Showing posts sorted by relevance for query convalescent. Sort by date Show all posts
Showing posts sorted by relevance for query convalescent. Sort by date Show all posts

Monday, December 4, 2023

Convalescent plasma: the picture is getting clearer

 Slowly, there is evidence accumulating that convalescent plasma is helpful in treating patients with severe Covid, if it is administered early.  There is also evidence that it doesn't help much once the disease has become well established, particularly when the primary symptoms become due to the body's own immune reaction.  These caveats help explain why early reports did not find an effect of convalescent plasma--i.e. it helped only a subset of the patients to whom it was administered. But for those it was sometimes life saving. Here is a recent paper from the New England Journal of Medicine.

Convalescent Plasma for Covid-19–Induced ARDS in Mechanically Ventilated Patients by Benoît Misset, M.D., Michael Piagnerelli, M.D., Ph.D., Eric Hoste, M.D., Ph.D., Nadia Dardenne, M.Sc., David Grimaldi, M.D., Ph.D., Isabelle Michaux, M.D., Ph.D., Elisabeth De Waele, M.D., Ph.D., Alexander Dumoulin, M.D., Philippe G. Jorens, M.D., Ph.D., Emmanuel van der Hauwaert, M.D., Frédéric Vallot, M.D., Stoffel Lamote, M.D., et al., October 26, 2023, N Engl J Med 2023; 389:1590-1600 DOI: 10.1056/NEJMoa2209502

"Abstract

BACKGROUND

Passive immunization with plasma collected from convalescent patients has been regularly used to treat coronavirus disease 2019 (Covid-19). Minimal data are available regarding the use of convalescent plasma in patients with Covid-19–induced acute respiratory distress syndrome (ARDS).

METHODS

In this open-label trial, we randomly assigned adult patients with Covid-19–induced ARDS who had been receiving invasive mechanical ventilation for less than 5 days in a 1:1 ratio to receive either convalescent plasma with a neutralizing antibody titer of at least 1:320 or standard care alone. Randomization was stratified according to the time from tracheal intubation to inclusion. The primary outcome was death by day 28.

RESULTS

A total of 475 patients underwent randomization from September 2020 through March 2022. Overall, 237 patients were assigned to receive convalescent plasma and 238 to receive standard care. Owing to a shortage of convalescent plasma, a neutralizing antibody titer of 1:160 was administered to 17.7% of the patients in the convalescent-plasma group. Glucocorticoids were administered to 466 patients (98.1%). At day 28, mortality was 35.4% in the convalescent-plasma group and 45.0% in the standard-care group (P=0.03). In a prespecified analysis, this effect was observed mainly in patients who underwent randomization 48 hours or less after the initiation of invasive mechanical ventilation. Serious adverse events did not differ substantially between the two groups.

CONCLUSIONS

The administration of plasma collected from convalescent donors with a neutralizing antibody titer of at least 1:160 to patients with Covid-19–induced ARDS within 5 days after the initiation of invasive mechanical ventilation significantly reduced mortality at day 28. This effect was mainly observed in patients who underwent randomization 48 hours or less after ventilation initiation."

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Here are my posts on convalescent plasma, and the confusing initial reports about its effects.

Wednesday, May 20, 2020

Convalescent plasma collection and distribution

Efforts to collect and distribute convalescent plasma from recovered Covid-19 patients are ramping up: there are lots of options.


I donate convalescent plasma at the Stanford Blood Center, in their program on
 CONVALESCENT PLASMA FROM RECOVERED COVID-19 PATIENTS
"This exciting initiative involves taking plasma donations from recovered COVID-19 patients and transfusing that plasma into critically ill COVID-19 patients in the hopes that the antibodies present in the donated plasma will help save the lives of the recipients."

Modern plasma collection is a one-arm process: the machine on my right in the photo alternates between taking blood and returning red blood cells through the same needle (in contrast to the old technology which had blood go out of a needle in one arm and red blood cells return through a needle in the other arm).

Collecting convalescent plasma is not regulated as a research activity, it is just ordinary plasma donation. However giving it to patients is done under FDA guidance, either as a research activity or as an emergency intervention for very ill patients:
Recommendations for Investigational COVID-19 Convalescent Plasma
"Because COVID-19 convalescent plasma has not yet been approved for use by FDA, it is regulated as an investigational product."

There are three FDA-approved pathways right now by which convalescent plasma can be administered to patients.
"Pathways for Use of Investigational COVID-19 Convalescent Plasma:
1. Clinical Trials,
2.  Expanded Access "for patients with serious or immediately life-threatening COVID-19 disease"
3. Single Patient Emergency"

Here is a consortium of nonprofit blood centers, there's likely one near you if you're reading this in the States:
America's Blood Centers (association of independent blood centers)
Here's the American Red Cross effort: Plasma Donations from Recovered COVID-19 Patients

My impression is that the nonprofit blood centers don't pay donors, but are able to sell plasma to customers, including the commercial plasma industry, as part of the thriving domestic and international market in plasma. (I blogged Monday about U.S. plasma exports, all over the world, including especially countries in which compensating donors is repugnant.)
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The for-profit plasma industry (which compensates plasma donors) is represented by The Plasma Protein Therapeutics Association (PPTA)
Here's an announcement about their plans for Covid-19 antibodies:
  1. CoVIg-19 Plasma Alliance Builds Strong Momentum Through Expanded Membership and Clinical Trial Collaboration
"The CoVIg-19 Plasma Alliance, an unprecedented plasma industry collaboration recently established to accelerate the development of a plasma-derived hyperimmune globulin therapy for COVID-19, is rapidly building momentum. Its membership has expanded globally to include 10 plasma companies, and now also includes global organizations from outside the plasma industry who are providing vital support to encourage more people to donate plasma.

"In addition to those announced at its inception - Biotest, BPL, CSL Behring, LFB, Octapharma and Takeda - the Alliance welcomes new industry members ADMA Biologics, BioPharma Plasma, GC Pharma, and Sanquin. Together, these organizations will contribute specialist advisory expertise, technical guidance and/or in-kind support to contribute to the Alliance goal of accelerating development and distribution of a potential treatment option for COVID-19."
*******

"In Minnesota, a program coordinated by the Mayo Clinic has collected plasma from more than 12,000 COVID survivors for transfusion into more than 7,000 gravely ill patients, the result of a massive public appeal led by government leaders and nonprofit groups such as the Red Cross.

"Meanwhile, for-profit companies that typically pay $50 per donation of plasma used in other lifesaving therapies are advertising aggressively — and significantly bumping up their rates for COVID donors.

"In Utah, John and Melanie Haering, who contracted COVID-19 aboard the ill-fated Diamond Princess cruise ship, received gift cards worth $800 after making two donations apiece at a Takeda Pharmaceuticals' BioLife Plasma Services center. BioLife runs several of the more than 800 paid-plasma collection sites in the U.S., part of an industry that produces plasma protein therapies used to treat rare, chronic conditions such as hemophilia and in medical emergencies."

Saturday, November 28, 2020

Convalescent plasma for Covid-19 may not be as effective as hoped

 Here's a recent article from the New England Journal of Medicine: they conclude that treatment of Covid-19 patients with convalescent plasma is no better than a placebo treatment (for a group of seriously ill patients with over a 10% mortality rate).


A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia

by Ventura A. Simonovich, M.D., Leandro D. Burgos Pratx, M.D., Paula Scibona, M.D., María V. Beruto, M.D., Marcelo G. Vallone, M.D., Carolina Vázquez, M.D., Nadia Savoy, M.D., Diego H. Giunta, M.D., M.P.H., Ph.D., Lucía G. Pérez, M.D., Marisa del L. Sánchez, M.D., Andrea Vanesa Gamarnik, Ph.D., Diego S. Ojeda, Ph.D., et al., for the PlasmAr Study Group

RESULTS: A total of 228 patients were assigned to receive convalescent plasma and 105 to receive placebo. The median time from the onset of symptoms to enrollment in the trial was 8 days (interquartile range, 5 to 10), and hypoxemia was the most frequent severity criterion for enrollment. The infused convalescent plasma had a median titer of 1:3200 of total SARS-CoV-2 antibodies (interquartile range, 1:800 to 1:3200]. No patients were lost to follow-up. At day 30 day, no significant difference was noted between the convalescent plasma group and the placebo group in the distribution of clinical outcomes according to the ordinal scale (odds ratio, 0.83 (95% confidence interval [CI], 0.52 to 1.35; P=0.46). Overall mortality was 10.96% in the convalescent plasma group and 11.43% in the placebo group, for a risk difference of −0.46 percentage points (95% CI, −7.8 to 6.8). Total SARS-CoV-2 antibody titers tended to be higher in the convalescent plasma group at day 2 after the intervention. Adverse events and serious adverse events were similar in the two groups.


CONCLUSIONS: No significant differences were observed in clinical status or overall mortality between patients treated with convalescent plasma and those who received placebo. 


HT: Irene Wapnir

Sunday, May 17, 2020

Cascades of convalescent plasma for Covid-19, and chains of exchanges, by Kominers, Pathak, Sönmez, and Ünver

Covid-19 convalescent plasma is a new thing in the world, that came into existence only when the first human was infected and recovered from the Covid-19 disease that is now pandemic. It isn't clear yet whether it will be clinically valuable, but recovered antibodies have been valuable for some other diseases, so there's excellent reason to hope that will be the case now too.  And as the number of people grows who have recovered from Covid-19, it is likely that the supply of antibodies is growing much faster, since antibody-containing plasma can be donated once a month or so. (There are  ongoing studies of antibody production by recovered patients, examining how long the antibodies remain at high levels, post-recovery). Of course, most of that supply is sequestered in the blood of recovered patients, so there's a non-trivial issue of collection and distribution.

As readers of this blog know, many countries prohibit the sale of plasma. Will Americans continue to support a commercial market for Covid-19 convalescent plasma in the current pandemic?  A distinguished group of market designers has written a paper considering how to apply techniques developed for kidney exchange to the task of collecting convalescent plasma from recovered Covid-19 patients, if it becomes impossible to buy and sell it. In particular, they consider how to create chains of donations, without using money, to overcome the shortages they anticipate.

Here's an easy to read account by Scott Kominers, one of the authors.

Scott Duke Kominers, Bloomberg News  May 11, 2020

"convalescent plasma is in short supply: although it’s hard to estimate precisely, some statistics suggest the U.S. may need twice as much as we have on hand.

"In a new paper, Parag A. Pathak, Tayfun Sonmez, M. Utku Unver and I propose a market design strategy that could help close the gap. Our approach makes use of two special features of the way plasma donation works.

"First, convalescent plasma is collected from recently recovered patients, which means that today’s patients become tomorrow’s prospective donors, assuming they manage to beat the virus. ... That suggests the shortage isn’t from lack of potential supply.

"Second, plasma donation is more than one-for-one: the typical donor can give enough plasma at one time for multiple treatments, and they can potentially donate more than once. As a result, assuming plasma therapy does help patients recover, there is a so-called flywheel effect: the more we use the treatment, the more plasma is available -- provided enough recovered patients are willing to donate.

"Many people would like to donate plasma to help a loved one, but can’t for various reasons:  Their blood types might be incompatible or they might live far away and be unable to travel. To address these sorts of obstacles, my collaborators and I suggest that each plasma donor could receive a voucher that can be used to give a family member or friend priority for plasma treatment. Because donation is more than one-for-one, it’s possible to honor vouchers while still increasing the pool of plasma available to treat other patients.
...
"A similar analysis suggests a role for a pay-it-forward system, where we make a point of treating patients who pledge to donate plasma, assuming they recover and are medically able to do so. Because recovered patients can typically donate more plasma than was needed for their own treatment, this again can help increase the plasma supply in the long run. As a result, my collaborators and I show that, somewhat paradoxically, prioritizing patients who pledge to donate can still end up expanding treatment for the patients who are unable to pledge, or just choose not to.

"Both of these policies are similar to systems we’ve used to expand kidney donation in the U.S.: Priority vouchers are sometimes granted when a living donor gives a kidney to a third-party before one of their family members needs a transplant. And pay-it-forward incentives are used in kidney exchange chains, where a patient with a medically incompatible prospective donor receives a kidney from a third-party donor, and then their donor later gives a kidney to some other patient."
******
Here is the paper itself:

Paying It Backward and Forward: Expanding Access to Convalescent Plasma Therapy Through Market Design
Scott Duke Kominers, Parag A. Pathak, Tayfun Sönmez, M. Utku Ünver
NBER Working Paper No. 27143
Issued in May 2020

Abstract: COVID-19 convalescent plasma (CCP) therapy is currently a leading treatment for COVID19. At present, there is a shortage of CCP relative to demand. We develop and analyze a model of centralized CCP allocation that incorporates both donation and distribution. In order to increase CCP supply, we introduce a mechanism that utilizes two incentive schemes, respectively based on principles of “paying it backward” and “paying it forward.” Under the first scheme, CCP donors obtain treatment vouchers that can be transferred to patients of their choosing. Under the latter scheme, patients obtain priority for CCP therapy in exchange for a future pledge to donate CCP if possible. We show that in steady-state, both principles generally increase overall treatment rates for all patients—not just those who are voucher-prioritized or pledged to donate. Our results also hold under certain conditions if a fraction of CCP is reserved for patients who participate in clinical trials. Finally, we examine the implications of pooling blood types on the efficiency and equity of CCP distribution.

Here's some of the motivation for their model:
"There is an active debate in economics and philosophy on the appropriate role of market-based
mechanisms with compensation for human products used in medicine or medical research like kidneys, blood, blood products, sperm, breast milk, bone marrow, and other.11 Since, as far as we know, there is no current market where infected patients can buy CCP or where recovered patients can sell CCP, we do not consider this possibility as part of our model.
...
"Because CCP is a form of plasma, a natural question is whether a compensated market for CCP will develop. In our model, there is no option to pay to receive CCP or be paid for donating CCP, but a donor can designate the voucher in our model to particular patient in need. As a result, our model of CCP falls between the two extremes described above. We expect that in a crisis moment, there is unlikely to be an active compensated market for CCP (even though it may be impossible to fully prohibit resale of vouchers). If a price-based market does develop, society may deem it unacceptable."
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I am more optimistic than they are about the likely available supply of convalescent plasma if it proves useful, through existing commercial channels. My optimism is based on the large thriving commercial market for plasma and plasma-derived antibodies in the U.S., and around the world.  I'll try to blog about the general plasma and antibody (immunoglobulin) market tomorrow, and perhaps more on Covid-19 antibodies later this week.

Monday, June 6, 2022

The return of convalescent plasma as a treatment for Covid

 As evidence accumulates, it appears that convalescent plasma helps some patients with Covid.  Here's an article from Medpage

COVID Convalescent Plasma Finds a Therapeutic Role. — Growing evidence shows benefits in the immunocompromised

by Arturo Casadevall, MD, PhD, Jeffrey P. Henderson MD, PhD, Brenda J. Grossman, MD, MPH, Michael J. Joyner, MD, Shmuel Shoham, MD, Nigel Paneth, MD, MPH, and Liise-anne Pirofski, MD June 19, 2022

"In the dark days of the early COVID-19 pandemic, when there was no known therapy, COVID-19 convalescent plasma (CCP) brought a ray of hope. COVID-19 survivors, community organizers, clinicians, regulators, and blood bankers collaborated to quickly bring CCP to patients. First used at the end of March 2020 in the U.S., 40% of all hospitalized patients were being treated with CCP by October 2020, considerable progress for a treatment without pharmaceutical industry support.

"Since those early days, CCP use has largely fallen off based on insufficient evidence of efficacy in hospitalized patients and the availability of other therapies. But growing evidence has shown benefits of CCP in a population with diminished treatment options and vaccine responses: the immunocompromised. This population encompasses about 3% of the population and their needs have been relatively neglected in treatment guidelines during the COVID-19 pandemic.

...

"As the pandemic progressed, further evidence showing that CCP was effective when used early and with high antibody content emerged, strengthening support for the FDA EUA in specific groups. However, with evidence of widespread benefit being considered insufficient in the broader patient population, CCP was largely branded as ineffective, collections dropped, and little or no CCP was available when Omicron surged in early 2022.

...

"The continued needs of immunocompromised patients and the discovery that CCP obtained from vaccinated convalescent donors possess extremely high levels of antibodies that neutralize all known variants to date, including Omicron, have promoted a CCP comeback. CCP use is now recommended for immunocompromised patients by multiple major professional organizations, including the Infectious Diseases Society of America (IDSA) and the Association for the Advancement of Blood and Biotherapies (AABB).

*********

Earlier:

Sunday, April 25, 2021

Saturday, August 8, 2020

Is convalescent plasma useful for treating covid-19?

The reported results on convalescent plasma are so far still quite incomplete, and mixed.  If I had to summarize, I'd say that a growing body of evidence suggests that treating early stage (e.g. just hospitalized) covid-19 patients increases and speeds the chance of recovery, while there is little convincing evidence that convalescent plasma helps more severely ill patients who have begun to have serious complications.

Here is a recent WSJ article:

By Amy Dockser Marcus

"Hospitalized Covid-19 patients who received transfusions of blood plasma rich with antibodies from recovered patients reduced their mortality rate by about 50%, according to researchers running a large national study.
...
"The researchers said they saw signs that the treatment might be working in patients who received high levels of antibodies in plasma early in the course of their illness. They based their conclusions on an analysis of about 3,000 patients."
************

Here's a recent paper in JAMA on a very small randomized trial in China that doesn't find statistically significant effects on patients who 

August 4, 2020
Ling Li, MD, PhD; Wei Zhang, MD; Yu Hu, MD, PhD; Xunliang Tong, MD, PhD; Shangen Zheng, MD; Juntao Yang, PhD; Yujie Kong, MD; Lili Ren, PhD; Qing Wei, MD; Heng Mei, MD, PhD; Caiying Hu, MD; Cuihua Tao, MD; Ru Yang, MD; Jue Wang, MD; Yongpei Yu, PhD; Yong Guo, PhD; Xiaoxiong Wu, MD; Zhihua Xu, MD; Li Zeng, MD; Nian Xiong, MD, PhD; Lifeng Chen, MD; Juan Wang, MD; Ning Man, MD; Yu Liu, PhD; Haixia Xu, MD; E. Deng, MS; Xuejun Zhang, MS; Chenyue Li, MD; Conghui Wang, PhD; Shisheng Su, PhD; Linqi Zhang, PhD; Jianwei Wang, PhD; Yanyun Wu, MD, PhD; Zhong Liu, MD, PhD
  JAMA. 2020; 324(5):460-470. doi: 10.1001/jama.2020.10044

Abstract: This randomized trial compares the effects of convalescent plasma therapy with standard care vs standard care alone on time to clinical improvement among patients with severe or life-threatening COVID-19 disease in China.

"Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment did not significantly improve the time to clinical improvement within 28 days, although the trial was terminated early and may have been underpowered to detect a clinically important difference."
**********

My last donation had high enough antibodies to qualify me for another: I hope these are going to patients for whom they will be useful.

Friday, January 15, 2021

More on convalescent plasma for treating Covid-19

Early results concerning the effectiveness of convalescent plasma have been mixed.  Here's a new study, in the NEJM, and reported in the NY Times. (see my earlier posts here.)

Here's the Times story:

Blood Plasma Reduces Risk of Severe Covid-19 if Given Early  By Katherine J. Wu

"A small but rigorous clinical trial in Argentina has found that blood plasma from recovered Covid-19 patients can keep older adults from getting seriously sick with the coronavirus — if they get the therapy within days of the onset of the illness.

"The results, published Wednesday in the New England Journal of Medicine, are some of the first to conclusively point toward the oft-discussed treatment’s beneficial effects."


And here's the NEJM article:

Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults

List of authors.

Romina Libster, M.D., Gonzalo Pérez Marc, M.D., Diego Wappner, M.D., Silvina Coviello, M.S., Alejandra Bianchi, Virginia Braem, Ignacio Esteban, M.D., Mauricio T. Caballero, M.D., Cristian Wood, M.D., Mabel Berrueta, M.D., Aníbal Rondan, M.D., Gabriela Lescano, M.D., et al., for the Fundación INFANT–COVID-19 Group*

"BACKGROUND: Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness.

METHODS: We conducted a randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adult patients within 72 hours after the onset of mild Covid-19 symptoms. The primary end point was severe respiratory disease, defined as a respiratory rate of 30 breaths per minute or more, an oxygen saturation of less than 93% while the patient was breathing ambient air, or both. The trial was stopped early at 76% of its projected sample size because cases of Covid-19 in the trial region decreased considerably and steady enrollment of trial patients became virtually impossible.

RESULTS: A total of 160 patients underwent randomization. In the intention-to-treat population, severe respiratory disease developed in 13 of 80 patients (16%) who received convalescent plasma and 25 of 80 patients (31%) who received placebo (relative risk, 0.52; 95% confidence interval [CI], 0.29 to 0.94; P=0.03), with a relative risk reduction of 48%. A modified intention-to-treat analysis that excluded 6 patients who had a primary end-point event before infusion of convalescent plasma or placebo showed a larger effect size (relative risk, 0.40; 95% CI, 0.20 to 0.81). No solicited adverse events were observed.

CONCLUSIONS: Early administration of high-titer convalescent plasma against SARS-CoV-2 to mildly ill infected older adults reduced the progression of Covid-19. "

Wednesday, April 8, 2020

Plasma donation, "convalescent plasma" and Covid-19 antibodies

Blood plasma is a big source of antibodies for people who don't make their own, and in these days of Covid-19 pandemic, antibodies are again in the news. As the number of recovering patients grows, can the antibodies they produce be of help in stemming the spread of the disease, or in curbing its intensity?

Here's a just published report of a quite preliminary study from China, in the PNAS:

Effectiveness of convalescent plasma therapy in severe COVID-19 patients
by Kai Duan, ... Xiaoming Yang (46 authors)
PNAS first published April 6, 2020 https://doi.org/10.1073/pnas.2004168117
Contributed by Zhu Chen, March 18, 2020 (sent for review March 5, 2020; reviewed by W. Ian Lipkin and Fusheng Wang)


"Significance: COVID-19 is currently a big threat to global health. However, no specific antiviral agents are available for its treatment. In this work, we explore the feasibility of convalescent plasma (CP) transfusion to rescue severe patients. The results from 10 severe adult cases showed that one dose (200 mL) of CP was well tolerated and could significantly increase or maintain the neutralizing antibodies at a high level, leading to disappearance of viremia in 7 d. Meanwhile, clinical symptoms and paraclinical criteria rapidly improved within 3 d. Radiological examination showed varying degrees of absorption of lung lesions within 7 d. These results indicate that CP can serve as a promising rescue option for severe COVID-19, while the randomized trial is warranted."
**********

Here's a story from the WSJ:

Coronavirus Survivors Keep Up the Fight, Donate Blood Plasma to Others
National Covid-19 project seeks volunteers to aid the seriously ill; ‘I feel obligated to help’
By Amy Dockser Marcus

"The Mount Sinai Hospital in New York, where Mr. Sherman volunteered to donate plasma, is one of 34 institutions around the country participating in the National Covid-19 Convalescent Plasma Project, which is seeking blood-plasma donations from recovered patients who have a confirmed Covid-positive test and are at least 21 days out from the onset of symptoms.
...
“The biggest problem is not the lack of donors,” said Arturo Casadevall, a professor at the Johns Hopkins Bloomberg School of Public Health, in Baltimore, and one of the organizers of the national project. “It is the logistics of figuring out how people who want to participate can actually donate.”

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And here's a plasma industry press release:

Global Plasma Leaders Collaborate to Accelerate Development of Potential COVID-19 Hyperimmune Therapy

"Osaka, JAPAN, and King of Prussia, PA, USA – April 6, 2020 –  Biotest, BPL, LFB, and Octapharma have joined an alliance formed by CSL Behring (ASX:CSL/USOTC:CSLLY) and Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) to develop a potential plasma-derived therapy for treating COVID-19. The alliance will begin immediately with the investigational development of one, unbranded anti-SARS-CoV-2 polyclonal hyperimmune immunoglobulin medicine with the potential to treat individuals with serious complications from COVID-19.
...
"Developing a hyperimmune will require plasma donation from many individuals who have fully recovered from COVID-19, and whose blood contains antibodies that can fight the novel coronavirus. Once collected, the “convalescent” plasma would then be transported to manufacturing facilities where it undergoes proprietary processing, including effective virus inactivation and removal processes, and then is purified into the product."

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My other posts on plasma, mostly focused on repugnance to compensation for donors. Here's one that explains some of the underlying medical issues:

Thursday, July 11, 2019

Monday, March 6, 2023

Reconsideration of covid convalescent plasma

Recently Statnews reported that Covid convalescent plasma (CCP) may in fact be useful in preventing severe illness, despite the fact that earlier clinical trials did not show success in reversing severe illness:

Covid convalescent plasma: the ‘little engine that could’  By Michael J. Joyner, Nigel Paneth and Arturo Casadevall

"Unlike monoclonal antibodies, which can be defeated by new SARS-CoV-2 variants, CCP collected from vaccinated donors after recent breakthrough infections (VaxCCP) evolves with the variants and retains the ability to neutralize them. What makes CCP an even more promising therapy is that there are now many potential donors available in the U.S. who have been vaccinated and had recent breakthrough infections.

...

"An array of data, including randomized controlled trials and careful retrospective studies, show a clear survival benefit when CCP is given to immunocompromised individuals who test positive for SARS-CoV-2. There are also impressive case reports and case series showing that Covid convalescent plasma, especially VaxCCP, is effective in patients with smoldering Covid-19.

...

"the early “major” RCTs that tested the efficacy of CCP on survival in hospitalized patients tested the wrong use case. These studies treated patients who were too sick for too long to benefit from antibody therapy. But the major “negative” trials all showed evidence of effectiveness among people who received CCP earlier, who were not already desperately ill, who were immunocompromised, or who received the most antibodies. Unfortunately, these positive signals, which were consistent with impressive real-world data on Covid-19 and CCP, were buried under the top-line results."

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Earlier posts on convalescent plasma

Sunday, April 25, 2021

The rise and fall of convalescent plasma as a treatment for Covid

 The NY Times follows the story:

The Covid-19 Plasma Boom Is Over. What Did We Learn From It?  The U.S. government invested $800 million in plasma when the country was desperate for Covid-19 treatments. A year later, the program has fizzled.  By Katie Thomas and Noah Weiland

"In those terrifying early months of the pandemic, the idea that antibody-rich plasma could save lives took on a life of its own before there was evidence that it worked. The Trump administration, buoyed by proponents at elite medical institutions, seized on plasma as a good-news story at a time when there weren’t many others. It awarded more than $800 million to entities involved in its collection and administration, and put Dr. Anthony S. Fauci’s face on billboards promoting the treatment.

"A coalition of companies and nonprofit groups, including the Mayo Clinic, Red Cross and Microsoft, mobilized to urge donations from people who had recovered from Covid-19, enlisting celebrities like Samuel L. Jackson and Dwayne Johnson, the actor known as the Rock. Volunteers, some dressed in superhero capes, showed up to blood banks in droves.

...

"But by the end of the year, good evidence for convalescent plasma had not materialized, prompting many prestigious medical centers to quietly abandon it. By February, with cases and hospitalizations dropping, demand dipped below what blood banks had stockpiled.

...

"All told, more than 722,000 units of plasma were distributed to hospitals thanks to the federal program, which ends this month."

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There were also parallel private efforts that mobilized convalescent plasma donation through social media, and via faith based organizations.  I followed some of the science in a series of posts on plasma and plasma donation more generally.  I should note that, although convalescent plasma hasn't emerged as a treatment for Covid-19, it continues to have many very well documented life-saving uses.


Saturday, October 3, 2020

Convalescent plasma continues to be used for treatment of covid-19, but demand is flat

 The WSJ has the story:

Wanted in Covid-19 Fight: ‘Superdonors’ of Convalescent Plasma--Blood banks and researchers are mobilizing to find recovered Covid-19 patients who have high levels of antibodies and are willing to donate regularly   By Amy Dockser Marcus


"Blood banks and researchers are mobilizing to find recovered Covid-19 patients who could be blood plasma “superdonors,” people who have high levels of antibodies against the disease and are willing to donate regularly.

"The hunt has intensified in the past month, after the Food and Drug Administration authorized the use of convalescent plasma, derived from patients who have survived the virus, as a potential therapy for hospitalized patients.

...

"Right now, demand for plasma overall is flat, said Dr. Claudia Cohn, chief medical officer for AABB, a group representing the transfusion medicine and cellular therapy community. She said it could reflect reservations about the strength of existing data, the waning of the pandemic in certain areas of the country, or concerns that the authorization was issued under political pressure from the White House—a suggestion the FDA has pushed back on but that continues to generate debate.

"Doctors said an expected upturn in demand for convalescent plasma didn’t materialize after the authorization, although they are prepared for one should infections surge later this year."

Thursday, May 21, 2020

Blood and plasma: a brief history, from 1628

With all my discussion of convalescent plasma for Covid-19 this week*, here's a historical perspective on the technology and changes in medical practice since the discovery of blood circulation in 1628 that allows blood and plasma to be used in medicine.


A history of blood transfusion: a confluence of science—in peace, in war, and in the laboratory
by Kevin R. Loughlin
Hektoen International, Volume 12, Issue 2 – Spring 2020.

"Since 1628 when William Harvey discovered the circulation of blood, there had been hope that blood transfusion would be possible.
...
"After Harvey’s discovery, transfusion attempts began. In 1665 Richard Lower kept dogs alive by transfusing blood from other dogs.2 In 1667 French physician Jean Denys transfused nine ounces of blood from the carotid artery of a lamb into the vein of a young man. He continued the practice until the third patient so treated, died.3 Denys was sued by the wife of the deceased patient, who presumably died from a hemolytic reaction, but was exonerated. However, the French Parliament, the Royal Society, and the Catholic Church subsequently issued a general prohibition against transfusions.4

"It would not be until 1818 when transfusions were seriously considered again. A British obstetrician, James Blundell, performed a human blood transfusion in the setting of a postpartum hemorrhage.5 However, the debate over transfusions continued over the remainder of the nineteenth century. In 1849 C.H.F. Routh reviewed all the published transfusions to date and remarked in the Medical Times that of the 48 recorded cases, 18 had a fatal outcome and concluded that the mortality rate was unacceptably high.5 The next major advance in transfusion therapy would wait until the turn of the century.

"Karl Landsteiner was an Austrian physician and immunologist. While working at the University of Vienna, he became interested in blood serum work, specifically the factors that led to hemagglutination of red blood cells. This resulted in two landmark publications in 1900 and 1901 that described the evidence of blood groups that he named A, B, and C.6,7 These would later be modified to A, B, and O. Two years later, two of his colleagues, Alfred Von Decastelo and Adriano Sturli, would add a fourth blood type, AB.8,9 Landsteiner would be awarded the Nobel Prize in 1930 for his elucidation of the blood groups.

... in 1912, Doctor Roger Lee demonstrated that O blood could be given to a person of any blood type (universal donor) and that a person with AB blood could receive blood from any blood group (universal recipient).
...
"As blood transfusions became more widespread in medical practice, the concept of establishing blood banks became attractive. In the 1930s Bernard Fantus at Cook County Hospital20 and Carl W. Walter at Peter Bent Brigham Hospital started blood banks. In Boston, Walter’s efforts were viewed with such skepticism and disdain that his facility was relegated to a basement room at Harvard because some trustees thought the storage and use of blood was “immoral and unethical.”21 Fifteen years later he invented the plastic blood bag, which greatly facilitated transfusion therapy.21
...
"In 1940 Edwin Cohn developed ethanol fractionation, the process of breaking down plasma into component products. Albumin, gamma globulin, and fibrinogen were isolated to become available for clinical use.

"In 1944 dried plasma became available for the treatment of combat injuries. Component transfusion therapy became more widely used as the war progressed. The Red Cross concluded its World War II blood program in 1945 after 13 million pints had been collected.11

"In 1961 platelet concentrates became recognized for reducing mortality from hemorrhage in cancer patients. In 1964 plasmapheresis was introduced as a means of collecting plasma for fractionation. In 1971 Hepatitis B surface antigen (HbsAg) testing of donated blood began and in 1992 testing of donor blood for HIV-1 and HIV-2 antibodies commenced.
*************

*here's a recap of my earlier coronavirus posts relating to plasma this week:

Sunday, May 17, 2020


Monday, July 13, 2020

More on plasma, payments, and convalescent plasma

Peter Jaworski gives some more reasons that countries should legalize compensation to plasma donors, rather than buying their plasma products from the U.S.

In Reason:
Americans Get Paid To Donate Plasma. Everyone Else Should Too
Our secret weapon against COVID-19 could be cold, hard cash.  7.2.2020

"American dominance in the plasma market is explained by one simple fact: In America, it is legal and commonplace to pay people to give plasma. Millions of Americans regularly give plasma in exchange for $30 to $50 per donation. The average American donor gives 21.4 times per year, with a per capita collection volume of 113 liters of plasma per 1,000 people. If you add plasma obtained from Germany, Austria, Hungary, and Czechia—the other places where a form of compensation (typically capped at 25 euros, intended only to cover expenses) is offered—paid plasma accounts for a staggering 89 percent of all the plasma used to make plasma therapies for the whole world. Just five countries account for nine-tenths of the world's plasma.
...
"Donor recruitment and retention, staffing, plus marketing costs, combine to make the collection of unpaid plasma two to four times more expensive than just giving money to the donors.
...
"[bans on payment were partly] motivated by the concern that payment attracted people from lower socioeconomic rungs of the economic ladder who are more likely to be carriers of HIV, hepatitis C, and other transfusion-transmissible infections.

"But those concerns no longer apply, partly due to significant improvements in testing technology since the 1970s when the WHO first recommended not paying blood and plasma donors. This improvement in testing happens to form the backbone of arguments among advocates of eliminating restrictions on blood and plasma donation by gay men, which currently require three months of celibacy per the Food and Drug Administration's revised guidance issued this April. But improvements in testing alone are not the reason why plasma for plasma therapies should be considered categorically different from blood and plasma used for transfusions; it is manufacturers' ability to use virus removal and inactivation techniques that marks the stark difference.

"In the 1980s, we discovered that heat treatment was effective against HIV. Much like how washing your hands with soap destroys the coronavirus, use of solvents and detergents are effective against lipid-enveloped viruses, including hepatitis C and HIV. Nanofiltration ensures that only molecules of a certain size—the proteins we want—get through, preventing larger molecules from passing into the plasma pool. Most American paid plasma collection centers are also International Quality Plasma Program (IQPP) certified. This voluntary standard, issued by the Plasma Protein Therapeutics Association, involves additional safety steps including the requirement that any donor's first donation be placed on hold, only to be released with the second donation from the same donor. This holding step gives us an opportunity to test the same plasma twice, avoiding the rare possibility of a virus being within the window period where it cannot be detected. This hold means that if you give plasma once and don't go back, your plasma will be discarded."
**********

With convalescent plasma donation,  the safety check involved in sequestering the first donation until the second one is also tested for infection is not the only set of tests.  For each donation there is also a measurement of how much Covid-19 antibody (IgG) is present, and if it is enough to be therapeutic. So, for example, after each donation I have to wait for those results to find out if I'll be invited to donate again. (So far, at each visit I give a bit over 800ml of plasma, and that donation is divided into four units of 200ml. My understanding is that my units have so far all been administered to hospitalized Covid-19 patients in Fresno and San Jose.)

Monday, May 25, 2020

India NDTV interview on coronavirus, convalescent plasma, etc. (5 minute interview by Dr. Prannoy Roy)

My 5 minutes come at 1:12, but if I've embedded this right the video should begin from there when you start it...

Wednesday, May 27, 2020

Convalescent plasma collection ramps up

Here's a story from the WSJ:
Blood Banks, Pharma Join Microsoft to Sign Up Covid-19 Survivors for Plasma

"A coalition of research institutions, blood banks, drug companies and recovered Covid-19 patients is working to overcome a major challenge in developing new therapies based on survivors’ blood plasma: a shortage of donors.

"With a campaign launched Tuesday called The Fight Is In Us, the group aims to get tens of thousands of people who have recovered from Covid-19 infections to donate plasma using a self-screening tool developed by Microsoft Corp. MSFT -0.17%

"So far nearly 15,000 seriously ill Covid-19 patients have received plasma transfusions in an emergency, expanded-access program authorized by the Food and Drug Administration
...
"The Red Cross has collected plasma from 4,000 recovered Covid-19 donors to date through its website RedCrossBlood.org/plasma4covid, according to a spokeswoman. She said the organization supports the efforts of the coalition but didn’t join it. “At this time, the Red Cross is fortunate to be able to meet the needs of our hospital partners,” she said. “We also have the capacity to ramp up our supply if necessary.”
...
"Despite the unusual efforts to work together, for-profit companies in the coalition also continue to look for donors on their own through digital advertising and other online outreach, according to industry experts.

"Potential donors who go to the thefightisinus.org website start by using a self-screening tool. It asks if they were diagnosed for Covid-19 infection, have been symptom-free for more than 14 days, meet age and weight requirements for blood donation and have ever been diagnosed with HIV, hepatitis C or hepatitis B, which affects eligibility. The potential donors enter a ZIP Code and get a list of nearby donation centers.

"Peter Lee, corporate vice president at Microsoft, which developed the self-screening tool, said donors are currently directed to centers based on location. Coalition members are still discussing ways to determine how donors are allocated.
...
"Some plasma donors might prefer to give to a for-profit plasma company, where they might be reimbursed. Others might choose a local blood bank, where the plasma would be used right away for sick patients in a hospital and reimbursement isn’t offered
...
"In New York and other places affected early in the outbreak, many recovered patients have encountered long wait times to donate"

Thursday, June 18, 2020

Nicola Lacetera, on The Ethics and Economics of Paying Plasma Donors

Nicola Lacetera is among the leaders in studying public views about compensating donors of various sorts. Here he discusses the plasma supply, which is particularly timely given the growing availability of convalescent plasma for Covid-19. (30 minutes)


Monday, May 18, 2020

Plasma and plasma products (such as antibodies) are a big business (and the U.S. dominates the international market)

These days I'm thinking about corona virus covid-19 convalescent blood plasma, which I blogged about yesterday, and about which I hope to say more soon. But that has gotten me to think again about blood plasma generally, which is a source of many therapies, including antibodies, immunoglobulins, that defend against a large variety of diseases.

The U.S. is the Saudi Arabia of blood plasma and plasma products, with both a large domestic commercial market and annual exports valued in the billions of dollars. The reason is largely that it is legal in the U.S. to pay plasma donors, so there's ample supply through a big network of hundreds of  for-profit and nonprofit blood and plasma centers (the nonprofits mostly don't pay donors, I think). In many countries, paying their residents for plasma is repugnant and illegal. Fortunately for their citizens, they mostly don't also suffer from severe shortages of life-saving plasma medicines, because it can be bought from the U.S. (See e.g. my posts on Canada's plasma policies.)

Here are some relevant export figures. They make clear that the U.S. exports billions of dollars of plasma, and tens of billions of dollars of plasma products.




For those who would like to study these data, let me explain where they come from.  (They  include some things that aren't plasma products, and may miss some that are...) It's not so easy to find the U.S exports of exactly blood plasma and plasma products (I needed some help).

In Chapter 30 of the U.S. International Trade Commission (USITC) Harmonized Tariff Schedule (HTS),is the code:
HTS 3002: "Human blood; animal blood prepared for therapeutic, prophylactic or diagnostic uses; antisera, other blood fractions and immunological products, whether or not modified or obtained by means of biotechnological processes; vaccines, toxins, cultures of micro-organisms (excluding yeasts) and similar products:
 Antisera, other blood fractions and immunological products, whether or not modified or obtained by means of biotechnological processes"

That sounds good, but it includes (aside from plasma products) things that I don't want to include e.g. Malaria diagnostic test kits, and Fetal Bovine Serum.

On the other hand the subcategory 3002.12.00  is for "Antisera and other blood fractions" which includes sub-subcategories for things I do want to include:
3002.12.10 Human blood plasma.
3002.12.20 Normal human blood sera, whether or not freeze-dried
3002.12.30 Human immune blood sera

And then there are are codes 3002.13.00, 14.00, and 15.00 which cover the promising (very similar) categories in which most of the immunoglobulins are probably found, but maybe some other things too:

Immunological products, unmixed, not put up in measured doses or in forms or packings for retail sale
Immunological products, mixed, not put up in measured doses or in forms or packings for retail sale
and
 Immunological products, put up in measured doses or in forms or packings for retail sale.

The place to go to turn these numbers into export figures is dataweb.usitc.gov  (But getting data there isn't completely straightforward, and I got help from Julia Fabens.)  The table above shows that whole plasma itself has over $2 billion of annual exports from the U.S., and together with plasma products, including those involving antibodies (immunological products) there are almost $20 billion of exports from the U.S.

So, I'm guessing that soon, if clinical trials show that antibodies against covid-19, are useful, they will become readily available, commercially, in plasma and in pharmaceuticals.  A year ago, those human antibodies didn't exist, and so there was no way to use it to help patient zero or the next many thousands.  But now there's a lot of it, more each day, in the blood of recovered patients.  And there's a whole industry devoted to collecting it and purifying the antibodies into "immunological products." 

I hope human antibodies against covid-19 are clinically useful, to help mitigate and cure the disease if not to prevent it, because my sense is that a vaccine is (at least) many months away.
102,597,746 2,627,504 1,586,634
102,597,746 2,627,504 1,586,634

Friday, July 17, 2026

Is Healthcare a Moral Marketplace?

I was delighted to be invited to discuss healthcare with Drs Wendy Dean and Matt Ramsey.  We had a discussion ranging from the health care markets described in Moral Economics, to the experiments on trust in medicine conducted by my colleague Marcella Alsan And there's a transcript for those who prefer to read than to listen.

 

53 min 35 sec

Episode Description
What does a morally defensible, healthy, legal, commercial marketplace look like, and how can we design one for healthcare? Nobel laureate Alvin Roth, Professor of Economics at Stanford University and the George Gund Professor of Economics and Business Administration Emeritus at Harvard University, joins us to about his new book, Moral Economics:  From Prostitution to Organ Sales, What Controversial Transactions Reveal About How Markets Work.

 

And here's a largely A.I. generated transcript (which I've edited very lightly and reproduce here with permission): 

Ep. 079 Alvin Roth FINAL June 29 2026.mp3

Wendy Dean, MD: [00:00:00] This is a moral matters podcast. Good human healing. Well, I was a science kid in college, but I do remember taking econ 101, and I loved it because it made so much sense. But I was also really stubborn and I was not going into the family. Well, shall we say the business of business, so to speak. What about you, Matt?

Matt Ramsey, MD: [00:00:32] Well, I loved economics 101. Economics 201 was my downfall. Uh, I got in way over my head in economics way too early. And that was the end of that. So beyond supply and demand, beyond macroeconomics, that was the end for me. And I too was a science kid. And, you know, economics is somewhat science based and can make sense mathematically, but there was a lot of soft, gushy stuff in economics that I couldn't really get my arms around. So it was like, I'm out. Let's get me back to the chemistry lab, please.

Wendy Dean, MD: [00:01:19] Yeah. Well, I mean, today we're getting a master class in market design from a Nobel Prize winner.

Matt Ramsey, MD: [00:01:25] So yeah. So buckle up. Um, this is a rare privilege. Um, you know, it's I don't know that I've talked to many Nobel Prize winners in my life, and I probably would be safe to say probably it's a one and done for me. So I'm going to really relish, uh, this conversation we have tonight.

Wendy Dean, MD: [00:01:47] Yeah. Well, our guest today is Alvin Roth. He's the Craig and Susan McCaw professor of economics at Stanford University and the George Gund Professor of Economics and Business Administration emeritus at Harvard University, a pioneering expert in the field of market design. He was awarded the Nobel Prize in Economics in 2012. His latest book is Moral Economics, and in it he asks what a morally defensible, healthy, legal commercial marketplace might look like in controversial markets such as organ sales or prostitution. But we'd like to ask, what does a morally defensible, healthy, legal commercial marketplace look like in health care? And how can we design it?

Matt Ramsey, MD: [00:02:27] That is a great question. I'm Matt Ramsey.

Wendy Dean, MD: [00:02:32] And I'm Wendy Dean, and this is the 43 CC podcast. Welcome to the show.

Alvin Roth, PhD: [00:02:41] Thank you. Happy to be here.

Wendy Dean, MD: [00:02:45] All right. Can we just start with the very basics. What does moral economics mean.

Alvin Roth, PhD: [00:02:52] So moral economics is,  I guess, an economics that tries to understand where moral questions are important and critical and unavoidable, and where what sometimes appear to be moral questions are really just questions about what trade offs we can and must make and how we should make them.

Matt Ramsey, MD: [00:03:11] So how does the average Joe know when they encounter a morally healthy market? Or in a broader sense, I guess, a morally healthy economy?

Alvin Roth, PhD: [00:03:23] Well, I think our intuitions about moral decisions of all sorts come to us fairly quickly. I think it's now a commonplace observation that we quickly decide what we think is right and wrong, and then we look for reasons to explain why we feel that way. So I think that's as true in  economic environments as it is in other environments.

Matt Ramsey, MD: [00:03:46] So you write that stories about market design often begin with failure. Failure to provide what you describe as thickness, which I love that term, by the way, to ease congestion or to make participation safe and simple.  that sounds very much like health care today.  can you talk to us a little bit about what a failing or unraveling market, as you describe it looks like, and what happens when those on the receiving end, specifically patients are unable to exercise their control in that market?

Alvin Roth, PhD: [00:04:25] Okay. So that's a good question. Unraveling and control.  let me spend a moment talking about how those play out in non-health care markets.  when I speak about unraveling, I'm often talking about decisions unraveling in time, becoming earlier and earlier  than would be a really timely time to make the decisions. Because decisions take time or because some decisions have to be planned in advance. And, and therefore, people can't wait to take care of all the decisions that they have to, which will be time consuming at a time when they would like to. So just incidentally, American doctors get their first jobs through a centralized clearinghouse that I've had a hand in helping design. And that's because before there was such a clearinghouse, doctors often were  asked to say yes or no to job offers years before they graduated from medical school, before they could properly plan. And this was a burden also on the employers. They had to hire doctors before they knew what kind of doctors they would become. That's called unraveling in time.It’s one of the places where you see worries about the timeliness of decision.

Alvin Roth, PhD: [00:05:36] One controversial medical market right now is the controversy over medical aid in dying.  So there are now a dozen jurisdictions in the United States, and there'll be a few more  come  the fall that have legal medical aid in dying. And there are a number of countries that allow medical aid in dying, Canada being one of them. And the Canadian Supreme Court had a very interesting decision, explanation of its decision to legalize medical aid in dying in Canada. What they said is  Canadians are entitled to security in their lives, and if there's no medical aid in dying, then there may be people with terrible diseases who feel compelled to take their own life while they still can, because they won't be able to get aid if  their illness becomes unbearable. And so to prevent that, to prevent that unraveling in time, that might force people to take their own life, the Canadian Supreme Court said, we're going to authorize Canadian doctors, under some circumstances, to give aid to people who are dying so that they don't have long, lingering, painful deaths.

Wendy Dean, MD: [00:06:44] That is such a fascinating topic. Medical assistance in dying is such a timely topic right now.

Alvin Roth, PhD: [00:06:54] Where are you located?

Wendy Dean, MD: [00:06:55] I'm in Pennsylvania. Well, we're both in Pennsylvania. Jill is in Boston.

Alvin Roth, PhD: [00:07:00] Okay. Well, so I'm not sure what the Pennsylvania story is, but New York will have medical aid in dying  in the fall. And I think so will Illinois. They're the latest two states. And there are some states that don't have residency requirements. And of course, there are countries that you can go to, to, to access medical aid in dying. So one of the things about bans, of course, is they they put up barriers, but they don't necessarily stop people from accessing things that they want to access.

Matt Ramsey, MD: [00:07:32] Yeah, exactly.

Wendy Dean, MD: [00:07:33] So true. And, you know, just this is just a question that I'm going to throw out there. But, um, on the back end of it, we're offering medical assistance in dying while people are still struggling to get access to the full range of health care.

Alvin Roth, PhD: [00:07:50] Yes. And of course, one of the controversies about medical aid in dying is, people who are opposed to medical aid in dying laws say, some people just want to access medical aid in dying because they don't have access to medicine, to medical care. And we'd be better off working as hard as we can to give everyone good access so that they don't think of medical aid in dying as an attractive alternative. And of course, there's an association of palliative care doctors in the United States who deal with hospices, and their position is interesting. They have a policy statement that says they are studiously neutral on the question of whether medical aid in dying should be legal, but they worry about the slippery slope that might come with legal medical aid in dying. But they also acknowledge that there's covert medical aid in dying. That is, even in places where it's not legal, there is medical aid in dying because the same  pharmaceuticals, the same drugs that can ease pain can shorten life. And so they know, and the doctors I talked to know of cases where someone in great pain is given enough morphine so that they won't wake up in the morning.

Wendy Dean, MD: [00:09:03] Yeah. Yeah. There's no easy answer there, which is probably why you're studying it.

Alvin Roth, PhD: [00:09:12] Oh, yeah.  I don't propose answers. I mean, the answers to many of these questions are above my pay grade.

Wendy Dean, MD: [00:09:19] You know.

Alvin Roth, PhD: [00:09:20] I know you've looked at my earlier book called Who Gets What and Why, and that was sort of an optimistic book about market design. It was a book that says sometimes markets are broken and we can fix them. It was a good feeling book for an economist. And this is a less optimistic book, Moral Economics. This says there are markets that aren't working very well at all. They're broken, but it's going to be hard to fix them because we don't necessarily agree on what we want them to do. And that coming to agreement is going to be an important part of, of trying to improve the function of these markets. And it may not be easy to do.

Wendy Dean, MD: [00:09:53] Yeah. Well, one of the things that you write about is that the importance of reputation and trustworthiness in health, health care markets, like in healthy markets as a whole. What happens when those elements aren't viewed as priorities, when trustworthiness and reputation take a back seat to something else?

Alvin Roth, PhD: [00:10:13] Well, so one of the big points in my book that I look at in a lot of controversial markets is that markets need social support to work well, and so do bans on markets. But medical care sometimes suffers from lack of social support that it needs to work well. I have a colleague here at Stanford named Marcella Alsan, who studied the perception of American medical care among black Americans. And one of the things she finds is that everyone she talks to, whether or not they're highly educated, know about the Tuskegee experiments. They know that there were unethical experiments in which black men were left untreated for syphilis, and that that gives them some distrust of the American medical system. And she ran an experiment in a black barbershop in Oakland. Apparently, hypertension, high blood pressure is quite common among black men. And so she had an experiment in which she  came armed with a leaflet that said, if you want, I can put you in an Uber right now and take you to a nearby clinic. Where this doctor (and there would be a picture of the doctor on the leaflet) will take your blood pressure and talk to you about it and what you might do about it. And the experimental control was either the leaflet had a white doctor or a black doctor, and she followed not just how many people went to see the doctor, but often they had high blood pressure and the doctor would recommend that they do something about it. She  tracked how often they took the advice of the doctor, and it turned out that black doctors were more effective at getting young black men who had apparently very high blood pressure to do something about it.  So this question of trust doesn't isn't just a hypothetical question. It's a question of compliance. You know, someone who's giving you advice and is it advice that's good for you or good for them? And believing that it's advice that's good for you makes it more likely that that you'll follow it.

Wendy Dean, MD: [00:12:16] Yeah.

Matt Ramsey, MD: [00:12:18] So I'm, I'm fascinated. I'm fascinated in both of your books, but about the whole concept of market design, you know, that, you know, my economics 101 in college, where it was a supply and demand was. So, you know, that was so kind of superficial. And the fact that you can actually design markets. Um, and have them work effectively is fascinating to me. Um, you know, one, one concern that you talk about in market design is objectification, you know, the fear that the act of putting a price on certain things and then buying or selling them might move them into a class of impersonal object to which they should not belong. That is, they risk losing their moral value. Uh, I guess a question very specific to health care is how can we maintain a moral value in health care in, in a, in a market that demonstrates some elements of objectification?

Alvin Roth, PhD: [00:13:21] Okay, that's a complicated question, for which I bet we'd have different discussions on different parts of health care. But one place it's come up a lot for me is in organ transplantation and donation. And so,  in particular, I've been involved with kidney transplantation and how it's organized, and it's against the law almost everywhere in the world to pay a kidney donor, a living kidney donor, or the family of a deceased donor for their donation. So,  kidneys are a little special when it comes to organs because healthy people have two and can remain healthy with one. And so healthy people can donate a kidney to someone who's dying of kidney failure.  but we have 130 000 new cases of kidney failure in the United States each year. And we do fewer than 30,000 transplants each year. So most people who might be able to profit from a transplant will die without receiving one, because there's a big shortage of kidneys, we get about 27,000. About 22,000 deceased donor kidney transplants a year in the United States, and not quite 7000 living donor transplants. So a lot of the work I've been involved with has involved kidney exchange, ways to increase the chance that someone can get a compatible kidney from a living donor without involving any payment to the donor, so that just circumvents that problem.  and we've made a lot of success:  on a different kind of podcast, I could tell you about victory after victory and how we've increased the number of transplants, but it's in a war that we're losing. The incidence of kidney failure has risen faster than the number of kidney transplants.

Alvin Roth, PhD: [00:15:05] But so, so one thing that comes up when economists see there are not quite 100,000 people waiting for a deceased donor kidney in the United States now, and they would be more on that waiting list if, if it were more possible to, to survive the waiting list and get a kidney.  when economists see a long line of people waiting for a scarce resource, we know that prices aren't being allowed to increase the supply of the scarce resource. And indeed, That's true around the world. It's  against the law to pay a donor for a kidney. Everywhere in the world for  it's against the law to pay a living donor for a kidney. Everywhere in the world except in the Islamic Republic of Iran. And I've read some of the Shia fatwas on that. And they're interesting to read. But the concern that you raised that  by allowing people to be paid for kidneys, we might be treating people more as means than as ends, we might be commodifying them, treating them as a carrier of a kidney rather than as a person, that plays a significant role in the distaste, the repugnance of, not allowing kidney sales. Now, it's not just kidneys that  people feel that way and legislators have legislated that way. There are other substances of human origin that play important roles in medicine, and one of them is blood and blood plasma.  So ever since World War One, when  we started to have blood banks and blood transfusions, blood has played an important role in medicine.

Alvin Roth, PhD: [00:16:43] And increasingly now, plasma  plays a very important role. The World Health Organization  has a list of essential medicines. If you want to start a hospital anywhere in the world,  they have a list of things that you have to have in your pharmacy. And on that list are many plasma pharmaceuticals, pharmaceuticals made from human plasma, which so far still has to be donated by a person, by a living, healthy person. But many countries in the world, including  a lot of the countries in Western Europe, not all of them, have laws against paying plasma donors. And so they would have great shortages of plasma. None of the countries that that have laws against paying plasma donors are able to collect as much plasma as they need from unpaid domestic donors. But it turns out there isn't this great shortage of plasma in Europe,  Because you can buy the plasma you need from the United States. In the United States, we allow plasma donors to be paid, and we export tens of billions of dollars a year of plasma pharmaceuticals to save lives around the world. And indeed, many of the biopharma companies that collect plasma from paid donors in the United States are subsidiaries of biopharma companies in countries like Spain, where it's illegal to pay plasma donors. But I guess their feeling is it's immoral to pay for plasma. It commodifies the donor. And besides, you can buy all you need from the United States. So.

Matt Ramsey, MD: [00:18:12] Exactly.

Alvin Roth, PhD: [00:18:13] So, you know, so out of sight, out of mind is one of the ways of dealing with  moral complexities.

Wendy Dean, MD: [00:18:21] I could have had 1 or 2 fellow medical students who were supplementing their income in medical school with plasma donation.

Matt Ramsey, MD: [00:18:29] Count a third.

Alvin Roth, PhD: [00:18:33] There's a recent paper by two economists about  another controversial market I talk about. They're not all medical markets. Another controversial market I talk about is payday loans. People who live paycheck to paycheck have more trouble getting loans than you and I do. And they pay higher interest rates. But  if they have regular paychecks, they can get a loan secured by their next paycheck at high interest rates. It's not a great part of the financial system at all. But someone did a study, two economists did a study that looks at the opening of plasma donation facilities, where plasma donors are paid. And they find that in regions where plasma donation becomes available, payday lending goes down.  In other words the same urge, the same need that says, you know, I, I need my car to get to work and it's just broke down and it's going to cost something to fix it. That same need could cause you to go to a payday lender and have a loan at a higher annual interest rate than your credit cards have, because these guys don't have credit cards. Instead, you could donate plasma  and save lives. So, so you know, there's something. The world is a complicated place. We might want to live in a world where no one felt a need to donate plasma for money. But, uh, just passing a law against it doesn't make the need go away. And it's, it's a pretty good thing to do. I sort of hope that people who sell their plasma are proud of it. I was a very early adopter of Covid, and when I started to get well, the local Stanford blood bank, which doesn't pay for plasma, wanted my plasma as convalescent plasma. And so I donated plasma after I recovered for a couple of months, unpaid, until they fired me when my antibody titer got too low.

Matt Ramsey, MD: [00:20:27] You're of no use to us anymore.

Alvin Roth, PhD: [00:20:29] Yeah, exactly. But I no longer donate plasma, although I still donate whole blood because in the United States we get our whole blood from unpaid donors. And so it's a good thing to do, but I don't feel any urge to donate plasma. There's plenty of plasma. I don't want to take jobs away from people.

Matt Ramsey, MD: [00:20:46] Who need it.

Alvin Roth, PhD: [00:20:47] Right. So a lot of the argument about not paying for substances of human origin, I think, is, is based on bad economics. It's that people won't want to do it anymore if, if other people are paid for it. And there's some truth in that: I don't want to donate plasma anymore, but there's no shortage of plasma because people are paid for doing it. So, I think that carefully regulated markets in which people can be paid for plasma are a good thing, because plasma saves millions of lives every year around the world.

Wendy Dean, MD: [00:21:18] Yeah. So you've mentioned the term the phrase repugnant transaction a couple of times. Could you just define it for the listeners?

Alvin Roth, PhD: [00:21:28] Okay, so I use that as a technical term. Repugnance, of course, is a word that has existed in English for a long time. And I started using it when I was writing about the repugnance of paying donors for kidneys, but in general, and I've now started to see it all over. There are many causes of controversy, moral controversy, moral contests that I talk about in my book, but one kind that's really interesting to me involves what I call repugnant transactions, which are transactions that some people want to engage in and other people think shouldn't be allowed, and particularly the other people who think it shouldn't be allowed feel that way because of moral or religious arguments, not because they're personally harmed by the transaction. And indeed to make it clear, I say it might even be that they can't even tell if the transaction has happened unless someone tells them. By this definition, same sex marriage is a repugnant transaction. And when I say that, I don't mean that I disapprove of it or that you should, but that some people want to marry each other and other people don't think they should be allowed. And you can't tell whether someone is married unless they tell you which they might do by wearing a wedding ring.  So it's not because of the direct personal harm the people who object to same sex marriage suffer when someone gets married.  but of course it was a giant political issue for the first part of this century.

Alvin Roth, PhD: [00:22:54] It became legal in the United States and maybe anywhere for the first time,  in 2004 in Massachusetts from a court decision. And it became legal in every state in the United States in 2015 with a Supreme Court decision about equal protection under the law. but it was a tough fight for, for a long time. You know, the idea of same sex marriage had  been around for decades before without making any progress. And of course, there are other controversies, many, many controversial markets in the United States get adjudicated by the Supreme Court, and some of them are medical in nature, like abortion. And so what we've seen recently is those can go both ways.  Roe v Wade had established a personal right to abortion under some circumstances for Americans that stood for 50 years. And then the Dobbs decision sent it back to the States. And in his concurring opinion to the Dobbs decision overturning Roe v Wade, Justice Thomas had said that there were other judicial decisions that he thinks are mistakes that we should reconsider, including banning. There were laws that banned selling contraceptives, for instance.  and of course, similar to the abortion laws, we've now had controversies about, uh, aid in, in reproduction, like in vitro fertilization. So there are a number of medically adjacent markets that, that are contested in this way.

Wendy Dean, MD: [00:24:36] Yeah. Well, I'm, I'm going to ask you to, to come up, you know, to 50, zero zero zero feet and think about health care as a whole. Um, so for decades, healthcare has been treated like almost any other market yet it is a little bit different in some ways. It is. And I think there are some people who would argue that it is repugnant. It has repugnancy at its core, meaning that we're profiting in some places from other people's misfortune. Right. So how do we square health care decisions driven by money rather than morals? Especially when the AMA code of ethics says the practice of medicine is fundamentally a moral activity And so we're asking clinicians to behave in ways that will benefit the system, but might work against the clinicians oaths, for example. So the administrators want them to act in one way. They don't want to act in that other way. The patients don't know the difference. Maybe who's being who's being asked to work in what way would you define that as a repugnant system? And if so, how do we mitigate it?

Alvin Roth, PhD: [00:25:52] Okay. So when you talk about medicine as a whole, you're talking about lots of different kinds of transactions. And as a market designer, I find myself forced to get down in the weeds and deal with details. So, so I can tell you a little bit about, you know, artificial reproductive technologies. I can tell you a little bit about abortion. I can tell you a little bit about transplantation. When you say health care as a whole,  I get a little nervous because  that's a big bundle of things. But let me start by saying that I don't think  there's much traction in the idea that medicine as a whole might be repugnant because doctors profit from people's illness any more than farmers profit from people's hunger or  roofers profit from people's desire not to be rained on. Uh, on the contrary, I think of all those people as, as helping people meet their needs, right? Doctors help you when you're not feeling well, or maybe they ideally, maybe they help you to avoid not feeling well by, by practicing preventive medicine. You know, farmers grow food, so we're not hungry. And so we don't have to grow our own food. We can be doctors. I mean, there was a lot less, uh, medical care provided for people before the invention of agriculture. Uh, so filling needs is not a wrong thing, and filling needs as a way to earn your living is often the way we fill our most basic needs. Because if you couldn't make a living as a farmer, there'd be a lot fewer farmers. If you couldn't make your living as a doctor, there'd be a lot fewer doctors.  If people who wanted to do health care, if physicians had to make their living some other way, they'd be a lot less experienced in health care.

Alvin Roth, PhD: [00:27:40] They'd spend their days, you know, doing, doing lawn care or whatever we made doctors do instead of being paid for health care. And they'd have a lot less experience doing knee surgeries or, diagnosing unusual illnesses. So. So I'm very glad that my medical care is provided by professionals who can devote themselves full time to medical care and who can, you know, get educated in medicine. That being said, you know, we're a rich country that doesn't have universal health insurance. So there's lots of things to worry about. And market designers worry about these things. There'd be a lot less repugnance in the world, There'd be a lot less moral contest about markets if there wasn't so much income inequality and wealth inequality. If we were all roughly as rich as each other, then  the differences in what we consumed would be just a matter of taste as opposed to what we could afford. So that's a giant problem, not just of medicine, but of global economics, right?  we're doing better and better at providing resources and making resources less scarce. And a sign of that is people are living longer than they used to and living longer, healthier lives. That's a good sign of human progress over the last 200 years and over the last hundred years, too. So some of that is medicine, some of that is public health. Some of that is good nutrition. I mean, a lot of things go into helping people live longer, healthier lives. But medicine is a significant part of it. So. So I don't think you have to feel bad about being a physician.

Wendy Dean, MD: [00:29:19] Uh, yeah. Um, so I spent an awful lot of time when I was reading your two books, thinking about just that, just that question of would this, would this largely not be an issue if there were more income equality? And it was so I'm so grateful to hear you say that.

Matt Ramsey, MD: [00:29:40] So, um, in, in, uh, the book Moral Economics, you write about how we should think about building societies that support human welfare, balancing the rights of people to pursue their individual and mutual goals with the need to protect society's most vulnerable members from harms that may arise from markets, including black markets growing without boundaries. So let's talk a little bit about boundaries. Um, you know, what does the point of no return look like in a poorly regulated market. And you know, how soon do new markets need regulation? And who is it? You know, you've just said that regulation can occur on multiple levels from multiple entities. Like who? Who is it who decides when and how regulation happens?

Alvin Roth, PhD: [00:30:34] Okay, so let's talk about the American experience with alcohol.

Matt Ramsey, MD: [00:30:39] Okay. So let's.

Alvin Roth, PhD: [00:30:42] Yeah, we can meet and have a drink later. But in the 1920s through the early 30s, we passed a constitutional amendment that made it illegal to produce or sell most alcoholic beverages, didn't make it illegal to drink them, but it made it illegal to to produce or sell them. Nevertheless, the consumption of alcohol didn't drop to nothing. On the contrary, it stayed pretty much as it had at pre-prohibition levels after an initial dip, and it gave rise to serious organised crime. People who competed for market share with machine guns. The Saint Valentine's Day massacre is a famous example. Al Capone's gang was the victim of that, incidentally, not the perpetrator, But he was a famous alcohol prohibition era gangster. Um, so in the early 1930s, we amended the Constitution again to repeal the amendment that banned the production and sale of alcohol. And so today we have legal regulated markets for alcohol. And they're regulated in lots of ways. Not every restaurant gets a liquor license. Uh, children can't buy alcohol. People under 21, not just children can't buy alcohol legally. Uh, there are different state rules in different places. I lived in a county in Illinois when I lived in Farmer City, Illinois, where, alcohol wasn't sold on Sundays, for instance.  so there are regulations. The problems of alcohol have not gone away with the legalization of alcohol.

Alvin Roth, PhD: [00:32:23] There's still alcoholism and there's drunk driving. There are organizations like Alcoholics Anonymous that  help people try to deal with alcohol addiction. So the problems of alcohol didn't go away, but the gangsters did. You can't buy moonshine whiskey from gangsters anymore. On the contrary, you buy it from fancy  Scottish, producers who age their whiskey in American oak.  And, you know, it's a sign of great prosperity to to be a judge of fine whisky. Uh, so, but the problems of alcohol didn't go away. But we're trying to manage them and we've been trying to manage them now for decades, and we like that better than we like the Wild West criminal market for alcohol. Now, that's the kind of market we have for opioids these days, right? There's great violence associated with the supply of, of heroin, for instance, heroin, fentanyl, I mean, all sorts of things. Fentanyl is funny, of course, because it's a prescription drug as well. I've had fentanyl, I've had too many surgeries and I've had fentanyl in many of them. Uh, you know, it comes and goes quickly. It's a good hospital kind of pharmaceutical, but it can also be mixed with heroin and, and cause people to have to be uncertain about what doses they're taking.

Alvin Roth, PhD: [00:33:50]  so getting your opioids from criminals on the street is much more dangerous than getting them from pharmacists, who would be responsible for what you're getting. So I think we're at a point where we have to rethink the market for heroin. and again, it's because not just that markets need social support, but bans on markets need social support. So one of the things I talk about in the in the moral economics book is why is it so easy to buy drugs but so hard to hire a hitman? you know, we have very little commercial murder in the United States. It doesn't even make it into the national crime statistics. And part of the reason is, if I suggested to you that I was looking for a hitman, you'd be surprised and horrified. And later you might decide to call the police. You know, if I pressed you to tell me where I could find a hitman in  Pennsylvania, and the police, when you call them, they would be interested. They would say, you know, when he comes to Philadelphia, tell them to go to this bar and bring $5,000 in 20s and ask for for Sam and Sam will take care of him. And indeed, the way we catch most of the people who try to hire hitmen as they end up trying to hire a policeman.

Alvin Roth, PhD: [00:35:06] Undercover policeman. But if I said to you, I'm coming to Pennsylvania, and I wondered if you would know where I could buy some heroin in Pennsylvania, you'd also be very surprised. But you wouldn't call the police. And you may even know where heroin is sold in Pennsylvania. Um, so we just react, you know, the ban on hitmen has much more social support from from you, from the police, from, everyone than the ban on heroin, because there are people who live in neighborhoods where heroin is sold and, and, you know, you can learn to live with it. So, coming back to heroin and to other kinds of drugs, we can't even in the US, we can't even keep drugs out of our prisons. And prisons are the places where there's the most possibility of using police and armed methods for keeping control. So the chance that we can use police and military methods to keep drugs off the street, we've pretty much convinced ourselves we can't do that. And so it might be time to start thinking, as we did at the end of prohibition, of how are we going to reduce the harm that this criminal market. We so much don't like heroin.

Alvin Roth, PhD: [00:36:16] We made drugs of that sort illegal to sell. And as a result, we have a market for just those drugs run by criminals. And are we happy with that? Maybe we should think about legalizing and then regulating. You know, I say in the book that having a legal market for heroin doesn't mean there'd be vending machines in elementary schools for heroin. You know, it would presumably be something more like the prescription drug market. And it might come together with diagnoses that in order to be prescribed heroin also required other kinds of treatment for your disease of addiction to heroin. And maybe we could do a better job because the violence we saw of prohibition era gangs In the 1920s, and 30s is not on a bigger scale than the violence we're seeing around the world associated with drug cartels today. So so we have a lot of trouble in the United States as a consumer of heroin and other kinds of drugs. But there's countries where drugs are produced, where the drug cartels are alternate governments. I mean, they're in military conflict with the authorities. So so there's lots of harm coming. It might be time to think about harm reduction and and at least in some dimensions, treating opioid addiction more like a medical problem than a crime.

Matt Ramsey, MD: [00:37:40] That drives us right back to the repugnancy discussion, though. So it's not often that we get to speak with the architects of health care's infrastructure. So as a person who directed the redesign of the national Resident Matching program's matchmaking algorithm, we have to ask you about the match program. As a practicing physician, one of the most memorable days in my life was the day I matched in orthopedics. And it is a very.

Speaker 4: [00:38:10] What year was that?

Matt Ramsey, MD: [00:38:11] Oh, that was 1990. 1990. Okay.

Alvin Roth, PhD: [00:38:16] And you're talking about your residency or did you do a specialty?

Matt Ramsey, MD: [00:38:19] I did both actually. And I, I can tell you the story about markets unraveling because we didn't have a match for fellowships for many years. And it was a complete circus.

Alvin Roth, PhD: [00:38:32] I remember I actually helped  that organization to get some fellowship matches.

Matt Ramsey, MD: [00:38:37] Yeah. So, so. You know, one of the, when we talk to folks about the residency match, we have, I mean, one, one of the things that the residency residency match has is an antitrust exemption. Um, and Until recently it's been unchallenged. And I guess a question, and because I have some very strong thoughts about this, can can something like a residency match exist without the exemption or regulation?

Alvin Roth, PhD: [00:39:14] So, so I remember the circumstances in which that exemption came. It came in reconciliation, in a pension bill.

Matt Ramsey, MD: [00:39:26] Of course, buried deep in some other legislation.

Alvin Roth, PhD: [00:39:30] Yeah, exactly. Exactly. Uh, and before that, the match had operated for many years without an antitrust exemption. What now? Now, I've talked to lawyers about this, and they say it's a real antitrust exemption, but it does have an exception. What it says, well, this is not the legal reading,it  says running a match is not itself a violation of the Sherman Antitrust Act. Well, maybe maybe the Clayton Antitrust Act, I forget. But but if you can show harm to to doctors or to residents or to hospitals, you can still sue under the antitrust laws. But you have to show harm. You can't just say that it's a per se violation. Now, that's not the plain language of the of the legislation. It's my interpretation. but the reason it came about was there had been a class action, a double class action lawsuit against the match and all the medical associations, associated with it and all the hospitals that involved themselves in resident training. And when I say double class action, a class action lawsuit has a class of, of plaintiffs. And this was a class action lawsuit on behalf of all doctors who had had residencies, which is to say all doctors, but it was suing the class of all hospitals that employed residents And what that meant was  the legal defense bills for the hospitals. Every hospital had to have its own law firm. And I would meet with some of these guys in those days. And their tickers were running.  I was at Harvard and I didn't like to travel for this. So they would come to me and they would be these big groups of, of, of lawyers with their, with their meters ticking.

Alvin Roth, PhD: [00:41:17] So there was a lot of pressure to try to settle. And the, the class action lawsuit, which was brought by 16 law firms on behalf of, I think half a dozen named residents, they appeared to be interested in a settlement. That was what they were shooting for.  And the reason they were suing a whole class of hospitals was to make it easier to to get a settlement, to extract a settlement because the the defense costs were so high. But at the same time, that was sort of a strategic error because every senator has hospitals. So  the AMA and some of the related organizations,  were able to get legislative relief that said, you'd have to prove harm. You can't just say what the antitrust laws do, among other things, is they forbid conspiracies in restraint of trade. And the main  object of the suit was that the match itself was a conspiracy. They say, what could be more conspiratorial than than a centralized clearinghouse that, uh, you know, that tells every doctor where to go. And one of the arguments against that was what could be more conspiratorial than the New York Stock Exchange, which at every moment in the day determines the prices of all the commodities, all the all the securities that are being sold on the stock exchange. So the argument in defense was, this is a marketplace. That doesn't mean that it violates the antitrust law. But the exemption cut off this source of contention through class action lawsuits. So it's true that that one of the House committees is now thinking that that they should repeal that exemption, and maybe they will. I don't think that will necessarily interfere with the match if it doesn't lead to more extensive litigation.

Matt Ramsey, MD: [00:43:07] Well, I can just tell you personally, unraveling of that market will be a wild experience because I've lived through an unmatched fellowship kind of, and it was no fun. I mean, I can tell you that once the match happened, it was a big sigh of relief that we could.

Alvin Roth, PhD: [00:43:26] Well, so let me tell you a story about the organization of the fellowship Orthopedic surgery matches of which there are many, because orthopedic surgeons divide up the parts of the body. You know, there's hand and wrist and shoulder and elbow. And, you know, it's sort of like going into an old timey butcher and seeing the cow.

Matt Ramsey, MD: [00:43:48] Give me some shoulder.

Wendy Dean, MD: [00:43:49] With better tools, though.

Speaker 4: [00:43:50] Yeah, yeah, yeah.

Alvin Roth, PhD: [00:43:52]  so that was a market that had unraveled and people were getting exploding offers as early as the second year of their five year general surgery residency. So I started to talk to orthopedic surgeons when I heard about these problems. And I would say to them, gee, can you really tell who's going to be an orthopedic surgeon at the second year of their general surgery residency? And the first reactions I got said, well, you know, that's not a problem. I mean, we can tell who's going to be a good surgeon. And then sometime later, they came back to me and they said, you know, actually there is a problem. The problem is not who's going to be a good surgeon. It's that sometimes we've hired people who, when they arrive three years later to be orthopedic surgery fellows, turn out to be assholes.

Alvin Roth, PhD: [00:44:43] And what they meant By that is they're disruptive in the O.R.. They're not nice to the nurses, things like that. And you couldn't detect that when they were second year surgical residents because as second year surgical residents, they were still polite to everyone, but that if you could have delayed hiring them until they had time to blossom, then you could have avoided some problems.

Speaker 4: [00:45:01] In the Or.

Matt Ramsey, MD: [00:45:02] Oh, the stereotype of orthopedic surgeons, my lord.

Speaker 4: [00:45:08] These were.

Alvin Roth, PhD: [00:45:08] Orthopedic surgeons telling.

Speaker 4: [00:45:09] Me this. Yeah, of.

Matt Ramsey, MD: [00:45:10] Course, of course.

Wendy Dean, MD: [00:45:13] Yeah.

Alvin Roth, PhD: [00:45:14] So there's a problem on both sides of hiring people well before you have enough information. And that's of course each year there are more fellowship matches as,  subspecialties  that don't have matches run into the same problems  that the market ran into in the 1950s and the 1980s and the 1990s.

Matt Ramsey, MD: [00:45:39] Yeah. For sure. Well, al, thanks so much for being here. This was a wonderful conversation. Um, you know, obviously we're talking big issues and, um, you've solved a lot of issues in health care with.

Alvin Roth, PhD: [00:46:03] Very good. Well, I had a lot of fun writing the book. I learned a lot, and I'm glad to have had the opportunity to talk to you about it.

Wendy Dean, MD: [00:46:09] Yeah. Thank you so much. I really loved reading both of the books. Not not just not just the optimistic one, but moral economics was great too.

Speaker 4: [00:46:17] Well, I'm.

Alvin Roth, PhD: [00:46:17] Still optimistic about market design.

Alvin Roth, PhD: [00:46:20] But, you know, nobody said it was going to be easy.

Speaker 4: [00:46:23] Right.

Wendy Dean, MD: [00:46:25] Right. Well thank you.

Alvin Roth, PhD: [00:46:26] Thank you.