKE and agreed to proceed. Other hospital legal teams have followed suit [1]."

...

"“[e]xploitation occurs when someone takes advantage of a vulnerability in another person for their own benefit, creating a disparity in the benefits gained by the two parties” [9]. It is hard to see, however, that this description of exploitation can be readily applied to GKE. Primarily, it is not clear that there is a significant disparity in benefits between recipients. Each patient receives a kidney transplant, and as Minerva et al point out, benefits are arguably greater for LMIC recipients, who get the additional benefit of their follow‐up care being paid for [33]. The same is true for the donors, who each obtain the desired benefit of their intended beneficiary receiving a transplant. Rather than there being a morally troubling disparity in benefit, GKE appears to offer either roughly equal benefit, or greater benefit for those who are allegedly exploited."

"It is also unconvincing to consider GKE exploitative on other grounds. Rather than failing to protect the vulnerable, it seems that GKE addresses specific vulnerabilities by offering protection to those who are (i) vulnerable to death from kidney failure or (ii) vulnerable to losing a loved one due to kidney failure. It is similarly unconvincing to suggest that GKE treats people merely as a means to an end. Instead, one can see that participants in LMIC are respected as individuals, with measures put in place to protect their welfare and to ensure that their participation is voluntary."

...

The claim that donors and recipients in LMIC are too poor or vulnerable to voluntarily engage in GKE is also debatable and could be seen as paternalistic. First of all, the risk that voluntariness is undermined does not apply specifically to GKE or to LMIC alone, but applies to living donation more generally [35].

...

"The proclamation that countries have to be self‐sufficient was first declared by the 2008 DoI and the WHO [73, 74] and has rapidly gained momentum since [75-77]. The argument to ban GKE because of the need to achieve self‐sufficiency raises various implications however. First of all, it implies that the need for countries to become self‐sufficient is more important than the lives that can be immediately saved through GKE. Is achievement of self‐sufficiency so important that it overrides life‐saving alternatives? Who has the authority to decide which approach should get priority? Why is it required that countries become self‐sufficient in organ donation and transplantation, while it is universally accepted for countries to rely on global exchanges of all other types of goods and services?

 ***********************

The ESOT/ELPAT committee apparently operated under rules that prevented them from investigating some claims that required evidence, so they included some questions for us in their paper, which we answer in the comment that appeared in the same issue of TI. (For example, there was some confusion about what escrow meant in connection with the money provided for the foreign donor and recipient's medical expenses after their return home...)

In any event, the large number of co-authors to our comment (21!) is another expression of the broad and international support that GKE is achieving.

Global Kidney Exchange Should Expand Wisely
Alvin E. Roth  Ignazio R. Marino  Obi Ekwenna  Ty B. Dunn  Siegfredo R. Paloyo  Miguel Tan  Ricardo Correa‐Rotter  Christian S. Kuhr  Christopher L. Marsh  Jorge Ortiz  Giuliano Testa  Puneet Sindhwani  Dorry L. Segev  Jeffrey Rogers  Jeffrey D. Punch  Rachel C. Forbes  Michael A. Zimmerman  Matthew J. Ellis  Aparna Rege  Laura Basagoitia  Kimberly D. Krawiec  Michael A. Rees 

Transplant International, September 2020, 33, 9,  985-988. https://onlinelibrary.wiley.com/doi/full/10.1111/tri.13656   Here's a link to the pdf 

Here's the full first paragraph:

"We read with great interest and appreciation the careful consideration and analysis by Ambagtsheer et al. of the most critical ethical objections to Global Kidney Exchange (GKE). Ambagtsheer et al. conclude that implementation of GKE is a means to increase access to transplantation ethically and effectively.1,2 These conclusions by their European Society of Transplantation (ESOT) committee on Ethical, Legal and Psychological Aspects of Transplantation (ELPAT) represent a step forward toward a greater understanding and an open, honest debate about GKE. Taken together with the strong endorsement of GKE by Minerva et al. in Lancet  and the positive position statement of the American Society of Transplant Surgeons (ASTS), Ambagtsheer et al. successfully dispel previously raised doubts 5-13 to which we have previously responded .2,14-17"

************

Here are all my posts on global kidney exchange (GKE)

The ethics (and some economics) of paying participants in Human Infection Challenge Studies, for a coronavirus vaccine

 

Here's a paper (that is perhaps not too long when you divide by the number of authors) seeking to provide some background for payment decisions in connection with  human infection studies (i.e. challenge trials) of covid-19 vaccines.

Lynch, Holly Fernandez and Darton, Thomas and Largent, Emily and Levy, Jae and McCormick, Frank and Ogbogu, Ubaka and Payne, Ruth and Roth, Alvin E. and Jefferson Shah, Akilah and Smiley, Thomas, Ethical Payment to Participants in Human Infection Challenge Studies, with a Focus on SARS-CoV-2: Report and Recommendations (August 14, 2020).  

Abstract: To prepare for potential human infection challenge studies (HICS) involving SARS-CoV-2, this report offers an expert analysis of ethical approaches to paying research participants in these studies, as well as HICS more broadly. The report first provides an overarching ethical framework for research payment that divides payment into reimbursement, compensation, and incentive, focusing on fairness and promoting adequate recruitment and retention as counterweights to ethical concerns about undue inducement. It then describes variables relevant to applying this framework to any type of study, including the prospect of direct medical benefit, early participant withdrawal, study setting and location, pandemic circumstances, study budget, and participant perspectives. We conclude that there is no need for a unique payment framework specific to HICS or SARS-CoV-2 HICS, but that there may be features of particular relevance to ethical payment for these studies. Participants have varied motivations for enrolling in HICS, including financial considerations, altruism, and other interests, but undue inducement does not seem to be a significant problem based on available evidence. Payment in these studies should reflect the nature of participant confinement, anticipated discomfort from induced infection, risks and uncertainty, participant motivations, and the need to recruit from certain populations, as relevant. Where HICS involve significant risks and highly contingent social value, special review confirming the ethical permissibility of these studies can help promote confidence in the ethical permissibility of offers of payment to participate in them. We do not propose specific payment amounts for potential SARS-CoV-2 HICS, as these will be highly variable based on the relevant factors described in the report. Instead, we note that it is reasonable to start from payments offered in other similar studies, while adopting a systematic approach based on the ethical framework herein, as reflected in a pragmatic payment worksheet describing goals, coverage, factors to consider, and potential benchmarks.

Should deceased donors be allowed to donate sperm?

Deceased donor sperm donation is the subject of an article earlier this year, in light of the shortage of donated sperm in the UK:

Hodson N, Parker J. "The ethical case for non-directed postmortem sperm donation,"
Journal of Medical Ethics 2020;46:489-492.

Abstract: In this article we outline and defend the concept of voluntary non-directed postmortem sperm donation. This approach offers a potential means of increasing the quantity and heterogeneity of donor sperm. This is pertinent given the present context of a donor sperm shortage in the UK. Beyond making the case that it is technically feasible for dead men to donate their sperm for use in reproduction, we argue that this is ethically permissible. The inability to access donor sperm and the suffering this causes, we argue, justifies allowing access to sperm donated after death. Moreover, it is known that individuals and couples have desires for certain sperm donor characteristics which may not be fulfilled when numbers of sperm donors are low. Enacting these preferences contributes significantly to the well-being of intended parents, so we argue that this provides a pro tanto reason for respecting them. Finally, we explore the benefits and possible disadvantages of such a system for the various parties affected.

"The United Kingdom (UK) has a shortage of donor sperm. In 2016 there were 2273 donor insemination treatment cycles; 42% of the women registering had a male partner, 41% had a female partner and 17% were single.1 The average number of newly registered sperm donors per year between 2011 and 2013 was 586, an increase from 2004 where there were 237 donors.2 Yet this increase includes donations for specific use by a known individual to create one offspring. In 2016 the Human Fertilisation and Embryology Authority (HFEA) reported 4306 in vitro fertilisation (IVF) treatment cycles with ‘own eggs and donor sperm’ and 924 treatment cycles with ‘donor egg and donor sperm’.1 Clearly there is high demand for donor sperm and HFEA reports demonstrate this is increasing.1

"Commercial imports have been the mainstay of UK efforts to keep up with increasing demand for donor sperm.1 The Department of Health and Social Care estimates that 4000 samples were imported from the USA and 3000 from Denmark in addition to samples from other European Union (EU) countries.3 The HFEA highlights that imports are used to plug the gap because "the cost, time and resources required to recruit donors themselves is too high when there are specialist sperm banks who can carry out an efficient and reliable service".4 The Department of Health and Social Care has raised concerns that the UK's departure from the EU may worsen this state of affairs.3
...
"There are barriers to donating sperm in life that may prevent some men acting on their desire to help others or see their genes continue into future generations through donation. Posthumous sperm donation avoids most of these problems, allowing men to access the positives of sperm donation without the drawbacks. Living kidney donation provides an informative comparison between the motivations to donate in life versus after death. It is difficult to overestimate the value of donated kidneys to those individuals on the transplant list. Many people feel the pull of altruism and have a desire to help those who need a kidney transplant. Yet the potential costs of donating during life mean that individuals would rather donate after death when those costs are eliminated.16 Gamete donation after death parallels kidney donation by offering the same benefits as donation in life with fewer drawbacks, thereby both incentivising men to donate and providing greater opportunity to fulfil some of their reproductive and altruistic desires. This makes voluntary postmortem sperm donation an attractive addition to living donation.
...
"Given the potential impact of postmortem sperm donation on the family, policy decisions could be used to soften the implications of postmortem sperm donation for the family. For our purposes, the important point is that considerations of the family, including a romantic partner surviving the deceased man, do not justify a blanket ban on the use of sperm collected after death, especially if the donor has specified a desire to donate.
...
"The UK consensus is that gametes ought not to be bought although donor expenses should be covered.37 We do not take a view on this generally, but note the dissonance generated when sperm from countries such as Denmark where ‘vendors’ have been paid is used in the UK.38 In so far as society benefits from a coherent bioethical policy reflecting its shared values, using dead donors rather than donors who were paid in other countries to bolster supplies might provide a more coherent policy.

KIDNEY EXCHANGE AND THE ETHICS OF GIVING by Philippe van Basshuysen

 Philippe van Basshuysen considers various forms of kidney exchange, including non-directed (altruistic) donor chains, but not global kidney exchange (GKE), which he defers for future consideration. His work is motivated by the effective ban on kidney exchange in Germany, and, he writes, in " Bulgaria, Estonia, Finland and Hungary, among others." He also notes that non-directed donors are excluded in " Belgium, France, Greece, Poland and Switzerland..."

KIDNEY EXCHANGE AND THE ETHICS OF GIVING
Philippe van Basshuysen,  December 2019
Forthcoming in Journal of Ethics and Social Philosophy

"The arguments given here are not wedded to a specific moral theory. They will appeal to effective altruists, but because of their weak, conditional premises, many people who are not committed effective altruists will welcome them as well. They are also consistent with conservative views on donor protection and allocative justice concerning patients on waiting lists. I hope that these arguments will lead to a clarification of the debates about the ethics underlying KE programmes, particularly in countries that have hitherto banned these programmes."

Liver Paired Exchange: Ready for Prime Time in North America?

An editorial in the November 2019 Liver Transplantation considers, among other things, how liver exchange might be more coercive than live liver donation, because real or imagined incompatibilities might no longer serve to excuse an ambivalent donor from going through with the donation. (I recall discussions like this at the outset of kidney exchange, and my sense is that, in those days, the doctors thought that they could still excuse ambivalent donors by indicating that they weren't healthy enough to donate...)

Liver Paired Exchange: Ready for Prime Time in North America?
Talia B. Baker M.D

"The evolution of kidney paired exchange (KPE) in the United States has expanded transplant options for ABO‐incompatible and human leukocyte antigen–incompatible living donor pairs.1 The success of KPE has prompted consideration of liver paired exchange (LPE). Although the idea seems promising, its application has been limited to a handful of centers in Asia.2-4
...
"In the United States, approximately 3,000 patients are removed from the liver waiting list each year because they become too ill or die prior to transplant.7 Although living donor liver transplantation (LDLT) is established as the primary source of donor allografts in many parts of Asia, it constitutes approximately only 4% of liver transplants in the United States.7 The potential number of living donor and recipient pairs that might be suitable for LPE in the United States is unknown and largely unexplored.
...
"The indications for LPE are more complex than in KPE where immunological factors drive the process. In LPE, anatomical factors, such as hepatic mass (ie, graft‐to‐recipient weight ratio and percent of future liver remnant), and anatomical considerations, such as arterial and biliary variants, will also importantly be considered.
...
"coercion, which remains one of the greatest ethical concerns for the evaluation of any living donor, will have to be considered in a more robust manner. Concerns about coercion may be exacerbated by indirect exchanges, such as in LPE, because a reluctant or hesitant donor may no longer be able to invoke ABO incompatibility, size, or anatomical incompatibility as a reasonable and accepted way to withdraw from consideration as a living donor.9 ...
"Often, transplant centers are able to select the most willing donors based on their commitment to step forward, expressing unwavering interest and determination to donate. This system inherently allows willing, but ambivalent, donors to be excused based on objective medical measures (most commonly ABO incompatibility or anatomical issues) without having to admit their ambivalence. In contrast, LPE may remove or limit this potential by offering alternative options for exchanges, thereby inadvertently exposing or subjugating ambivalent donors. "

Video Interview: Peter Singer on Global Kidney Exchange

Peter Singer discusses Global Kidney Exchange, and his recent article in the Lancet, in this interview on the Practical Ethics blog at Oxford.

Video Interview: Peter Singer on The Global Kidney Exchange Programme
Published November 1, 2019 | By Katrien Devolder

"In this interview with Katrien Devolder, Peter Singer defends the Global Kidney Exchange (GKE) programme, which matches donor–recipient pairs across high-income, medium-income, and low-income countries. The GKE has been accused of being a form of organ trafficking, exploiting the poor, and involving coercion and commodification of donors. Peter Singer refutes these claims, and argues that the GKE promotes global justice and reduces the potential for people in need of kidneys in low-income and medium-income countries to be exploited."

*************

Earlier post and link to the Lancet article:

Thursday, October 31, 2019

Global Kidney Exchange in the Lancet, by Minerva, Savulescu and Singer

And you can find all my posts on global kidney exchange here.

Update: and here's the press release for the Lancet article, from Princeton's University Center for Human Values:
Peter Singer makes the case for Global Kidney Exchange Program
Thursday, Oct 31, 2019

"Professor Peter Singer is one of three bioethicists who have published an argument in The Lancet, one of the world’s leading medical journals, in favor of a Global Kidney Exchange program that matches donors and recipients across low and middle-income (LMIC) countries with pairs in high income countries.

Singer co-authored the paper  with Oxford University Professor Julian Savulescu and  Francesca Minerva, a postdoctoral fellow at the University of Ghent, in Belgium.

The three argue that, far from representing a form of organ trafficking, as some critics have suggested, a Global Kidney Exchange program would reduce suffering and save the lives of rich and poor patients alike."

Global Kidney Exchange in the Lancet, by Minerva, Savulescu and Singer

Here's a clear-eyed account of Global Kidney Exchange, from three moral philosophers, forthcoming in The Lancet. You can read the whole thing at the link:

The ethics of the Global Kidney Exchange programme
Francesca Minerva, Julian Savulescu, Peter Singer
The Lancet (online first, Published:October 29, 2019 DOI:https://doi.org/10.1016/S0140-6736(19)32474-2 )

Summary: The Global Kidney Exchange (GKE) programme seeks to facilitate kidney transplants by matching donor–recipient pairs across high-income, medium-income, and low-income countries. The GKE programme pays the medical expenses of people in medium-income and low-income countries, thus enabling them to receive a kidney transplantation they otherwise could not afford. In doing so, the programme increases the global donor pool, and so benefits people in high-income countries by improving their chances of finding a donor match. Nevertheless, the GKE has been accused of being a form of organ trafficking, exploiting the poor, and involving coercion and commodification of donors. We refute these claims, arguing that the GKE promotes global justice and reduces the potential for people in need of kidneys in low-income and medium-income countries to be exploited. Misguided objections should not be allowed to prevent the GKE from realising its potential to reduce suffering and save the lives of rich and poor patients alike.

*************
The article is very clearly written, it is well worth reading the whole thing.

In a related announcement at the University of Melbourne, Professor Singer and his colleagues have a summary (with pictures):

MAKING THE CASE FOR THE GLOBAL KIDNEY EXCHANGE
The Global Kidney Exchange, which aims to expand the kidney donor pool, has been criticised as ‘organ trafficking’, but the counter argument is that it will save the lives of rich and poor patients alike

By Professor Julian Savulescu and Professor Peter Singer, University of Melbourne, and Dr Francesca Minerva, University of Ghent

"Our paper, published in the medical journal The Lancet, provides an ethical defence of the program.

"GKE has been compared to organ selling, a practice considered immoral by many and illegal in most places. However, as nobody gets paid for giving up their kidney through the GKE programme, this comparison does not hold true"
************

Update: and here is the published version
VOLUME 394, ISSUE 10210, P1775-1778, NOVEMBER 09, 2019

A (first) liver-kidney exchange

Here's a forthcoming paper in the American Journal of Transplantation:

Bi‐organ Paired Exchange – Sentinel Case of a Liver‐Kidney Swap
by Ana‐Marie Torres  Finesse Wong  Janine Sabatte‐Caspillo  Sandy Del Grosso John P Roberts  Nancy L Ascher  Chris E Freise  Brian K Lee
First published: 12 April 2019
https://doi.org/10.1111/ajt.15386

Abstract: "Organ transplantation is the optimal treatment for patients with ESLD and ESRD. However, due to the imbalance in the demand and supply of deceased organs, most transplant centers worldwide have consciously pursued a strategy for living donation. Paired exchanges were introduced as a means to bypass various biologic incompatibilities (blood‐ and tissue‐typing), while expanding the living donor pool. This shift in paradigm has introduced new ethical concerns that have hitherto been unaddressed, especially with non‐directed, altruistic living donors. So far, transplant communities have focused efforts on separate liver‐ and kidney‐paired exchanges, whereas the concept of a trans‐organ paired exchange has been theorized and could potentially facilitate a greater number of transplants. We describe the performance of the first successful liver‐kidney swap."
******
The discussion of the ethical concerns mentioned in the abstract strike me as worth looking at, given that one of the authors, when she was president of the Transplantion Society, argued strenuously that poor patients should not be allowed to participate in American kidney exchange, for ethical reasons.

First, here are the practical steps they took:
"Our team debated the ethical underpinning of this swap. A discussion with the chair of the ethics committee at the time concluded that a full committee review was unnecessary."

Second, they considered the differential risks to the kidney and liver donors, and decided that this did not disallow the donations, since both kidney and liver donation is already accepted.

Finally they discuss the differential benefits to the liver and kidney recipients:
"Another area of contention is that donor-L’s recipient received remarkably less from a “life-enhancing” kidney transplant (rather than a truly “life-saving” liver transplant), despite the fact donor-L took on the substantially greater risk of donor hepatectomy. Our counterpoint is that the kidney recipient was spared from an extended dependency on dialysishad she stayed on the deceased donor waitlist (mortality on the kidney wait-list is 6-8% annually with a significant reduction in quality of life15,16). This does not even account for the superior allograft and patient survival outcomes that comes with a living vs. a deceased donor kidney transplant17. In fact, Merion18made the observation that the risk to patients on the kidney waitlist is not dissimilar to the liver waitlist mortality and reduction in quality of life for those with moderate MELD scores of 12-17. "

Fortunately for the patients involved, they decided that the benefits to the liver and kidney recipients were comparable. The implication is that if they had decided that the 'life-saving' benefits of a liver exceeded the 'life-enhancing' benefits of the kidney, then the exchange would have been unethical, and the ethical course of action would have been not to go ahead with it--which would likely have resulted in a quick death sentence for the liver patient, and perhaps a slower one for the kidney patient.

I'm glad that the dire decree was diverted.

It is this kind of ethical reasoning that led one of the authors to conclude that it would be unethical to go ahead with global kidney exchanges involving patient-donor pairs whose care had to be financed outside of their own countries' insurance coverage, so that, ethically, they could not be offered treatment even when financing was available. (It's lucky that the patients in this liver-kidney exchange apparently had good insurance, too.)
**********
The paper has an interesting back story in some speculative thoughts on market design.

The second reference in the paper is to a paper by computer scientists John Dickerson at Maryland and Tuomos Sandholm at CMU, proposing that multi-organ exchanges might substantially increase transplantation:
 Dickerson J, Sandholm T. Liver and multi-organ exchange. Journal of Artificial Intelligence Research. 2017;60:639

An unusual twist to the story is that it is the liver donor, eager to help her mother get a kidney transplant, who read the Dickerson-Sandholm paper and proposed the idea to the docs at UCSF.


Here's a press release from CMU, celebrating the event, and Sandholm's contributions:
Computer Science Idea Triggers First Kidney-Liver Transplant Swap
Sandholm says multi-organ exchanges could boost number of transplants

***********

Update: here's a May 11 story in the Washington Post

A daughter's gift to her mother saves two lives

Ethical algoritms: a recent talk and a forthcoming book

Increasingly, algorithms are decision makers. Here's a recent talk, and a book forthcoming in October, about what we might mean by ethical decision making by algorithms.

And here's the forthcoming book:

 The Ethical Algorithm: The Science of Socially Aware Algorithm Design Hardcover – November 1, 2019
by Michael Kearns (Author), Aaron Roth  (Author)

Ethics and Welfare Conference at Penn, Oct 26-7

" This conference will be the third in a series. The first was funded by the Becker-Friedman Institute at the University of Chicago in 2014, and the second was at the Harvard Business School.  Videos and papers from the previous conferences can be found at https://bfi.uchicago.edu/events/normative-ethics-and-welfare-economics and https://www.hbs.edu/faculty/conferences/2016-newe/Pages/schedule.aspx

"This conference is divided into seven main sessions, each devoted to a different normative question. In each session, both economic and philosophical perspectives will be presented, and ample time will be provided for audience discussion. The conference will close with a distinguished panel of economists and philosophers, who will discuss the themes raised by the conference."

Here's the program:

Friday, October 26, 2018
8:15-8:45      Breakfast

8:45-9:00      Opening Remarks

Benjamin Lockwood, University of Pennsylvania
Itai Sher, University of Massachusetts Amherst
9:00-10:30      Session 1: Ethics and Economics of Climate Change

Dale Jamieson, New York University
Christian Traeger, University of Oslo
Discussant: Arthur Van Benthem, University of Pennsylvania
10:30-11:00      Break

11:00-12:30      Session 2: Normative Uncertainty and Normative Diversity

Stefan Riedener, University of Zurich (Paper)
Itai Sher, University of Massachusetts Amherst (Paper)
Discussant: Christian Tarsney, University of Groningen
12:30-2:00      Lunch

2:00-3:30      Session 3: Preferences for Redistribution and Moral Psychology

Raymond Fisman, Boston University (Paper)
Fiery Cushman, Harvard University (Paper)
Discussant: Geoffrey Goodwin, University of Pennsylvania
3:30-4:00      Break

4:00-5:30      Session 4: Poverty, Inequality, and Health

Martin Ravallion, Georgetown University (Paper)
Jennifer Prah Ruger, University of Pennsylvania (Paper)
Discussant: Mark Pauly, University of Pennsylvania
5:30-6:30      Break

6:30-9:00      Conference Dinner (for speakers and discussants)

Saturday, October 27, 2018.
8:30-9:00      Breakfast

9:00-10:30      Session 5: Behavioral Welfare Economics and Paternalism

Benjamin Lockwood, University of Pennsylvania (Paper)
Erik Angner, Stockholm University
Discussant: Douglas Mackay, University of North Carolina at Chapel Hill
10:30-11:00      Break

11:00-12:30      Session 6: Algorithms, Data and the Public Good

Rakesh Vohra, University of Pennsylvania (Paper)
Helen Nissenbaum, Cornell University
Discussant: Daniel Singer, University of Pennsylvania
12:30-1:30      Lunch

1:30-3:00      Session 7: Happiness and Social Welfare

Kristen Cooper, Gordon College
Dan Haybron, Saint Louis University (Paper)
Discussant: Alex Rees-Jones, University of Pennsylvania
3:00-3:30      Break

3:30-5:00      Closing Panel

Ruth Chang, Rutgers University
Joel Sobel, University of California, San Diego
John Broome, University of Oxford
Steven Sheffrin, Tulane University
Moderator: Amy Sepinwall, University of Pennsylvania