Monday, March 1, 2021

Compensating challenge vaccine trial participants: further discussion in the American Journal of Bioethics

 The AJB invites commentaries on its target articles, and the comments on our article on payments in human infection challenge trials have now appeared.  (If I've done this right, you can read them by clicking on the links below.) This is from The American Journal of Bioethics, Volume 21, Issue 3 (2021)

Our target article points out that while much of the medical ethics literature focuses on the claim that payments can subject potential participants, particularly poor people, to undue influence or coercion by being too large, there can be a countervailing concern that payments that are too small can be exploitative, and that this might often be the greater ethical concern.

The commentaries are all brief, but there are nine of them, so let me recommend to my regular market design readers that two that might be rewarding to begin with are those by Julian Savulescu, and by Seán O’Neill McPartlin & Josh Morrison.

Target Article
Open Peer Commentaries
Article commentary
Pages: 32-34
Published online: 22 Feb 2021
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Article commentary
Pages: 35-37
Published online: 22 Feb 2021
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Pages: 43-45
Published online: 22 Feb 2021
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Pages: 45-47
Published online: 22 Feb 2021
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Sunday, February 28, 2021

What Motivates Paternalism? By Ambuehl, ,Bernheim and Ockenfels in the AER

 I have long been interested in repugnant transactions, which some people would like to engage in and others, not themselves involved in the transaction ('third parties') think should be forbidden.  That's a big class of phenomena (even when we exclude transactions that third parties object to because they might suffer negative externalities). In some cases (e.g. opposition to same sex marriage) there seems to be a lack of empathy with those who want or need to transact in ways that third parties object to. In other cases (e.g. opposition to surrogacy) there often seems to be a desire to protect vulnerable parties  (e.g. potential surrogate mothers) from entering into a transaction that the objecting third parties believe would harm the surrogates.  This latter kind of objection often falls under the label "paternalism."

Here's a paper in the latest AER that explores and finds paternalism in the lab.

What Motivates Paternalism? An Experimental Study By Sandro Ambuehl, B. Douglas Bernheim, and Axel Ockenfels, American Economic Review  March 2021, 111(3): 787–830, https://doi.org/10.1257/aer.20191039

Abstract: "We study experimentally when, why, and how people intervene in others' choices. Choice Architects (CAs) construct opportunity sets containing bundles of time-indexed payments for Choosers. CAs frequently prevent impatient choices despite opportunities to provide advice, believing Choosers benefit. They violate common behavioral welfare criteria by removing impatient options even when all pay-offs are delayed. CAs intervene not by removing options they wish they could resist when choosing for themselves (mistakes-projective paternalism), but rather as if they seek to align others' choices with their own aspirations (ideals-projective paternalism). Laboratory choices predict subjects' support for actual paternalistic policies. "

Saturday, February 27, 2021

Vaccine supply, and delivery, a call to increace production capacity, in Science

 The latest issue of Science has a call  by a very distinguished roster of economists, to invest in additional vaccine capacity, urgently, to shorten the time needed for the economy to fully reopen. The authors note that the savings from accelerating economic recovery are vastly larger than the costs of increasing vaccine production capacity.

Market design to accelerate COVID-19 vaccine supply  by Juan Camilo Castillo1, Amrita Ahuja2, Susan Athey3,4, Arthur Baker5, Eric Budish4,6, Tasneem Chipty7, Rachel Glennerster8, Scott Duke Kominers4,9,10, Michael Kremer4,5,*, Greg Larson11, Jean Lee12, Canice Prendergast6, Christopher M. Snyder4,13, Alex Tabarrok14, Brandon Joel Tan10, Witold Więcek

Abstract: "Build more capacity, and stretch what we already have"

Here's one among many thoughtful bits:

"Cross-country vaccine exchange

"As more vaccines are approved, given the scramble to secure bilateral deals, the nature of the fair allocation protocol adopted by COVAX (a global initiative to promote access to COVID-19 vaccines), and rapidly changing circumstances, some countries may end up with vaccine allocations that are not optimally matched to their needs. For example, some countries may have difficulty handling vaccines requiring ultracold storage or may be willing to trade off a small reduction in efficacy for a large increase in quantity. Countries allocated several vaccines may prefer to simplify logistics by consolidating on one or two.

"To facilitate efficient allocation across countries, a vaccine exchange mechanism is under consideration by COVAX. The mechanism will enable countries to engage in mutually beneficial trades of vaccine courses. Centralized market clearing will help aggregate the willingness of all countries to trade, thus maximizing gains from trade and minimizing waste of scarce vaccine courses.

"Similar mechanisms have been used successfully in other contexts where gains from trade are substantial, yet traditional cash markets are inappropriate and fairness concerns are paramount (10, 11). This setting, however, offers specific challenges. Allowable trades must satisfy regulatory approval, indemnification at the country level, and COVAX goals for population coverage. By incorporating such safeguards, an exchange can maximize efficiency, minimize waste, and ensure an equitable allocation."


Friday, February 26, 2021

Vaccine delivery improving, with congestion

 A statewide vaccine appointment list is a good idea, but it can crash:

Massachusetts Vaccination Website Crash: What Went Wrong?  The state thinks the high volume of traffic may have been the cause, but they still aren't 100% certain

"Massachusetts’ COVID-19 vaccine appointment portal temporarily crashed Thursday morning as more than 1 million additional state residents became eligible to schedule a shot.

"Gov. Charlie Baker said the administration had run through different scenarios to try to avoid problems with the vaccine portal. He said people in the administration are in the process are trying to determine what happened.

"The state on Thursday for the first time began allowing those age 65 and older, people with two or more certain medical conditions, and residents and staff of low income and affordable senior housing so sign up for a vaccine shot. But it came with a warning that it could take up to a month to book an appointment.

...

"As of Friday morning, the issues appeared to have been resolved and the website seemed to be working properly. But vaccination appointments remained hard to find.

"People who went to vaxfinder.mass.gov on Friday to book an appointment were told none were available. A statement from state health officials said “a small number of appointments for other locations,” including pharmacies and regional collaboratives, would be posted over the next few days."

Thursday, February 25, 2021

Art museums selling art: relaxing the repugnance against "deaccessioning"

 Here's an interesting look at the ways professional organizations can influence the behavior of their members by endorsing changes in social norms. In this case the association in question is the Association of Art Museum Directors.

The NY Times has the story:

Facing Deficit, Met Considers Selling Art to Help Pay the Bills. Like many museums, the Met is looking to take advantage of a relaxation of the rules governing art sales to care for collections.  By Robin Pogrebin

"Like many institutions, the Met is looking to take advantage of a two-year window in which the Association of Art Museum Directors — a professional organization that guides its members’ best practices — has relaxed the guidelines that govern how proceeds from sales of works in a collection (known as deaccessioning) can be directed.

"In the past, museums were permitted to use such funds only for future art purchases. But last spring, the association announced that, through April 10, 2022, it would not penalize museums that “use the proceeds from deaccessioned art to pay for expenses associated with the direct care of collections.”


Here's the AAMD announcement:

ASSOCIATION OF ART MUSEUM DIRECTORS’ BOARD OF TRUSTEES APPROVES RESOLUTION TO PROVIDE ADDITIONAL FINANCIAL FLEXIBILITY TO ART MUSEUMS DURING PANDEMIC CRISIS

It says in part:

"The resolutions state that AAMD will refrain from censuring or sanctioning any museum—or censuring, suspending or expelling any museum director—that decides to use restricted endowment funds, trusts, or donations for general operating expenses."


HT: Itay Fainmesser

Wednesday, February 24, 2021

A shortage of medical residency positions

 Rising numbers of American medical graduates, combined with more constant numbers of medical residencies (which are required for medical licensure), leave more graduates of international medical schools unmatched and underemployed, including many Americans who studied medicine overseas.

The NY Times has the story:

‘I Am Worth It’: Why Thousands of Doctors in America Can’t Get a Job.  Medical schools are producing more graduates, but residency programs haven’t kept up, leaving thousands of young doctors “chronically unmatched” and deep in debt.   By Emma Goldberg

"Dr. Cromblin is one of as many as 10,000 chronically unmatched doctors in the United States, people who graduated from medical school but are consistently rejected from residency programs. The National Resident Matching Program promotes its high match rate, with 94 percent of American medical students matching into residency programs last year on Match Day, which occurs annually on the third Friday in March. But the match rate for Americans who study at medical schools abroad is far lower, with just 61 percent matching into residency spots.

...

"The pool of unmatched doctors began to grow in 2006 when the Association of American Medical Colleges called on medical schools to increase their first-year enrollment by 30 percent; the group also called for an increase in federally supported residency positions, but those remained capped under the 1997 Balanced Budget Act. Senator Robert Menendez, Democrat of New Jersey, introduced the Resident Physician Shortage Reduction Act in 2019 to increase the number of Medicare-supported residency positions available for eligible medical school graduates by 3,000 per year over a period of five years, but it has not received a vote. In late December, Congress passed a legislative package creating 1,000 new Medicare-supported residency positions over the next five years."


Tuesday, February 23, 2021

A non-simultaneous liver exchange chain at UCSF, and a brief history of liver exchange

 Living donor liver transplants are relatively uncommon in North America compared to Asia.  Liver exchange might help change that. Here are some reports of recent and not so recent liver exchanges, including a non-simultaneous exchange chain  at UCSF, and a simultaneous chain in Canada.  Expect more in the near future.

 (Non-simultaneous chains have become the backbone of kidney exchange in the U.S., so we may start to see longer chains of liver exchange as well.)

Here's the most recent report of a short non-directed donor chain:

Expanding living donor liver transplantation: Report of first US living donor liver transplant chain  by Hillary J. Braun  Ana M. Torres  Finesse Louie  Sandra D. Weinberg  Sang‐Mo Kang  Nancy L. Ascher  John P. Roberts, American Journal of Transplantation, First published: 10 November 2020 https://doi.org/10.1111/ajt.16396

Abstract: "Living donor liver transplantation (LDLT) enjoys widespread use in Asia, but remains limited to a handful of centers in North America and comprises only 5% of liver transplants performed in the United States. In contrast, living donor kidney transplantation is used frequently in the United States, and has evolved to commonly include paired exchanges, particularly for ABO‐incompatible pairs. Liver paired exchange (LPE) has been utilized in Asia, and was recently reported in Canada; here we report the first LPE performed in the United States, and the first LPE to be performed on consecutive days. The LPE performed at our institution was initiated by a nondirected donor who enabled the exchange for an ABO‐incompatible pair, and the final recipient was selected from our deceased donor waitlist. The exchange was performed over the course of 2 consecutive days, and relied on the use and compliance of a bridge donor. Here, we show that LPE is feasible at centers with significant LDLT experience and affords an opportunity to expand LDLT in cases of ABO incompatibility or when nondirected donors arise. To our knowledge, this represents the first exchange of its kind in the United States."

The paper says this about the timing of the surgeries:

"Other centers reporting LPE have performed the donor and recipient operations in four operating rooms simultaneously4, 5 which can be logistically challenging, but addresses concerns regarding simultaneity and equalizing risk. In our case, we performed the operations on sequential days. In doing so, we accepted the risk that, given a good outcome in Recipient 1 on the first day, Donor 2 (the “bridge” donor) might opt out of living donation at the last moment. Reappropriating terminology from the kidney paired exchange (KPE) literature, a bridge donor is defined as someone who donates more than 1 day after their intended recipient received a transplant.12 A recent paper discussing the feasibility of LPE in the United States emphasized that, in the early days of KPE, there was concern that the bridge donor might back out at the last minute and break the chain.13 As a result, kidney donor operations were initially attempted simultaneously. However, a 2018 review of 344 KPE chains between 2008 and 2016 revealed that only 5.6% of bridge donors broke the chain and the majority of these donors developed a medical issue during their time as a bridge donor that prohibited them from completing donation.12 Ultimately, because this occurrence was so infrequent, the authors concluded that simultaneous donor operating rooms for chains are unnecessary and may actually deter potential donors based on logistical issues. "

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And here's a report from Canada of a non-directed donor chain of liver exchange with all surgeries conducted simultaneously (also with the NDD donating to an incompatible patient-donor pair whose donor donated to a patient on the deceased donor waiting list).

Living donor liver paired exchange: A North American first  by Madhukar S. Patel  Zubaida Mohamed  Anand Ghanekar  Gonzalo Sapisochin  Ian McGilvray  Blayne A. Sayed  Trevor Reichman  Markus Selzner  Jed A. Gross  Zita Galvin  Mamatha Bhat  Les Lilly  Mark Cattral  Nazia Selzner, American Journal of Transplantation, First published: 10 June 2020 https://doi.org/10.1111/ajt.16137 

Abstract: Paired organ exchange can be used to circumvent living donor‐recipient ABO incompatibilities. Herein, we present the first case of successful liver paired exchange in North America. This 2‐way swap required 4 simultaneous operations: 2 living donor hepatectomies and 2 living donor liver transplants. A nondirected anonymous living donor gift initiated this domino exchange, alleviating an ABO incompatibility in the other donor‐recipient pair. With careful attention to ethical and logistical issues, paired liver exchange is a feasible option to expand the donor pool for incompatible living liver donor‐recipient pairs.

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Here's a 2014 report from S. Korea:

Section 16. Update on Experience in Paired-Exchange Donors in Living Donor Liver Transplantation For Adult Patients at ASAN Medical Center by  Jung, Dong-Hwan1; Hwang, Shin1; Ahn, Chul-Soo1; Kim, Ki-Hun1; Moon, Deok-Bog1; Ha, Tae-Yong1; Song, Gi-Won1; Park, Gil-Chun1; Lee, Sung-Gyu, Transplantation: April 27, 2014 - Volume 97 - Issue - p S66-S69, doi: 10.1097/01.tp.0000446280.81922.bb

"Between January 2003 and December 2011, approximately 2,182 adult LDLT cases were included in this study. During this period, 26 paired-exchange donor LDLT cases were performed (1.2%).

"Results: Of the 26 paired-exchange donor LDLT cases, 22 pairs were matched due to ABO-incompatibility, and 4 pairs were matched because of cascade allocation of unrelated donors or relatively small graft volume to the recipients. A total of 28 living donors were included in the 26 paired-exchange donor LDLT cases because of inclusion of two dual-graft transplants. Elective surgery was performed in 22 cases, and urgent operation was performed in 4 cases. The overall 1-year and 5-year patient and graft survivals were both 96.2% and 90.1%, respectively.

"Conclusions : Our experience suggests that the paired-exchange donor program for adult LDLT seems to be a feasible modality to overcome donor ABO incompatibility."

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Here's a story of a liver exchange in Texas, between an incompatible pair and a compatible pair.

Saturday, December 28, 2019 A liver exchange in San Antonio, Texas

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Here's a liver exchange in Hong Kong between an incompatible pair and a compatible pair.

Friday, April 4, 2014 An unusual liver exchange in Hong Kong

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Here's a report from two major liver transplant centers in Hong Kong and S. Korea. The Korean team reported 16 donor exchanges conducted over a 6-year period.

Friday, April 9, 2010 Liver exchange



Monday, February 22, 2021

Ethical Payment in Human Infection Challenge Studies in the American Journal of Bioethics

 There are likely more vaccine trials ahead of us, of new vaccines and modifications of old ones to defend against new variants of covid. Here's a just-published paper, written when vaccine trials were still in the future. It's still relevant, because challenge trials (in which volunteers are exposed to a particular virus) can be much more focused than ordinary vaccine trials (particularly as the prevalence of disease begins to decline...see yesterday's post).

Promoting Ethical Payment in Human Infection Challenge Studies

Holly Fernandez Lynch, Thomas C. Darton, Jae Levy, Frank McCormick, Ubaka Ogbogu, Ruth O. Payne, Alvin E. Roth, Akilah Jefferson Shah, Thomas Smiley and Emily A. Largent            

Published online: 04 Feb 2021, The American Journal of Bioethics,  https://doi.org/10.1080/15265161.2020.1854368

Abstract: To prepare for potential human infection challenge studies (HICS) involving SARS-CoV-2, we convened a multidisciplinary working group to address ethical questions regarding whether and how much SARS-CoV-2 HICS participants should be paid. Because the goals of paying HICS participants, as well as the relevant ethical concerns, are the same as those arising for other types of clinical research, the same basic framework for ethical payment can apply. This framework divides payment into reimbursement, compensation, and incentives, focusing on fairness and promoting adequate recruitment and retention as counterweights to concerns about undue inducement. Within the basic framework, several factors are especially salient for HICS, and for SARS-CoV-2 HICS in particular, including the nature of participant confinement, anticipated discomfort, risks and uncertainty, participant motivations, and trust. These factors are reflected in a payment worksheet created to help sponsors, researchers, and ethics reviewers systematically develop and assess ethically justifiable payment amounts.


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Here's a link to the original (long) working paper:

Wednesday, August 19, 2020

Sunday, February 21, 2021

Human infection challenge trials for Covid vaccine to move forward in UK

 The BBC has this story:

Covid-19: World's first human trials given green light in UK

"Healthy, young volunteers will be infected with coronavirus to test vaccines and treatments in the world's first Covid-19 "human challenge" study, which will take place in the UK.

"The study, which has received ethics approval, will start in the next few weeks and recruit 90 people aged 18-30.

"They will be exposed to the virus in a safe and controlled environment while medics monitor their health.

...

"The Human Challenge study is being delivered by a partnership between the UK government's Vaccines Taskforce, Imperial College London, the Royal Free London NHS Foundation Trust and the company hVIVO, which has pioneered viral human challenge models.Clive Dix, interim chair of the Vaccines Taskforce, said: "We have secured a number of safe and effective vaccines for the UK, but it is essential that we continue to develop new vaccines and treatments for Covid-19.

"We expect these studies to offer unique insights into how the virus works and help us understand which promising vaccines offer the best chance of preventing the infection."

...

"Initially, the study will use the virus that has been circulating in the UK since the pandemic began in March, which is of low risk to healthy adults, to deliberately infect volunteers.

"In time, a small numbers of volunteers are likely to be given an approved vaccine and then exposed to the new variants, helping scientists to find out the most effective jabs - but this phase of the study has not yet been given the go-ahead."


HT: Tom Darton

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And here's a story from the NY Times, which touches on the issue of compensation for participants (and the associated debate about whether that is repugnant):

U.K. Approves Study That Will Deliberately Infect Volunteers With Coronavirus. Researchers hope to learn things about how the immune system responds to the coronavirus that would be impossible outside a lab.  By Benjamin Mueller

"After being exposed to the virus, the participants will be isolated for two weeks in the hospital. For that and the year’s worth of follow-up appointments that are planned, they will be paid 4,500 pounds, or about $6,200. The researchers said that would compensate people for time away from jobs or families without creating too large an economic incentive for people to participate."

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Related posts on challenge trials:   https://marketdesigner.blogspot.com/search/label/challenge

Saturday, February 20, 2021

Canadian organ donations down sharply during pandemic

 During the pandemic, Canadian kidney exchange was suspended, and organ donation was sharply reduced.

The ChronicleHerald has the story:

Organ donations down sharply during pandemic  by Andrew Duffy

"Organ donations in Canada have dropped significantly during the pandemic even though COVID-19 has raised the country’s annual death toll.

"Medical officials say organ donations are down 20 to 30 per cent from pre-pandemic levels.

...

"Living donations, including kidney and liver donations, are down 30 per cent, Shemie said, while organ donations from deceased patients have dropped 21 per cent.

"There are a variety of reasons for those declines, he said, starting with the impact of the pandemic on intensive care units (ICUs). Organ donors are identified and managed in ICUs, but those units have been swamped with COVID-19 cases at various times during the past 10 months, he said. Transplant recipients also need to spend time in ICUs recovering from their surgeries.

...

"What’s more, he said, the pandemic has reduced the pool of potential organ donors because the number of people suffering devastating brain injuries has gone down. Lockdown restrictions mean fewer people are driving cars or playing sports with a resultant drop in serious injuries.

...

"More than 20,000 Canadians have died from COVID-19 during the past year, but the disease makes them unsuitable as organ donors. “There are a substantial number of people who are dying, tragically, of COVID, but because they have COVID, they can’t become donors,” Shemie said.

...

"In Italy, transplant doctors have made limited use of donated organs from COVID-19 patients. In that country, people on the transplant wait list who have survived COVID-19 are eligible to receive organs donated by people who have died with the disease, Shemie said.

...

"Canadian Blood Services recently announced that its Kidney Paired Donation program, an inter-provincial organ sharing effort, is back up and running after a temporary pause. "

Friday, February 19, 2021

The 1% Steps for Health Care Reform Project (including kidney exchange)

 The goal of the 1% Steps for Health Care Reform Project is to shift the way we think about health care spending in the US and offer a roadmap to policy makers of tangible steps we as a country can take to lower the cost of health care in the US. We want to leverage leading scholars’ work to identify discrete problems in the US health system and offer evidence-based steps for reform. We will continually update the project with new proposals that are based on the latest academic research.

Here is their full list of Policy Briefs.

Here's one on kidney exchange:

Expanding Kidney Exchange

Authors: Nikhil Agarwal, Massachusetts Institute of Technology; Itai Ashlagi, Stanford University; Michael Rees, The University of Toledo Medical Center; Alvin Roth, Stanford University

Here's one paragraph:

"Policy Proposal: This brief discusses three specific proposals for expanding kidney exchange. First, policy makers should eliminate financial disincentives for participating in kidney exchange platforms by including medical and administrative costs specific to kidney exchange in reimbursements from the Medicare program. Second, policy makers should direct the federal contractor UNOS (United Network for Organ Sharing) to allow kidney exchange chains to be initiated by deceased donors. Third, Medicare should pay for the costs of a global kidney exchange that allows exchanges involving patients in different nations."

And here's some discussion by Nikhil Agarwal with Zack Cooper: