Blood Money, by John Dooley and Emily Gallagher

 Are paid plasma donors being exploited? Here's a paper that suggests not, but rather that the payments that plasma donors receive can improve their financial well being not merely by providing additional income, but also by helping them avoid going into expensive debt.

 Dooley, John and  Emily Gallagher, Blood Money (October 11, 2021). Available at SSRN: https://ssrn.com/abstract=3940369 or http://dx.doi.org/10.2139/ssrn.3940369

Abstract: "Little is known about the motivations and outcomes of sellers in remunerated markets for human materials. We exploit dramatic growth in the number of commercial blood plasma centers in the U.S. to study the individuals who sell plasma. We find sellers tend to be young and liquidity constrained with low incomes and credit scores; they also report less access to traditional bank credit. Plasma centers absorb demand for non-traditional credit. The opening of a nearby plasma center reduces payday loan inquires and transactions by 13–18% among young borrowers. Meanwhile, foot traffic increases by over 9% at both essential and non-essential goods establishments when a new plasma center opens nearby. Our findings suggest that, at least in the short-term, constrained households use the discretionary income from plasma centers to smooth consumption without appealing to high-cost debt."

HT: Mario Macis

Canadian Blood Services to start paying Canadian plasma donors

 CBC news has the story, which seems to mark a turning point in a long struggle with repugnance for paying donors.

Canadian Blood Services signs agreement with private company to boost national plasma supply.  Some advocates calling for the resignation of Canadian Blood Services leaders over agreement. by Stephanie Dubois 

"Canadian Blood Services (CBS) is partnering with a private healthcare company to boost Canada's national blood plasma supply, the organization announced Wednesday.

...

"CBS has signed an agreement with Grifols, a company headquartered in Spain, which specializes in producing plasma medicines, the national blood collection organization said in a news release.

...

"Grifols will help CBS meet national targets for plasma supply by both collecting paid-for plasma and by turning Canadian plasma into immunoglobulins —a form of specialized medications called plasma protein products– for Canadian patients. 

...

"Health Canada says on its website there's currently "not enough plasma collected in Canada to meet the demand," and most of the plasma products distributed by CBS and Héma-Quebec are purchased from U.S. manufacturers and made from U.S. paid-donor plasma. "

Canadian Blood Services in talks around paid donations of plasma

Canadian Blood Services in talks around paid donations of plasma as supply dwindles. by Christopher Reynolds

"Canadian Blood Services is in talks with companies that pay donors for plasma as it faces a decrease in collections.

"The blood-collection agency issued a statement on Friday saying it is in “ongoing discussion with governments and the commercial plasma industry” on how to more than double domestic plasma collection to 50 per cent of supply.

"Canadian Blood Services has previously cautioned that letting companies trade cash for plasma - a practice banned in British Columbia, Ontario and Quebec - could funnel donors away from voluntary giving.

"The bulk of the non-profit agency's supply currently comes from abroad, including via organizations that pay donors."

HT: Frank McCormack

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

The Globe and Mail adds some detail:

Canadian Blood Services eyes getting plasma from paid donors amid supply challenges by Chris Hannay

"Industry observers say the most likely commercial partner for CBS is Grifols, an international pharmaceutical company headquartered in Spain. The company purchased a large-scale plasma processing facility in Montreal in 2020, and in January bought an existing for-profit plasma donation centre in Winnipeg.”

***********

See my full set of posts on plasma in Canada

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

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

 

Wednesday, May 20, 2020

Convalescent plasma collection and distribution

Plasma donations at the border

Here's a WSJ story about the confluence of two controversial transactions, immigration and compensation for plasma donors.

Block on Blood-Plasma Donors From Mexico Threatens Supplies. U.S. officials say crossing border to donate for a fee isn’t allowed with a visitor visa  By Mike Cherney,  Renée Onque and Daniela Hernandez

"Pharmaceutical companies and U.S. officials are fighting over whether to allow people to cross the border from Mexico to be paid for giving blood plasma, a critical ingredient in treatments for some neurological and autoimmune diseases.

"Up to 10% of plasma collected in the U.S. usually comes from Mexican nationals who enter on visitor visas and are paid about $50 to donate, according to legal filings from pharmaceutical companies. Last June, U.S. border officials indicated they would stop the roughly 30-year practice because they viewed it as labor for hire, which isn’t allowed under a visitor visa.

"The pharmaceutical companies that collect plasma have asked federal courts in Washington, D.C., to overturn the decision, which came just as U.S. plasma donations were disrupted by the Covid-19 pandemic. Some companies have argued that the payment compensates donors for their time and commitment rather than for the plasma itself, and isn’t in exchange for any actual work.

...

"The U.S., which provides much of the global plasma supply, is one of the few countries that allows payments to plasma donors, and supporters of the policy say that helps to ensure enough plasma is collected. Two big plasma companies, Australia-based CSL Ltd. and Spain-based Grifols SA, have invested millions of dollars in collection centers near the U.S.-Mexican border.

...

"A spokesperson for U.S. Customs and Border Protection declined to discuss the litigation.

...

"The agency said pharmaceutical companies could increase payments to attract more domestic supply and that Mexicans could still donate plasma without getting paid."

Blood donation, risk groups, and blood tests

 Before blood tests were developed for hepatitis virus and later for HIV, it made sense to screen potential blood donors by whether they were members of broad risk categories.  As tests have improved (and I think we still don't have those for prion based diseases like mad cow disease), it makes more sense to rely on testing, although risky behavior that might have recently resulted in infection, not yet detectable by blood tests, is still a screening factor.

All this is by way of saying that the current U.S. limitation on donation by homosexual men is out of date. Martha Gershun points me to this recent op-ed in the Baltimore Sun:

As a sexually active gay man, I can’t donate blood or tissue in America. That’s ridiculous | By GREG BRIGHTBILL

"My blood type is O negative, I am healthy, I can run a half-marathon, I do not smoke or use drugs, I only have two to three drinks a week, and I am in a committed relationship. Yet, due to homophobic stereotypes and outdated policies, gay men like myself  -- termed “MSM” or “men who have sex with men” -- cannot freely donate blood and soft tissue in America.

"According to the most recent Food and Drug Administration guidance, updated last year, MSMs must undertake a three-month deferral from male-to-male sexual activity before blood donation. Shockingly, that’s an improvement on the original full ban on blood donation implemented in 1985 (for any male who had a sexual encounter with another male after 1977) and the 2015 version of the policy, which required a 12-month deferral.

*********

In the UK, the guidelines have been changed, this month, to reflect the increased availability of testing. Here's the latest from the UK's NHS Blood and Transplant:

Landmark change to blood donation eligibility rules on today’s World Blood Donor Day  

"New eligibility rules that will allow more men who have sex with men to donate blood, platelets and plasma come into effect this week, marking an historic move to make blood donation more inclusive while keeping blood just as safe."

"From today (Monday) – World Blood Donor Day – the questions asked of everyone when they come to donate blood in England, Scotland and Wales will change. Eligibility will be based on individual circumstances surrounding health, travel and sexual behaviours evidenced to be at a higher risk of sexual infection.

"Donors will no longer be asked if they are a man who has had sex with another man, removing the element of assessment that is based on the previous population-based risks.

"Instead, any individual who attends to give blood - regardless of gender - will be asked if they have had sex and, if so, about recent sexual behaviours. Anyone who has had the same sexual partner for the last three months will be eligible to donate.

...

“We screen all donations for evidence of significant infections, which goes hand-in-hand with donor selection to maintain the safety of blood sent to hospitals. All donors will now be asked about sexual behaviours which might have increased their risk of infection, particularly recently acquired infections. This means some donors might not be eligible on the day but may be in the future."

...

"Under the changes people can donate if they have had the same sexual partner for the last three months, or if they have a new sexual partner with whom they have not had anal sex, and there is no known recent exposure to an STI or recent use of PrEP or PEP. This will mean more men who have sex with men will be eligible to donate.

"Anyone who has had anal sex with a new partner or with multiple partners in the last three months will be not be able to give blood right now but may be eligible in the future. Donors who have been recently treated for gonorrhoea will be deferred. Anyone who has ever received treatment for syphilis will not be able to give blood."

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."

***********

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.

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. "

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

Paying for plasma to be legal in Alberta

 Reason magazine has the story:

Canada Inches Closer to Allowing More People To Be Paid for Plasma--For too long, our northern neighbors have depended on plasma imported from the U.S. to meet demand. With the passage of new legislation in Alberta, this may change.  by LIZ WOLFE 

"Albertans will soon be able to receive payment for their blood and plasma donations. Bill 204, the Voluntary Blood Donations Repeal Act, was introduced by Tany Yao, a member of the legislative assembly for Alberta's provincial government, and passed in the legislature this week. It must now get royal assent—a mere formality—for it to become law. The bill overturns a 2017 prohibition on paid plasma, and will allow private companies to pay plasma donors for their efforts. If they so choose, people will still be able to donate blood and plasma without receiving compensation via Canadian Blood Services.

...

"United Nurses of Alberta's president Heather Smith told Global News that "the government is putting its ideology and desire to support profiteers above what is actually safe for Albertans and Canadians." Elsewhere she said that "donating blood should not be viewed as a business venture."

HT: Peter Jaworski

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

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

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

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

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

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

***********

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

Payment in challenge studies from an economics perspective 

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

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

An open letter to Canadian health authorities on laws against compensating Canadian plasma donors

 The letter is available on a website called Donation Ethics: Ethicists and Economists for Ethical Donation-Compensation Practices  organized by Peter M. Jaworski and  David Faraci. (I am among the signers.)

"Ethicists and Economists express concerns about banning compensation for plasma donors with regards to ensuring the security of a safe Immune Globulin Product Supply.

"Submission to the Expert Panel on Immune Globulin Product Supply and Related Impacts in Canada

"INTRODUCTION

We are professional ethicists in the fields of medical ethics, business ethics, and/or normative ethics, and academic economists who study how incentives and other mechanisms affect individual behaviour. We all share the goal of improving social welfare.

"The Provinces of Québec (1994),1 Ontario (2014),2 and Alberta (2017)3 have passed Voluntary Blood Donation Acts or their equivalents that prohibit, amongst other things, compensation for plasma donations for purposes of further processing into plasma-derived medicinal products (hereafter: “PDMPs”), like Immune Globulin (hereafter: “Ig”). Currently, the Nova Scotia legislature is debating a Voluntary Blood Donations Act,4 and the British Columbia government has suggested that it is interested in pursuing similar legislation.5

...

"CONCLUSION

"In our view, none of the moral objections to the compensatory model are persuasive. Furthermore, there is a strong moral presumption against standing in the way of a model that is the most likely to promote security not only of Canada’s supply of PDMPs, including Ig, but also of the global supply. We urge Québec, Ontario, and Alberta to reconsider the Acts currently prohibiting compensation in their provinces.

"Finally, we note that well-informed opponents of the compensatory model should not suggest that PDMPs, including Ig, made with compensated donors are riskier or less safe than PDMPs, including Ig, made with uncompensated donors. This presumption may be harmful to patients."

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."

Plasma in Canada, and repugnant transactions--a podcast interview

 I was recently interviewed by Kate van der Meer, a Canadian patient affected by the plasma shortage of 2019. Her experience inspired her to look deeper into the plasma supply chain and raise awareness to the negative implications of the Voluntary Blood Donations Act. Part of this awareness campaign is the Plasma For Life Podcast Series, of which this interview is a part. 

(Her website is  www.plasmaforlife.org.)

.

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:

Convalescent Plasma Reduced Death Rate Among Covid-19 Patients, Study Data Signals

Hospitalized patients who got earlier transfusions of blood plasma rich in antibodies to the coronavirus show a lower mortality rate

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

Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial

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.

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.)

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)

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."

*******

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.”

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"

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

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

Monday, May 18, 2020

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

Wednesday, May 20, 2020

Convalescent plasma collection and distribution