Results for “blood plasma”
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Alex Armlovich on blood plasma donors and markets

From my email:

I saw your post about COVID blood brokers–My girlfriend and I had it in March and finally got antibody tests last week when the city opened the free clinics.

I inquired on a national plasma donor site, was directed to CSL Plasma in Clifton NJ, and a donor concierge from LeapCure reached out. They didn’t tell me what the compensation is (the CSL website says it’s usually ~$50 for normal plasma) but they’re calling a roundtrip Uber from my apartment near Ridgewood, Queens all the way to NJ, which is $108 one-way. The concierge said to reach out if there are any concerns with the first trip next week because they’re hoping for up to 2x weekly donations.

What I don’t understand is, why doesn’t the city’s antibody testing program directly link up to plasma donation? I had to go through a bunch of hassle to find out where to donate, and I think the information & coordination friction is a bigger deterrent than anything else. And why isn’t there more collection capacity in the city itself; the long commute seems unnecessary. If this is scientifically important enough to merit real donor spending from biotech, it seems like the city should make even a minimal investment in reducing process friction.

Maybe an integrated, frictionless testing & plasma donation infrastructure should be a permanent strategy for future “zero-day viruses” where convalescent antibodies are the only thing we have to treat first responders…

Here is Alex Armlovich on Twitter.

Dear Canada: Don’t Ban Paid Blood Plasma Donation

The United States has been called the OPEC of blood plasma because it exports hundreds of millions of dollars worth to other countries. Why does the US dominate the blood plasma industry? Because in the U.S. it’s legal to pay donors which increases supply. Some provinces in Canada have also allowed paid donors but 80% of the blood plasma given to Canadians is imported from the United States and, to make matters worse, some provinces have banned or are considering banning paid donation. A very good letter opposes the ban:

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.

We have strong reservations regarding any Act or legislation (hereafter: “Acts”) that would prohibit compensation for blood plasma donations…….Both the ethical and the economic arguments against a compensatory model for blood plasma for further manufacture into PDMPs are weak. Moreover, significant ethical considerations speak in favour of the compensatory model, and therefore against the Acts.

The letter carefully discusses many of the objections such as that paid donations will drive out unpaid:

The compensatory model leaves open the possibility of donors’ opting out of compensation, or the operation of a parallel non-compensatory model. The United States does just this, and has an approximately 50% higher voluntary, unpaid, per capita blood donation rate than Canada. Germany, Austria, and the Czech Republic, where plasma donors can be compensated, likewise all have higher rates of voluntary, unpaid per capita blood donation than Canada.

Is paid blood plasma less safe?

Dr. Graham Sher, the CEO of Canadian Blood Services, has said, “It is categorically untrue to say, in 2015 or 2016, that plasma-protein products from paid donors are less safe or unsafe. They are not. They are as safe as the products that are manufactured from our unremunerated or unpaid donors.”

The letter is signed by two Nobel Prize winners in economics, Alvin Roth and Vernon Smith, by philosophers like Peter Jaworski, who did most of the heavy lifting, and by experts who have studied incentives and blood donation closely like Nicola Lacetera and Mario Macis. I am also a signatory.

Bloody Well Pay Them

The United States is one of the few countries in the world where plasma donors are paid and it is responsible for 70% of the global supply of plasma. If you add in the other countries that allow donors to be paid, including Germany, Austria, Hungary, and Czechia, the paid-donor countries account for nearly 90% of the total supply.

Countries that follow the WHOs guidance to rely exclusively on voluntary, unpaid donors all have shortages of plasma (hmmm…what’s the WHOs track record like?) So what do these countries do? Import plasma from the paid-donor countries. The United Kingdom, Australia, New Zealand and some Canadian provinces, for example, prohibit paid donors and they import a majority of their plasma from paid donor countries. (See chart at right).

As Nobel prize winner Al Roth puts it, in his gentle way:

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 US is ok.

The UK, Australia, New Zealand and Canada can afford their moral hypocrisy but their decision to forbid paid-donors reduces the world supply of plasma driving up the price and harming people in poorer countries.

I have cribbed from an excellent new report by Peter Jaworski, Bloody Well Pay Them: The Case for Voluntary Remunerated Plasma Collections.

Previous MR posts on plasma.

Incentivizing Plasma Donation for Convalescent Therapy

Kominers, Pathak, Sonmez, and Unver apply market design tools to incentivize convalescent therapy:

COVID-19 convalescent plasma (CCP) therapy is currently a leading treatment for COVID-19. 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.

The idea is quite similar to the “no give, no take” rule for organ donation that I have promoted for many years. Namely, if you don’t sign your organ donor card you go to the back of the queue should you ever need an organ donation. Israel adopted the idea some years ago by giving points to people who signed their organ donor card. As with no-give, no-take, the point of the rules that Kominers et al. promote isn’t fairness per se but rather as an incentive to increase donations and thus increase the supply of plasma.

New York Will Try Convalescent Blood Therapy

On March 17 I wrote:  “A simple and medically feasible strategy is available now for treating COVID-19 patients, transfuse blood plasma from recovered patients.” New York, with other states following closely behind, is now trying the idea.

NBC News: Hoping to stem the toll of the state’s surging coronavirus outbreak, New York health officials plan to begin collecting plasma from people who have recovered and injecting the antibody-rich fluid into patients still fighting the virus.

Gov. Andrew Cuomo announced the plans during a news briefing Monday. The treatment, known as convalescent plasma, dates back centuries and was used during the flu epidemic of 1918 — in an era before modern vaccines and antiviral drugs.

Some experts say the treatment, although somewhat primitive, might be the best hope for combating the coronavirus until more sophisticated therapies can be developed, which could take several months.

The FDA acted quickly to approve the therapy on an emergency case-by-case basis, although it’s not clear to me that legally they should be involved at all given the therapy seems more like an off-label use of blood plasma than a new drug.

Convalescent Blood Therapy

A simple and medically feasible strategy is available now for treating COVID-19 patients, transfuse blood plasma from recovered patients. The idea is that the antibodies from the recovered patients will help the infected patients. The idea is an old one and has been used before with some success. Here is Robert Kruse from Johns Hopkins (who also makes other suggestions):

A simple but potentially very effective tool that can be used in infectious outbreaks is to use the serum of patients who have recovered from the virus to treat patients who contract the virus in the future. Patients with resolved viral infection will develop a polyclonal antibody immune response to different viral antigens of 2019-nCoV. Some of these polyclonal anti-bodies will likely neutralize the virus and prevent new rounds of infection, and the patients with resolved infection should produce 2019-nCoV antibodies in high titer.Patients with resolved cases of 2019-nCoV can simply donate plasma, and then this plasma can be transfused into infected patients. Given that plasma donation is well established, and the transfusion of plasma is also routine medical care, this proposal does not need any new science or medical approvals in order to be put into place. Indeed, the same rationale was used in the treatment of several Ebola patients with convalescent serum during the outbreak in 2014–2015, including two American healthcare workers who became infected.

As the outbreak continues, more patients who survived infection will become available to serve as donors to make antisera for 2019-nCoV, and a sizeable stock of antisera could be developed to serve as a treatment for the sickest patients.

Kruse worries that the exponential growth of the pandemic will be too fast but I think he makes a mistake. The number of recovered patients will far exceed the number of hospitalized patients so the supply of plasma will rise more quickly than the demand.

Convalescent blood therapy was used to treat people during the 1918 flu pandemic and appeared to be useful (see here for references to papers from that time.) A recent meta-analysis of patients treated with blood therapy during the 1918 flu found good results (noting, of course, that data from a hundred years ago wasn’t ideal) :

Patients with Spanish influenza pneumonia who received influenza-convalescent human blood products may have experienced a clinically important reduction in the risk for death. Convalescent human H5N1 plasma could be an effective, timely, and widely available treatment that should be studied in clinical trials.

Blood therapy has also been used periodically since that time to treat Ebola patients, MERS patients, Junin patients and others but under non-ideal conditions where lots of things were being tried at the same time and controls were not ideal. Results have been mostly positive or non-negative, e.g. this study on 84 Ebola patients found few benefits but also small costs. Blood therapy has also been used for animals.

To implement we need a database of recovered patients. The recovered patients then needed to be tested to find those with the most antibodies. It is probably best to use recovered patients from the same location to maximize overlap although the Chinese brought plasma from China to Italy. Most of the dangers from blood transfusion such as passing on another disease are well understood and should be manageable with testing and knowledge of donors. In rare cases such as Dengue it can bad to stimulate the immune system (see discussion here).

Plasma therapy is not difficult and there are firms with expertise in the field including Takeda and Regenernon the latter of whom developed a blood based treatment for Ebola. Thus, CBP seems worthy of consideration.

Hat tip: Monique van Hoek.

Money for Blood is Good for All

The Economist: For years [Barzin Bahardoust] has been trying to pay Canadians for their blood plasma—the viscous straw-coloured liquid in blood that has remarkable therapeutic powers. When his firm, Canadian Plasma Resources (CPR), tried to open clinics in Ontario in 2014, a campaign by local activists led to a ban by the provincial government on paid plasma collection. Undeterred, he tried another province, Alberta—which also banned the practice last year. Then, on April 26th, when CPR announced a planned centre in British Columbia, its government said it too was considering similar legislation. CPR has managed to open two centres, in far-flung Saskatchewan and New Brunswick. Even these have faced opposition.

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.

…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.

It’s a very odd “ethical policy” that leads Canadian provinces to ban paying Canadians for plasma but then import paid plasma from the United States. I am one of the signatories (along with Al Roth, Vernon Smith and Gerald Dworkin among others) of a letter that argues for the efficiency and ethics of allowing compensation for blood plasma donation. The Economist riffs of this letter in a very good op-ed:

The aversion to paid plasma rests on three reasonable-sounding but largely groundless propositions. The first is that it is unsafe. Payment might encourage donors to conceal dangerous behaviour—such as intravenous drug use. In the 1980s and 1990s, tainted blood products infected half the world’s haemophiliacs with HIV, along with tens of thousands of plasma donors in China. But modern plasma products do not carry such risks. They are heat-treated and bathed in chemicals to sanitise them (an impossibility for blood for transfusion). Since the adoption of these techniques there has not been a single case of transmission of HIV or hepatitis via plasma products. Doctors agree that plasma products from paid donors are just as safe as those from unpaid ones.

A second argument is that, if people are paid for their plasma, fewer will volunteer to donate whole blood for transfusions. (Paying for whole blood would be unwise, since it cannot be sterilised as plasma can.) But there is no evidence that paying for plasma diminishes the supply of donated blood. That is why, in Canada, more than 30 economists and philosophers wrote an open letter arguing against bans on paid plasma. Americans voluntarily donate as much blood per person as do Canadians.

A third argument is that paying for plasma preys on the poor. It is possible that those selling plasma need the money and therefore might give too often. In America plasma donors can give twice a week; those in Europe can give just once a week. There is no evidence of harm to their health in either case, but more long-term study would be prudent.

Those against allowing payment suggest using voluntary donors instead. Yet every country that does not pay ends up importing plasma. And the fact that America is by far the dominant supplier carries risks of its own. The dependence on a single source leaves the rest of the world vulnerable to an interruption of supply. To protect their people, therefore, other governments need to diversify their supplies of plasma. Paying for it would make a big difference.

Rewarding Altruism: Blood for Money

Do pecuniary incentives increase blood donation or do extrinsic incentives crowd out intrinsic incentives? In Rewarding Altruism (NBER, free) an important and impressive new paper Nicola Lacetera, Mario Macis and Robert Slonim analyze a field experiment involving some 100,000 donors and find that pecuniary incentives significantly increase blood donations. The field experiment covers a wide geographic area and the donors are tracked for a significant period of time after donating so the authors can look for geographic and temporal spillovers. The authors offered potential donors gift cards of $5, $10 and $15.

Subjects who were offered economic rewards to donate blood were more likely to donate, and more so the higher the value of the rewards. They were also more likely to attract others to donate, spatially alter the location of their donations towards the drives offering rewards, and modify their temporal donation schedule leading to a short-term reduction in donations immediately after the reward offer was removed. Although offering economic incentives, combining all of these effects, positively and significantly increased donations, ignoring individuals who took additional actions beyond donating to get others to donate would have led to an under-estimate of the total effect, whereas ignoring the spatial effect would have led to an over-estimate of the total effect.

Some of the increase in supply came from temporal substitution but this is not without value. Incentives are not just about increasing supply but also about increasing supply at the right time, i.e. when blood is most needed so it’s useful to have a lever that can influence when donations are made.

Crowding out did receive some support in an odd context. The authors found that donors who were surprised with a gift card after they had donated were less likely to donate in the future. Thus, the donors did not reciprocate the unexpected gift and may have felt that their altruistic intention was being undermined. Once again we see the overwhelming importance of context when trying to understand incentives. To paraphrase Mises, an incentive is not an objective fact but a subjective interpretation.

The authors did not find any decline in quality ala Titmuss. Indeed, this is to be expected since modern blood donation is not a random shout-out to people on the street but instead relies predominantly on repeat donors with a long donation history.

Gift cards of $5, $10 and $15 are small incentives and the authors suggest that the benefits from the increased supply far exceed the costs. It’s notable that it takes longer to donate blood plasma and as a result the U.S. blood plasma industry (the “OPEC of blood plasma”) has always relied on paid donors.

Here are my powerpoint slides on Incentives to Increase Organ Donation and here is an older post on sperm exports.

Our regulatory state is failing us, antibodies edition

It might be the next best thing to a coronavirus vaccine.

Scientists have devised a way to use the antibody-rich blood plasma of COVID-19 survivors for an upper-arm injection that they say could inoculate people against the virus for months.

Using technology that’s been proven effective in preventing other diseases such as hepatitis A, the injections would be administered to high-risk healthcare workers, nursing home patients, or even at public drive-through sites — potentially protecting millions of lives, the doctors and other experts say.

The two scientists who spearheaded the proposal — an 83-year-old shingles researcher and his counterpart, an HIV gene therapy expert — have garnered widespread support from leading blood and immunology specialists, including those at the center of the nation’s COVID-19 plasma research.

But the idea exists only on paper. Federal officials have twice rejected requests to discuss the proposal, and pharmaceutical companies — even acknowledging the likely efficacy of the plan — have declined to design or manufacture the shots, according to a Times investigation. The lack of interest in launching development of immunity shots comes amid heightened scrutiny of the federal government’s sluggish pandemic response.

Here is more from the LA Times, substantive throughout, via Anecdotal.

Canada Imports Precious Bodily Fluids

In 2004 Canada prohibited paying Canadian sperm donors, leading to a tremendous shortage as I had predicted in 2003 (see also my post, The Great Canadian Sperm Shortage). Canadian Peter Jaworski has an update (oddly enough published in USA Today):

Canada used to have a sufficient supply of domestic sperm donors. But in 2004, we passed the Assisted Human Reproduction Act, which made it illegal to compensate donors for their sperm. Shortly thereafter, the number of willing donors plummeted, and sperm donor clinics were shuttered. Now, there is basically just one sperm donor clinic in Canada, and 30-70 Canadian men who donate sperm. Since demand far outstrips supply, we turn to you. We import sperm from for-profit companies in the U.S., where compensating sperm donors is both legal and normal.

Note, by the way, that contrary to what you might expect from Titmuss et al. US sperm is considered to be of high quality because it comes with information about the donor.

And sperm isn’t the only precious bodily fluid that Canada imports.

Canada has never had enough domestic blood plasma for plasma-protein products, such as immune globulin. Our demand for those products, however, is increasing. Last year, we collected only enough blood plasma from unremunerated donors to manufacture 17% of the immune globulin demanded. The rest we imported from you, in exchange for $623 million, or $512 million U.S.

Reliance on your blood plasma looked like it might change a little bit when, in 2012, a company called Canadian Plasma Resources announced plans to open clinics in Ontario dedicated to collecting blood plasma. The trouble is that its business model included compensating donors. Almost immediately, groups such as the Canadian Union of Public Employees and the Canadian Health Coalition began to lobby the Ontario government to pass a law to stop CPR from opening clinics. Ontario obliged in 2014, passing the Safeguarding Health Care Integrity Act, which among other things made compensation illegal.

…As for safety, the fact that we import products made with remunerated donors should tell you that it is emphatically not an issue. Health Canada has said that there is no health concern. The CEO of Canadian Blood Services, Graham Sher, took to YouTube to explain that “it is categorically untrue to say, in 2015 or 2016, that plasma-protein products from paid donors are less safe or unsafe. They are not. They are as safe as the products that are manufactured from our non-remunerated or unpaid donors.”

As Jaworski writes:

What Canada should do is legalize compensation for renewable bodily fluids in our own country. It would be the morally right thing to do. It would help make and save more lives, without harming anybody.

Why Vampires Live So Long

NYTimes: Two teams of scientists published studies on Sunday showing that blood from young mice reverses aging in old mice, rejuvenating their muscles and brains. As ghoulish as the research may sound, experts said that it could lead to treatments for disorders like Alzheimer’s disease and heart disease.

wallpaper-true-blood-bottle-1600The key papers are here and here and here. Some of the papers are pointing to a specific protein but the last paper suggests that simple transfusions also work and that raises a number of issues of public policy. As Derek Lowe notes:

Since blood plasma is given uncounted thousands of times a day in every medical center in the country, this route should have a pretty easy time of it from the FDA. But I’d guess that Alkahest is still going to have to identify specific aging-related disease states for its trials, because aging, just by itself, has no regulatory framework for treatment, since it’s not considered a disease per se.

…You also have to wonder what something like this would do to the current model of blood donation and banking, if it turns out that plasma from an 18-year-old is worth a great deal more than plasma from a fifty-year-old. I hope that the folks at the Red Cross are keeping up with the literature.

US Sperm Exports Explode; Canadians Upset

The US is a world leader in sperm exports primarily because sperm banks in the U.S. are run on a for-profit basis. As a result, US sperm is reckoned to be of high quality (we always knew this didn’t we?) particulary because the US version comes with a background on the vitals of the donor. Denmark also exports a lot of sperm because of high standards and demand for that blond, blue-eyed look.

Exports to Canada have increased in recent years because of a scandal involving poorly screened Canadian sperm. Canadians also import a lot of US eggs. The Canadian government, however, is apparently miffed as a new law is being readied that would forbid donations involving a paid donor. The law would not only make paid donation illegal in Canada it would make it illegal to use any paid-for sperm. Canadian couples seeking fertility options will suffer and who will benefit? I cannot think that this law is anything but spiteful and ridiculous. Is paying for sperm an original sin? As with other areas of Canadian medicine (see Tyler’s posts here and here), the rich will now travel to the United States for treatment.

Aside: The Canadian Health Official quoted here is ignorant or disengeneous when she says “We don’t buy or sell blood, or organs or tissues.” In fact, Canada also imports a lot of US blood plasma. Plasma takes longer to donate than straight blood and as a result altruistic donation rates are low and much of the world relies on paid-for US plasma for its life-saving properties. Similarly, donating eggs is not nearly as much fun as donating sperm so altruistic donation of Canadian eggs is unlikely to make-up for restrictions on the import of paid-for US eggs.

Thanks to Eric Crampton for the seminal email.

Incentives for Organ Donation

Lottery tickets for vaccination seems to have been reasonably succesful. What else could we use incentives for? Al Roth sends us to kidney surgeon Arthur Matas’s argument for testing incentives for organ donation:

A regulated system of incentives for donation could provide a sizable increase in the number of kidneys available for transplant. Yet incentives for kidney donation are illegal in the US.
…Initially, the concept of incentives for living donation can be unsettling (some have said “repugnant”4). Yet ethicists worldwide have argued that there is no ethical reason to prohibit incentives. And studies show that the public is in favor of incentives. Additionally, dialysis is more expensive than transplant; a regulated system of incentives would be cost saving to the health care system.

We accept kidney donation. Any successful argument against incentivized donation must be able to differentiate it from our currently accepted conventional donation. Notably, incentives are legal for plasma, sperm, and egg donation or surrogate motherhood, and certainly there are risks involved with egg donation and surrogate motherhood. Gill and Sade5 argue that the only difference between donating and selling is monetary self-interest, and monetary self-interest alone does not warrant legal prohibition.

It is time to move past the feelings that incentives are wrong to the reality that as a result of a potentially preventable shortage of organs, patients on the waiting list are dying or becoming too sick to transplant….It is time for professional societies and patient groups to advocate for changing the law to allow trials of incentives for donation.

See many previous posts at MR on organ donation and blood donation.

Decentralized serological testing?

I would like to know more, but here is one new paper on the topic, by Lottie Brown, et.al.:

Serological testing is emerging as a powerful tool to progress our understanding of COVID-19 exposure, transmission and immune response. Large-scale testing is limited by the need for in-person blood collection by staff trained in venepuncture. Capillary blood self-sampling and postage to laboratories for analysis could provide a reliable alternative. Two-hundred and nine matched venous and capillary blood samples were obtained from thirty nine participants and analysed using a COVID-19 IgG ELISA to detect antibodies against SARS-CoV-2. Thirty seven out of thirty eight participants were able to self-collect an adequate sample of capillary blood (≥50 μl). Using plasma from venous blood collected in lithium heparin as the reference standard, matched capillary blood samples, collected in lithium heparin-treated tubes and on filter paper as dried blood spots, achieved a Cohen′s kappa coefficient of >0.88 (near-perfect agreement). Storage of capillary blood at room temperature for up to 7 days post sampling did not affect concordance. Our results indicate that capillary blood self-sampling is a reliable and feasible alternative to venepuncture for serological assessment in COVID-19.

Via Alan Goldhammer.

The shift of prevalance toward the young

Half of new coronavirus infections in Washington [state] are now occurring in people under the age of 40, a marked shift from earlier in the epidemic when more than two-thirds of those testing positive were in older age groups.

A new analysis finds that by early May, 39% of confirmed cases statewide were among people age 20 to 39, while those 19 and younger accounted for 11%.

Here is the full article, via Anecdotal.  A number of points:

1. As people adjust, and the higher-risk individuals take greater precautions, and the lower risk people relax their vigilance, this is likely to happen.

2. The case for age segregation, as a remedy and protection, becomes stronger.  If your policy prescriptions never change over the course of a pandemic, you are not paying sufficient attention, or you are a dogmatist, or both.

3. Universities have to worry a bit less about their students and a bit more about their faculty, at the margin.

4. As more young people acquire immunity, the incentive for yet additional young people to invest in immunity, through stochastic deliberate exposure, rises.  That in turn strengthens #2 and #3.

5. Will markets play a further role in this trend?  The excellent Kevin Lewis sends me the following (WSJ):

…while surging demand has proven a boon for the traders known as blood brokers who source this commodity, diagnostic companies say high prices for the blood of recovered Covid-19 patients are posing a hurdle to developing tests. ‘We’ve had a terrible time trying to obtain positive specimens at a decent rate,’ said Stefanie Lenart-Dallezotte, manager of business operations for San Diego-based Epitope Diagnostics Inc., which sells an antibody test for Covid-19…She said one broker quoted $1,000 for a one-milliliter sample of convalescent plasma, a term for the antibody-containing part of the blood from recovered patients. Executives at other diagnostics companies say they have been quoted prices of several thousand dollars for one milliliter of plasma.

What is the market-clearing price here, and what is the elasticity of exposure with respect to that price?  Evolving…

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