Saturday, May 30, 2020

Discussiong the pandemic with the Indian magazine Open

The Indian magazine Open published a brief interview with me, conducted by email:

‘Not only is wealth inequality rising, but the consequences of wealth inequality are also growing’

Here is the most interesting Q&A exchange:

"How concerned are you about the loss of jobs, especially in countries such as India where people in very low-income (informal) jobs are bearing the brunt of the lockdown? Is wealth inequality set to rise rapidly? ...
"In the near term I am very concerned by the loss of jobs. Not only is wealth inequality rising as a consequence, but also the consequences of wealth inequality are growing. Prosperous office workers can work remotely and be paid, but many manual workers can’t work remotely, and aren’t being paid."

Friday, May 29, 2020

Human Challenge Trials for COVID-19 vaccines

Yesterday I blogged about trying to speed up vaccine development and distribution by taking some of the risk out of it for pharma companies via an advanced market commitment, and today let's consider again one of the proposals being discussed  for speeding up the testing process.

Here's a white paper proposing some steps to further consider and prepare for human challenge trials (aka controlled human infection studies)  to speed up the testing of potential Covid-19 vaccines.It is put out by the organization 1 Day Sooner, which seeks to promote such trials, and has started assembling a list of volunteers in case challenge trials should become practical, to help vaccines become available sooner.

Evaluating use cases for human challenge trials in accelerating COVID-19 vaccine development
Linh Chi Nguyen , Christopher W Bakerlee, T. Greg McKelvey, Sophie M Rose, Alexander J Norman, Nicholas Joseph, David Manheim,, Michael R McLaren, Steven Jiang, Conor F Barnes, Megan Kinniment, Derek Foster, Thomas C Darton, Josh Morrison; for the 1Day Sooner Research Team

Abstract: Recently, human challenge trials (HCTs) have been proposed as a means to accelerate the development of an effective SARS-CoV-2 vaccine. In this paper, we discuss the potential role forsuch studies in the current COVID-19 pandemic. First, we present three scenarios in which HCTs could be useful: evaluating efficacy, converging on correlates of protection, and improving understanding of pathogenesis and the human immune response. We go on to outline the practical limitations of HCTs in these scenarios. We conclude that, while currently limited in their application, there are scenarios in which HCTs would be vastly beneficial and, thus, the option of using HCTs to accelerate COVID-19 vaccine development should be preserved. To this end, we recommend an immediate, coordinated effort by all stakeholders to (1) establish ethical and practical guidelines for the use of HCTs for COVID-19; (2) take the first steps toward an HCT, including preparing challenge virus under GMP and making preliminary logistical arrangements; and (3) commit to periodically re-evaluating the utility of HCTs amid the evolving pandemic.

Here's the main experimental design element:

"In HCTs, a relatively small number of healthy volunteer participants are administered a vaccine candidate or a placebo. However, unlike in conventional trials, consenting HCT participants are then administered an infectious dose of pathogen, and the outcomes of this infection is tracked. By challenging participants with pathogens under close observation in a clinical setting, HCTs can provide a unique opportunity to assess efficacy of a vaccine candidate."

And here are their concluding recommendations:

"To preserve the option to implement HCTs in scenarios such as this, we recommend an immediate, coordinated effort by all stakeholders to address the considerations outlined in this manuscript and make the necessary preparations. These include:
 1. Convening experts to discuss the ethical and practical considerations associated with HCTs for COVID-19, concluding in a set of  recommendations and guidelines for their use in the present pandemic and their role in the licensure process (which, notably, could provide guidance that is broadly useful in the event of future pandemics, too),
2. Taking the first practical steps toward an HCT, including preparing challenge virus under GMP and making preliminary arrangements with volunteers, vaccine developers, regulators, academic institutions, and clinical researchers to run HCTs in situations where they are expected to be highly useful,
3. Keeping informed of the evolving situation, periodically conducting a systematic reevaluation, and adjusting course based on the progress of the pandemic and the outcomes of the first drug and vaccine trials.

"HCTs have the potential to considerably shorten the COVID-19 pandemic, saving many lives and enabling economies and societies to return to normality. But we must act now to ensure this opportunity is not missed."

It's an admirably careful and balanced paper for one with a policy recommendation, and it sets the stage for a useful and timely debate.

As an experimenter,  I have one reservation about the proposed controls. In the passage I quoted above, they said " healthy volunteer participants are administered a vaccine candidate or a placebo," i.e. the control is a placebo.  That strikes me as potentially controversial given that the next step of the experiment is to infect the participants with Covid-19.  I might prefer a study in which the control for one vaccine was a different potential vaccine, so that no subjects were (relatively) sure to contract the disease.

But this doesn't detract from the usefulness of the preparations they recommend: conducting further discussions, and taking initial practical steps.
Here is my earlier post on this subject:

Friday, May 8, 2020 

Here's a similar in spirit paper, considering when and why human challenge trials might be appropriate, put out by the World Health Organization

Key criteria for the ethical acceptability of COVID-19 human challenge studies
WHO Working Group for Guidance on Human Challenge Studies in COVID-19
Authors:  WHO

"Overview: This document aims to provide guidance to scientists, research ethics committees, funders, policy-makers, and regulators in deliberations regarding SARS-CoV-2 challenge studies by outlining key criteria that would need to be satisfied in order for such studies to be ethically acceptable."

Here's a news story from CNN, complete with some anecdotes about the sometimes sketchy history of human challenge trials:

Thousands of people want to be exposed to Covid-19 for science
By Robert Kuznia

"Human challenge studies date all the way back to the first vaccine, for the highly lethal smallpox disease. The vaccine was developed in the late 18th century by physician Edward Jenner, who aimed to put a piece of folklore to the test: that milkmaids seemed to contract a milder form of the disease, called cowpox.
"In an experiment that today would warrant steep criminal charges, Jenner took pus from the scab of a milkmaid and inserted it into an incision on the arm of an 8-year-old boy. The child, James Phipps, developed a headache, chills and other mild symptoms, but when directly exposed to smallpox -- again through incisions on the arm -- he proved impervious."

Here's an op-ed from the Washington Post, by the philosophers Richard Yetter Chappell and Peter Singer:

Pandemic ethics: The case for experiments on human volunteers

They conclude:
"We are ethicists, not medical or biological scientists. When it comes to factual beliefs about the pandemic, we defer to expert scientific opinion, as everyone should. But what we ought to do with the facts we have, and how we should go about seeking facts we still lack, are ethical questions. Ethicists have a crucial role to play in this debate.

"There is too much that we don’t know about covid-19. The longer we take to find it out, the more lives will be lost. (That’s why the website asking for vaccine volunteers is called “1 Day Sooner.”) If healthy volunteers, fully informed about the risks, are willing to help fight the pandemic by aiding promising research, there are strong moral reasons to gratefully accept their help. To refuse it would implicitly subject others to still graver risks."

And here's a  post  from the Volokh Conspiracy (pointed out to me by Frank McCormick) focusing on the question of paying volunteers for human challenge trials:

The Moral Case for Testing Coronavirus Vaccines through "Challenge Trials" on Paid Healthy Volunteers
Doing so can potentially save many thousands of lives. And moral objections to this practice are weak. The issues here are very similar to the longstanding debate over whether we legalize organ markets.  by ILYA SOMIN .

He concludes:
"Like others who risk their lives to benefit others, challenge trial volunteers deserve our gratitude, and proper compensation for their efforts. And there is no good moral justification for forbidding them to take those risks. To the contrary, we should move ahead with challenge trials as soon as feasible. Every day of delay could literally be a matter of life and death—a great many lives and deaths."

Thursday, May 28, 2020

Advanced market commitment for a successful COVID-19 vaccine

Vaccines take a long time to develop and test, and so are risky for pharmaceutical firms to invest in. Here's a NY Times op-ed by several prominent economists suggesting that a market design solution, a government commitment in advance to support the market price of a successful vaccine, could be applied to speeding the development and widespread availability of a COVID-19 vaccine.

In the Race for a Coronavirus Vaccine, We Must Go Big. Really, Really Big.
We should commit tens of billions toward a program.
By Susan Athey, Michael Kremer, Christopher Snyder and Alex Tabarrok

"Vaccines often take 10 years to bring to market. We want a new vaccine as fast as possible, where each month matters.

The fact is that starting from the early stages of development, most vaccines fail. We cannot afford to fail, so we need to plan for success. To do that, we must think and invest as ambitiously as we can — and that means in a Covid vaccine advance market commitment.

The A.M.C. model was proposed in the early 2000s. And in 2007, the pneumococcus advance market commitment guaranteed vaccine manufacturers sales at a fixed price in return for an effective vaccine. It led to the successful development and distribution of hundreds of millions of doses of vaccine ...

"An advance market commitment for Covid-19 should combine “push” and “pull” incentives. The “pull” incentive is the commitment to buy 300 million courses of vaccine at a per-person price of $100, for vaccines produced within a specified time frame. If multiple vaccines are developed, the A.M.C. fund will have authority to choose products to purchase based on efficacy, the availability of sufficient vaccine for timely vaccination or suitability for different population groups. So firms compete to serve the first 300 million people with the most attractive vaccines, and the “pull” component provides strong incentives for both speed and quality.

"The “push” incentive guarantees firms partial reimbursement for production capacity built or repurposed at risk and partial reimbursement as they achieve milestones. The partial reimbursement ensures that manufacturers have “skin in the game,” while inducing them to build large-scale capacity before approval is certain."

Earlier post: Monday, March 16, 2020

Wednesday, May 27, 2020

Convalescent plasma collection ramps up

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

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

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

"So far nearly 15,000 seriously ill Covid-19 patients have received plasma transfusions in an emergency, expanded-access program authorized by the Food and Drug Administration
"The Red Cross has collected plasma from 4,000 recovered Covid-19 donors to date through its website, 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 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"

Tuesday, May 26, 2020

Incentive compatibility is not enough: evidence from the Israeli matching market for psychologists, by Hassidim, Romm and Shorrer

While it has taken some time for this paper to be published, I think it was the first to discover that some applicants in a labor market clearinghouse organized as an applicant proposing deferred acceptance algorithm were systematically misrepresenting their preferences, perhaps out of confusion. (This has since been observed in other markets as well.)  Their data are from the Israeli match for psychology graduate programs, which the authors also designed and organized.

Online early in Management Science:

The Limits of Incentives in Economic Matching Procedures
Avinatan Hassidim, Assaf Romm, Ran I. Shorrer
Published Online:13 May 2020

Abstract: Organizations often require agents’ private information to achieve critical goals such as efficiency or revenue maximization, but frequently it is not in the agents’ best interest to reveal this information. Strategy-proof mechanisms give agents incentives to truthfully report their private information. In the context of matching markets, they eliminate agents’ incentives to misrepresent their preferences. We present direct field evidence of preference misrepresentation under the strategy-proof deferred acceptance in a high-stakes matching environment. We show that applicants to graduate programs in psychology in Israel often report that they prefer to avoid receiving funding, even though the mechanism preserves privacy and funding comes with no strings attached and constitutes a positive signal of ability. Surveys indicate that other kinds of preference misrepresentation are also prevalent. Preference misrepresentation in the field is associated with weaker applicants. Our findings have important implications for practitioners designing matching procedures and for researchers who study them.

Monday, May 25, 2020

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

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

Sunday, May 24, 2020

Olly Williamson (1932-2020)

The great student of transaction costs, Oliver (Olly) Williamson, has died.

Here's the Berkeley obit:
Nobel laureate Oliver Williamson, pioneer of organizational economics, dies at 87

"His multidisciplinary approach to analyzing organizational structures was unconventional in economics at the time—he described it as a melding of soft social science with abstract economic theory. He looked not only at formal firm structure but at culture and social norms. Prof. Ernesto Dal Bó, the Phillips Girgich Professor of Business, called Williamson’s work “a fountain of vocation-shaping epiphanies.”

“After reading his work, we could no longer think of markets, organizations, and legal or political institutions in the same way. And so we didn’t,” Dal Bó said. “His insights are now part of the common sense of social scientists.”
He won the Nobel prize in economics in 2009: here's his autobiographical statement on the Nobel site. I was struck by this paragraph:

"Although I would not come to appreciate this last until later, there was a major difference between engineering and economics with respect to hypothetical ideals. Thus whereas assumptions of weightlessness or perfect gas laws or frictionlessness etc. served the purpose of simplification in engineering, these assumptions would give way to realities (in the form of friction, resistance, turbulence, and the like) as engineering applications were attempted. In economics, however, assumptions of frictionlessness (of which the standard assumption of zero transaction costs was one) often went unquestioned or, even worse, were invoked asymmetrically. Thus whereas markets were subject to “failures” for which corrective public policy measures were prescribed, there was no corresponding provision for failures in the public sector. A more symmetrical approach would be to recognize that positive transaction costs were the economic counterpart of friction and that all forms of organization experience such costs – albeit in variable degree (depending on the attributes of the transaction to be organized). I credit my engineering background with giving me a receptive attitude toward transaction costs, to include an interest in pinning down and working out the organizational ramifications of such costs."