The Economist on blood plasma

The Economist comments on Canada's repugnance towards paying Canadians to donate blood plasma (when you can buy as much as you need from U.S. donors..see previous posts.)

Vital fluids
America’s booming blood-plasma industry
Paid-for plasma is both less exploitative than often recognised, and invaluable

"The World Health Organisation lists immunoglobulins and coagulation factors—both plasma-derived products—as essential medicines. Yet poor countries are often desperate for them and rich countries rely on American imports. Without financial incentives, supplies are hard to come by. “It’s not in people’s nature”, says Mr From, “to let a phlebotomist poke a needle in your arm and suck your blood out.”
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Vein attempts
Bans on paying for human blood distort a vital global market
The market in life-saving blood-plasma products depends on Americans who are paid for it

"The global demand for plasma is growing, and cannot be met through altruistic donations alone. Global plasma exports were worth $126bn in 2016—more than exports of aeroplanes. But paid plasma raises ethical, social and medical concerns: that it will lead to health catastrophes, as in the 1980s when tainted blood spread HIV and hepatitis; that it exploits the poor; and that it reduces the supply of “whole” blood, which is almost all donated voluntarily.

"None of these worries is well-founded. But Canadian reservations about paid plasma are shared across most of the world. America, China, parts of Canada and some European countries are among the few places that permit it. Those countries are extremely effective in securing supplies: three-quarters are collected in America alone, and another 10% in China, Germany, Hungary and Austria, where payment is also allowed. Of over 1,000 plasma-collection centres worldwide, 700 are in America. Jan Bult, head of a trade association representing companies that manufacture more than half of the world’s plasma products, says none collects plasma in countries that have banned compensation.

"Only countries that pay for plasma are self-sufficient in it. (Italy, where donors are given time off work, is close to self-sufficiency.) Half of America’s plasma is shipped to Europe—20m contributions-worth. Canada imports 80% of its plasma products from America. Australia imports 40% of its plasma products, too.

"Drug firms from countries that have banned pay-for-plasma do much of their collection in America. Three of the largest collection companies are European: Grifols of Spain, Shire of Ireland and Octapharma of Switzerland. The parent company of another big collector, CSL Behring, is Australian. Together these four firms run nearly eight out of ten plasma-collection centres. Some of their manufacturing capacity is in America, but much is located elsewhere. Switzerland, which collects very little plasma, exported $26bn-worth of plasma products in 2016.

...

It remains legal to pay for whole-blood donation in America today. But hospitals refuse to accept it. Today’s plasma, however, is safe from the contamination risks of the past. Modern screening and sanitisation are extremely effective. Graham Sher, chief executive of Canadian Blood Services, a non-profit, says plasma products from paid donors are “as safe as those from our unpaid donors”.

Other prejudices against pay-for-plasma are equally deep-seated. Some data, for example, lend weight to the suspicion that it preys on the poor. American plasma centres are concentrated in less well-off bits of the country. Typically they are in postal districts where 27.4% of the population are poor, according to The Economist’s analysis of census data. This is much higher than the average American poverty rate of 16.5%.

The other worry, shared by Dr Sher, is that paying for plasma may lead to a reduction in whole-blood donation. But, if that were true, the problem would be intensifying, as pay-for-plasma centres have nearly doubled worldwide in the past five years. But Peter Jaworski, of Georgetown University, is sceptical, suggesting that, anecdotes aside, the evidence shows paid plasma donation “does not crowd out voluntary blood-donation”. Americans, for example, continue to donate as much voluntary blood per head as do Canadians.

The aversion to paid-for plasma carries its own risks. According to Grifols, the geographic imbalance puts supplies of plasma products at risk. At the plasma industry’s main annual conference, held this year in Budapest in March, over-reliance on imports from America was a hot topic. Representatives from several countries (including Canada) recognised they must do more to diversify their supplies. Making it legal to pay for plasma is an obvious first step."

This article appeared in the International section of the print edition under the headline "Thicker than water"
 Print edition | International
May 10th 2018
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And here's a letter to the editor https://www.economist.com/letters/2018/06/02/letters-to-the-editor. (The highlighted sentence seems to reflect that the editor who decides what letters to publish is a different person than the economics editor  who writes that I study repugnance only to dismiss it, and whose views I remarked on here and here.)

"In your series of articles advocating for payments to plasma donors, you stress the positive supply effects that payments may have. Appeals to increased efficiency, however important, are unlikely to persuade politicians and the public when the opposition to payments resides in deep-rooted ethical concerns. Starting with the seminal work of Nobel laureate Alvin Roth, economists have begun to seriously consider how to design effective market mechanisms while respecting moral beliefs, in order to reach a virtuous balance in the trade-offs between morality and efficiency.

"Based also on our own research on ethically contentious transactions, we would suggest that policymakers collect two types of evidence before adopting extreme policies such as outright bans. First, pilot projects would help assessing the impact of various policy options. Second, policymakers should inform the public about this evidence, and take into account the ensuing prevailing opinions and ethical concerns in the population, instead of being based on pressures (in one direction or the other) from vocal but often scarcely representative groups.

NICOLA LACETERA
University of Toronto
MARIO MACIS
Johns Hopkins University
Baltimore, Maryland 

Peter Jaworski on The Case for Voluntary Remunerated Plasma Collections

Peter Jaworski makes the case for allowing compensation of plasma donors in the wealthy nations of the British Commonwealth:

Bloody Well Pay Them: The Case for Voluntary Remunerated Plasma Collections
BY PETER JAWORSKI JUNE 14, 2020

Here's the executive summary ( a long summary of a long paper):

"•Blood plasma is used in a wide, and growing, range of life-saving therapies. It is now being trialled to treat Covid-19, including by the United Kingdom’s National Health Service.

• There are significant global shortages of blood plasma. Demand is growing at a rate of 6-10% per year. Three-quarters of people do not have access to the appropriate plasma therapy, largely outside of developed countries.
• Shortages are significantly exacerbated by the World Health Organisation’s policy — adopted by the United Kingdom, Australia, New Zealand and some Canadian provinces — to rely exclusively on Voluntary Non-Remunerated Blood Donations (VNRBD).
• The United Kingdom imports 100% of its supply of blood plasma, Canada (84%), Australia (52%), and New Zealand (13%). They are increasingly dependent on imports for blood plasma from countries that remunerate donors. This inflates the global blood plasma price, making it unaffordable for low to middle income countries.
• The United States, which allows remuneration of donors, is responsible for 70% of the global supply of plasma. Together with other countries that permit a form of payment for plasma donations — including Germany, Austria, Hungary, and Czechia —they account for nearly 90% of the total supply. The dependence on a small number of countries is a serious health security threat.
• Non-remunerated donations are estimated to be 2-4 times more expensive than remunerated collections, because of the expense of recruiting and retaining donors, including through marketing. Australia, for example, could save $200 million annually by importing all blood plasma.
• There are significant global shortages of plasma therapies. The growing global demand cannot be met without remuneration.
• The evidence is clear that remunerating individuals for blood plasma donations is safe, would ensure a secure supply of plasma, does not discourage non-remunerated blood donations, and would provide significant patient benefits, including peace of mind.
• In order to ensure a safe, secure, and sufficient supply of plasma therapies, the United Kingdom, Canada, Australia, and New Zealand should adopt Voluntary Remunerated Plasma Collections (VRPC):
• VRPC means individuals are paid, in cash or in-kind, to give plasma of their own free will. It also means collections using modern deferral and testing techniques, such as deferring higher-risk donors and advanced viral detection tests.
• VRPC would allow the Canzuk countries to at the very least become self-sufficient, and potentially contribute to the humanitarian goal of increasing the global supply of blood plasma for low to middle income countries."

Here's a description of the historical setting:

"On June 11, 2009, the World Health Organization (WHO) issued “The Melbourne Declaration on 100% Voluntary Non-Remunerated Donation of Blood and Blood Components.”  The Declaration was a re-commitment to, what they call, “Voluntary Non-Remunerated Blood Donations” or VNRBD,” as well as to World Blood Donor Day, celebrated every June 14th.  The Declaration set a target date for achieving 100% VNRBD in safe, secure, and sufficient blood and blood products, including plasma-derived medicinal products. That target date was 2020.
...
"This year will end without a sufficient supply of plasma based on 100% non-remunerated plasma collections, neither will 2030. With each passing year from 2009 to the present, the world has moved further from that target, and closer to being nearly entirely dependent on the United States."

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Before publishing the paper, Jaworski solicited some supportive quotes to use as blurbs.  Here's mine:

Nobel Prize winning economist Alvin Roth says of the current over-reliance on the US’ paid donor market:
“I find confusing the position of some countries that compensating domestic plasma donors is immoral, but filling the resulting shortage by purchasing plasma from the U.S. is ok.”

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.

How to End the Plasma Shortage for Coranavirus Patients

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.

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

Commercial plasma collection in the US: the Jaworski report for 2025

 Peter Jaworski, a tireless student of blood donation around the world, has published a report on the plasma industry.  It's full of interesting facts, a few of which are highlighted below.

America’s Plasma Contribution to the World: 2025
Launching the Georgetown Blood and Plasma Research Group and the annual state of the U.S. plasma industry report  by Peter Jaworski 

"I am proud to announce the official launch of the Georgetown Blood and Plasma Research Group. Housed at Georgetown University, this initiative will serve as a dedicated academic hub for research on the ethics and economics of global supply chains for not only blood plasma, but blood, bone marrow, and other medically-useful substances of human origin. Our goal is to provide data-driven insights, foster serious philosophical discussion, and be a home for interdisciplinary research.
 

"This 2025 Annual Report is the first contribution to that mission. 

...

"As of December 31, there are 1,247 plasma collection centers in the United States (including four centers in Puerto Rico).

"To put this into perspective: The U.S. is now home to more plasma centers than community colleges (just over 1,000) or Kohl’s department stores (around 1,175). There are almost as many plasma collection centers as Denny’s restaurants (around 1,300). 

...

"we can look at the economics of independent plasma companies. Their business is to sell plasma to fractionators, not to make medicine from the plasma.

"The current selling price of a liter of plasma is around $190, give or take $10.

• Donors receive between 30-40% of that revenue, or around $70 (an average donation is 850 - 880 mL, requiring more than one donation to equal a liter).
• The center spends a majority of the remaining revenue on costs like employees, supplies (“softgoods”), testing, and facility overhead.
• The plasma center will pocket around 8-12%, or around $15 in profit. 

...

"The U.S. plasma industry does more than save American lives, it provides the material for life-saving therapies for patients around the world.

"The 62.5 million liters collected in the U.S. in 2025 represents around 68% of global plasma collections for the manufacture of medicines. About 52% of those collections will end up in medicines to treat American patients, while the remaining 48% will end up treating patients in the rest of the world."

Buying and selling blood plasma, with focus on Canada, continued

Peter Jaworski writes:

"I had a video with Big Think come out recently where I defend paying for plasma against a number of objections. It’s a bit on the long side (17 minutes), but I thought you might be interested in posting it to your blog: https://bigthink.com/videos/paid-plasma-ethics

"I also had an opinion piece on the same topic published in the National Post (with Kate Vander Meer, who is a patient that used plasma therapies): https://nationalpost.com/opinion/opinion-on-covid-19-canada-needs-to-pay-plasma-donors-to-protect-its-domestic-supply?video_autoplay=true"

From the video transcript:

"Out of all the countries in the world only the ones that pay people to make that donation are self-sufficient in plasma therapies. And even the ones that pay not all of them are, in fact, sufficient. So there are only seven countries in the world that legally permit paying people for plasma donations – Germany, Austria, Hungary, Czechia or the Czech Republic, parts of Canada. And I'll talk about Canada in a second. The United States, of course, and China. Those are the seven countries in the world that permit payment. Every other country that does not allow payment for plasma donations imports plasma therapies that make use of plasma primarily from Americans. Germans as well, but primarily Americans. "
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And here's the op-ed:

Opinion on COVID-19: Canada needs to pay plasma donors to protect its domestic supply
Kate Vander Meer and Peter Jaworski: In order to ensure that enough people are willing to give plasma to meet the ever-expanding need, we must urgently adopt a pay-for-plasma model here at home

"There’s no evidence that anything other than paying for plasma will work. According to an expert panel formed by Health Canada in 2018, paid donors in countries that permit payment are responsible for providing 89 per cent of the plasma used to make therapies, with the United States alone providing 70 per cent of the global supply. The panel also revealed that no country in the world that forbids paid donations collects enough plasma to meet its needs — not one!"

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."
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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

Plasma shortage alert from the IDF--the Immune Deficiency Foundation

The EU proposes strengthening bans on compensating donors of Substances of Human Origin (SoHOs)--op-ed in VoxEU by Ockenfels and Roth

 The EU has proposed a strengthening of European prohibitions against compensating donors of "substances of human origin" (SoHOs).  Here's an op-ed in VoxEU considering how that might effect their supply.

Consequences of unpaid blood plasma donations, by Axel Ockenfels and  Alvin Roth / 4 Nov 2023

"The European Commission is considering new ways to regulate the ‘substances of human origin’ – including blood, plasma, and cells – used in medical procedures from transfusions and transplants to assisted reproduction. This column argues that such legislation jeopardises the interests of both donors and recipients. While sympathetic to the intentions behind the proposals – which aim to ensure that donations are voluntary and to protect financially disadvantaged donors – the authors believe such rules overlook the effects on donors, on the supply of such substances, and on the health of those who need them.

"Largely unnoticed by the general public, the European Commission and the European Parliament’s Health Committee have been drafting new rules to regulate the use of ‘substances of human origin’ (SoHO), such as blood, plasma, and cells (Iraola 2023, European Parliament 2023). These substances are used in life-saving medical procedures ranging from transfusions and transplants to assisted reproduction. Central to this legislative initiative is the proposal to ban financial incentives for donors and to limit compensation to covering the actual costs incurred during the donation process. The goal is to ensure that donations are voluntary and altruistic. The initiative aims to protect the financially disadvantaged from undue pressure and prevent potential misrepresentation of medical histories due to financial incentives. While the intention is noble, the proposal warrants critical analysis as it may overlook the detrimental effects on donors themselves, on the overall supply of SoHOs, and consequently on the health, wellbeing, and even the lives of those who need them. We illustrate this in the context of blood plasma donation.

"Over half a century ago, Richard Titmuss (1971) conjectured that financial incentives to donate blood could compromise the safety and overall supply. This made sense in the 1970s, when tests for pathogens in the blood supply were not yet developed. But Titmuss’ conjecture permeated policy guidelines worldwide, despite mounting evidence to the contrary. Although more evidence is needed, a review published by Science (Lacetera et al. 2013; see also Macis and Lacetera 2008, Bowles 2016), which looked at the evidence available more than 40 years after Titmuss’ conjecture, concluded that the statistically sound, field-based evidence from large, representative samples is largely inconsistent with his predictions.

"Getting the facts right is important because, at least where blood plasma is concerned, the volunteer system has failed to meet demand (Slonim et al. 2014). There is a severe and growing global shortage of blood plasma. While many countries are unwilling to pay donors at home, they are willing to pay for blood plasma obtained from donors abroad. The US, which allows payment to plasma donors, is responsible for 70% of the world’s plasma supply and is also a major supplier to the EU, which must import about 40% of its total plasma needs. Together with other countries that allow some form of payment for plasma donations – including EU member states Germany, Austria, Hungary, and the Czech Republic – they account for nearly 90% of the total supply (Jaworski 2020, 2023). Based on what we know from controlled studies and from experiences with previous policy changes, a ban on paid donation in the EU will reduce the amount of plasma supplied from EU members, prompting further attempts to circumvent the regulation by importing even more plasma from countries where payment is legal. At the same time, a ban will contribute to the global shortage of plasma, further driving up the price and making it increasingly unaffordable for low-income countries (Asamoah-Akuoko et al. 2023). In the 1970s, it may have been reasonable to worry that encouraging paid donation would lead to a flow of blood plasma from poor nations to rich ones. That is not what we are in fact seeing. Instead, plasma supplies from the US and Europe save lives around the world.

"In other areas, society generally recognises the need for fair compensation for services provided, especially when they involve discomfort or risk. After all, it is no fun having someone stick a needle in your arm to extract blood. This consensus cuts across a range of services and professions – including nursing, firefighting, and mining – occupations, most people would agree, that should be well rewarded for the risk involved and value to society. To rely solely on altruism in such areas would be exploitative and would eventually lead to a collapse in provision. Indeed, to protect individuals from exploitation, labour laws around the world have introduced minimum compensation requirements rather than caps on earnings. In addition, payment bans on donors, even if they’re intended to protect against undue inducements, raise concerns about price-fixing to the benefit of non-donors in the blood plasma market. In a related case, limits on payment to egg donors have been successfully challenged in US courts. 1

"In addition, policy decisions affecting vital supplies such as blood plasma should be based on a broad discourse that includes diverse perspectives and motivations. Ethical judgements often differ, both among experts and between professionals and the general public, so communication is essential (e.g. Roth and Wang 2020, Ambuehl and Ockenfels 2017). Payment for blood plasma donations is an example. We (the authors of this article) are from the US and Germany, countries that currently allow payment for blood plasma donations while most other countries prohibit payment. On the other hand, prostitution is legal in Germany but surrogacy is not, while the opposite is true in most of the US. And while Germany currently prohibits kidney exchange on ethical grounds, other countries – including the US, the UK, and the Netherlands – operate some of the largest kidney exchanges in the world and promote kidney exchange on ethical grounds.

"The general public does not always share the sentiments that health professionals find important (e.g. Lacetera et al. 2016). This tendency is probably not due to professionals being less cognitively biased. In all areas where the question has been studied, experts such as financial advisers, CEOs, elected politicians, economists, philosophers, and doctors are just as susceptible to cognitive bias as ordinary citizens (e.g. Ambuehl et al. 2021, 2023). Recognising the similarities and differences between professional and popular judgements, and how ethical judgements are affected by geography, time, and context, allows for a more constructive and effective search for the best policy options.

"In our view, the dangers of undersupply of critical medical substances, of inequitable compensation (particularly for financially disadvantaged donors), and of circumvention of regulation by sourcing these substances from other countries (where the EU has no influence on the rules for monitoring compensation to protect donors from harm) are at least as significant as those arising from overpayment. Carefully designed transactional mechanisms may also help to respect ethical boundaries while ensuring adequate supply. Advances in medical and communication technologies, such as viral detection tests, can effectively monitor blood quality and ensure the safety and integrity of the entire donation process – including the deferral of high-risk donors and those for whom donating is a risk to their health – without prohibiting payment to donors. Even if it is ultimately decided that payments should be banned, there are innovations in the rules governing blood donation that have been proposed, implemented, and tested that would improve the balance between blood supply and demand within the constraints of volunteerism; non-price signals, for instance, can work within current social and ethical constraints.

"As the EU deliberates on this legislation, it is imperative to adopt a balanced, empirically sound, and research-backed approach that considers multiple effects and promotes policies to safeguard the interests of both donors and recipients.

References

Asamoah-Akuoko, L et al. (2023), “The status of blood supply in sub-Saharan Africa: barriers and health impact”, The Lancet 402(10398): 274–76.

Ambuehl, S and A Ockenfels (2017), “The ethics of incentivizing the uninformed: A vignette study”, American Economic Review Papers & Proceedings 107(5), 91–95.

Ambuehl, S, A Ockenfels and A E Roth (2020), “Payment in challenge studies from an economics perspective”, Journal of Medical Ethics 46(12): 831–32.

Ambuehl, S, S Blesse, P Doerrenberg, C Feldhaus and A Ockenfels (2023), “Politicians’ social welfare criteria: An experiment with German legislators”, University of Cologne, working paper.

Ambuehl, S, D Bernheim and A Ockenfels (2021), “What motivates paternalism? An experimental study”, American Economic Review 111(3): 787–830.

Bowles S (2016), “Moral sentiments and material interests: When economic incentives crowd in social preferences”, VoxEU.org, 26 May.

European Parliament (2023), “Donations and treatments: new safety rules for substances of human origin”, press release, 12 September.

Iraola, M (2023), “EU Parliament approves text on donation of substances of human origin”, Euractiv, 12 September.

Jaworski, P (2020), “Bloody well pay them. The case for Voluntary Remunerated Plasma Collections”, Niskanen Center.

Jaworski, P (2023), “The E.U. Doesn’t Want People To Sell Their Plasma, and It Doesn’t Care How Many Patients That Hurts”, Reason, 20 September.

Lacetera, N, M Macis and R Slonim (2013), “Economic rewards to motivate blood donation”, Science 340(6135): 927–28.

Lacetera, N, M Macis and J Elias (2016), “Understanding moral repugnance: The case of the US market for kidney transplantation”, VoxEU.org, 15 October.

Macis M and N Lacetera (2008), “Incentives for altruism? The case of blood donations”, VoxEU.org, 4 November.

Roth, A E (2007), “Repugnance as a constraint on markets”, Journal of Economic Perspectives 21(3): 37–58.

Roth A E and S W Wang (2020), “Popular repugnance contrasts with legal bans on controversial markets”, Proc Natl Acad Sci USA 117(33): 19792–8.

Slonim R, C Wang and E Garbarino (2014), “The Market for Blood”, Journal of Economic Perspectives 28(2): 177–96.

Titmuss, R M (1971), The Gift Relationship, London: Allen and Unwin.

Footnotes: 1. Kamakahi v. American Society for Reproductive Medicine, US District Court Northern District of California, Case 3:11-cv-01781-JCS, 2016.

Peter Jaworski on paid and unpaid plasma donation in Canada

Peter Jaworski in the Globe and Mail:
There’s a way to avoid blood plasma shortages: pay donors

and on the radio in Calgary (it isn't Peter in the picture:)


Some quotes from the Globe and Mail article:
" Canada collects only about 17 per cent of the plasma necessary to meet domestic demand for immune globulin. Paid donors in the United States are how we meet (and exceed) our country’s demand."

"Only countries that pay donors are self-sufficient in plasma. The rest have to import it from countries that pay. Paid donors in the United States are responsible for more than 60 per cent of the entire world’s plasma used to make plasma medicine."

"In terms of safety, a Health Canada Expert Panel report from May of last year noted that paid plasma is not less safe than unpaid plasma and it is less expensive than trying to recruit and retain unpaid donors. Paying donors is also the most likely way of ensuring security of supply. Paid donations having a negative effect on unpaid blood donations is also unlikely. The United States has more than 800 paid plasma centres, and still has higher blood donation rates than Canada."

"Claims that paid plasma exploits the poor are also mistaken. Pay is about $30 an hour in Canada (it takes 1.5 hours to donate plasma), and represents about 30 per cent of the total revenue from a litre of plasma (a much larger share than profits, which are less than 3 per cent of revenue). That’s a fair deal."

"Opponents also like to point out that plasma collected in the paid plasma centres in Canada is exported, with none of it staying in Canada. That’s true, but it’s true because Canadian Blood Services choose not to buy Canadian plasma in spite of its lower price and domestic origins."

How safe is plasma donation?

 Here's a story from the NYT, about the recent regularization of paid plasma donation in (some provinces of) Canada.

How Safe Is Plasma Donation?
Two recent deaths tied to for-profit clinics in Canada raised concerns about the health effects of having plasma drawn as often as twice a week. By Roni Caryn Rabin and Vjosa Isai

"Donating plasma, which is used to make lifesaving medicinal products, is widely perceived as low-risk. But questions about the safety of the practice arose this week when Canadian health authorities confirmed they were investigating two recent deaths of people who gave plasma at for-profit clinics in Winnipeg operated by Grifols, a Spanish health care company. 

"Millions of people donate frequently in North America. An estimated 60 to 70 percent of plasma-derived medicinal products worldwide are made from plasma donated in the United States.

And demand for plasma is growing. The market for plasma-derived medicinal products is valued at $40.35 billion and is expected to double over the next eight years, as the products are used to treat an expanding number of conditions, including immune deficiency syndromes and bleeding disorders.

But the health impact of frequent plasma donation on the donors themselves has not been well studied, and there is no consensus among health regulators about how long donors should wait between plasma draws.

In both Canada and the United States, companies can pay people an honorarium for donating their plasma, and health regulations say that people can donate up to twice a week.  

...

"A 2020 investigation by the F.D.A. into 34 deaths reported as being associated with plasma donation did not determine that donation was the cause of death in any of the cases. It ruled donation out entirely as a cause in 31 cases. "

 

The market for blood plasma: different tissues, same issues

I'll be speaking at The Plasma Protein Forum, June 12-13 in Washington D.C., on "REPUGNANT TRANSACTIONS AND FORBIDDEN MARKETS: DIFFERENT TISSUES, SAME ISSUES"

Here's the whole program:

DAY ONE:    JUNE 12, 2018

7:00 am–5:30 pm	Registration and Exhibit Hall Open
7:00–8:30 am	Breakfast—Available in Exhibit Halls 1 & 2
8:30–8:45 am	WELCOME & “How Is Your Day?”Jan M. Bult, President & CEO, PPTA
8:45–9:00 am	CHAIRMAN'S MESSAGE David Bell, Chair, PPTA Global Board of Directors; Executive Vice President & General Counsel, Grifols
9:00–10:30 am	PERSPECTIVES: ACCESS TO CARE Moderator:  Larisa Cervenakova, M.D., Ph.D., Medical Director, PPTA
	Speakers:  Tony Castaldo, President, US Hereditary Angioedema AssociationHAE perspective Joanna Chorostowska-Wynimko M.D., Ph.D., D.Sc., Professor, Scientific Director National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland Alpha-1 perspective Professor Paolo Caraceni, Associate Professor, Department of Medical and Surgical Sciences, University of Bologna, Bologna, ItalyANSWER: Long term albumin administration improves survival in patients with decompensated cirrhosis
10:30–11:00 am	BREAK
11:00 am–12:30 pm	CURRENT INDUSTRY AND REGULATORY INITIATIVES IN THE AREAS OF INSPECTIONS AND DONOR HEALTH Moderator:  John Delacourt, Vice President Legal Affairs & Global Operations, PPTA
	Speakers: Ginette Y. Michaud, M.D., Director, Office of Biological Products Operations, U.S. Food & Drug AdministrationFDA’s Office of Biological Products Operations – Form Follows Function Toby L. Simon, M.D., Senior Medical Director, Plasma & Plasma Safety, CSL PlasmaDonor health perspectives: Insights from industry plasma vigilance data and future safety initiatives George B. Schreiber, Sc.D., Director, Epidemiology, PPTA Iron depletion in Source plasma donors; A non sequitur.
12:30–2:00 pm	LUNCH—Buffet Available in Exhibit Halls 1 & 2    Sponsored by:
2:00–4:00 pm	INTERNATIONAL ACCESS TO CARE LANDSCAPE Moderator:  Jan M. Bult, President & CEO, PPTA
	Speakers: P. Martin van Hagen, M.D., Ph.D., Professor, Head, Clinical Immunology Unit Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands Is personalized medicine a national or cross border issue? Dr. Ranjeet S. Ajmani, CEO, PlasmaGen BioSciences Pvt Ltd. Initiatives to improve access to care in India Antonio Condino-Neto, M.D., Ph.D., President, Latin American Society for Immunodeficiencies (LASID)What needs to be done to improve access to Immunoglobulin therapy in Brazil? Diagnosis, Access, Supply
4:00 pm	BREAK – Ice cream social
4:30 pm	Otto Schwarz Award presentation
5:00 pm	REPUGNANT TRANSACTIONS AND FORBIDDEN MARKETS: DIFFERENT TISSUES, SAME ISSUES Alvin E. Roth, Craig and Susan McCaw Professor of Economics, Stanford University; George Gund Professor of Economics and Business Administration, Emeritus, Harvard University; and 2012 recipient of the Nobel Memorial Prize in Economic Sciences
5:45 pm	DAY 1 CLOSING ANNOUNCEMENTS
5:45–7:30 pm	Reception

DAY TWO:    JUNE 13, 2018

7:30 am–1:00 pm	Registration and Exhibit Hall open
7:30–8:30 am	Breakfast—Available in Exhibit Halls 1 & 2
8:30–8:35 am	WELCOME Joshua Penrod, J.D., Ph.D., Vice President, Source & International Affairs, PPTA
8:35–8:50 am	SOURCE DIVISION OUTLOOK Roger Brinser, ‎Chair, PPTA Source Board of Directors; Director, Regulatory, BioLife Plasma Services/Shire
8:50–11:00 am	CURRENT CHALLENGES  Moderator: Joshua Penrod, J.D., Ph.D., Vice President, Source & International Affairs, PPTA
	Speakers: Nicola Lacetera, Ph.D., Associate Professor at the University of Toronto Crowding Out Prof Dr. Liu Zhong, Vice President, Institute of Blood Transfusion, Chinese Academy of Medical Sciences (CAMS)Which is safer source plasma for manufacturing in China: apheresis plasma or recovered plasma? Chen Bin, Deputy Director, Medical Safety and Transfusion Division, Department of Medical Regulatory and Management, National Health CommissionThe current situation and challenge of the Chinese plasma management
11:00–11:30 am	BREAK
11:30 am–1:00 pm	CAN COUNTRIES DELIVER ON THEIR OWN? Moderator:  Julia Fabens, Senior Manager International Affairs, PPTA
	Speakers: Bill Bees, Vice President, Plasma Technologies, Prometic Plasma ResourcesCanada–Debunking the Krever Commission Report Peter Jaworski, Ph.D., Professor, Georgetown University, Washington, D.C. Ethics of Compensation Joshua Penrod, J.D., Ph.D., Vice President, Source & International Affairs, PPTAGlobal sufficiency: Obstacles and opportunities

***********
Here are my blog posts on plasma, sorted by date (most recent first), going back to one from 2009.

Plasma in Canada: payments and protests

 The local newspaper in Niagara on the Lake, a town in Ontario, Canada, covers the proposed opening next year of plasma collection centers that will pay for plasma.

Pay-for-plasma centre draws criticism from Health Coalition. The centre, which will pay residents to donate their blood plasma, is scheduled to open on Hespeler Road by early 2025, by Matt Betts

"The chair of the Waterloo Region Health Coalition is raising concerns about a pay-for-plasma centre slated to open on Hespeler Road in Cambridge by early 2025.

"Just as it sounds, residents can be compensated for donating their blood plasma.

"It's all part of an agreement between Spanish global healthcare company, Grifols, and the Canadian Blood Services.

"In September 2022, Canadian Blood Services announced our action plan in response to a global shortage of medications called immunoglobulins and plasma needed to make them," CBS said in an email to CambridgeToday.

"With funding from governments, Canadian Blood Services is opening 11 plasma donor centres in Canada and collecting more plasma ourselves. Our agreement with Grifols, a global healthcare company and leader in producing plasma medicines, is another part of that plan."

...

"paying for donations is banned in Ontario, Quebec and British Columbia. 

"However, CBS said its been in close discussions with the government and has an exemption.

...

"The agreement also complies with Ontario’s Voluntary Blood Donations Act, which has always contained an exemption for Canadian Blood Services, with implicit consideration of our agents, given our role as the national blood operator and supplier of blood products in Canada. Through our agreement, Grifols will operate under the Act as an agent of Canadian Blood Services."

"Per the agreement, Grifols must use plasma they collect in Canada to make immunoglobulins exclusively for patients in Canada, which reduces reliance on the global market, CBS said.

"But the whole operation doesn't sit right with Waterloo Region Health Coalition chair, Jim Stewart.

"It's a repugnant example of profit driven healthcare," Stewart said, questioning who's profiting in the end.

"What's next, paying people for their organs or embryos? This is just another example of Premier Doug Ford’s drive to privatize our healthcare system."

...

""These pay-for-donations centres really impact the homeless, people with low incomes and those with high levels of unemployment. This is going to dismantle the voluntary donor base and the sustainability of blood supply could be in jeopardy."

...

"While not confirmed by Grifols, Canadian Blood Resources and giveplasma.ca states qualified donors can earn up to $70 per donation and can donate twice in a seven day period."

#####

HT: Frank McCormick

Earlier:

Sunday, September 18, 2022

Canadian Blood Services to start paying Canadian plasma donors

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."

#####

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