Showing posts with label vaccine. Show all posts
Showing posts with label vaccine. Show all posts

Tuesday, February 13, 2024

Incentives to take tests and get vaccinated

 As the pandemic phase of Covid-19 recedes, we can reflect on what we've learned about demand for tests and for vaccines.   Here's a paper from a year ago that I missed at the time  that discusses incentives and defaults.

Incentives and Defaults Can Increase COVID-19 Vaccine Intentions and Test Demand, by Marta Serra-Garcia and Nora Szech, Management Science, Vol. 69, No. 2, February 2023, Pages 723-1322, iii-iv

Abstract: Willingness to vaccinate and test are critical in the COVID-19 pandemic. We study the effects of two measures to increase the support of vaccination and testing: defaults and monetary compensations. Some organizations, such as restaurants, fire departments, hospitals, or governments in some countries, have used these measures. Yet there is the concern that compensations could erode intrinsic motivation and decrease vaccination intentions. We show that, in the early stages of the pandemic, both approaches, compensations and defaults, significantly increased COVID-19 test demand and vaccine intentions. Compensations for vaccines, however, need to be large enough because low compensations can backfire. We estimate heterogeneous treatment effects to document which groups are more likely to respond to these measures. The results show that defaults and avoidance of small compensations are especially important for individuals who are more skeptical of the vaccine, measured by their trust in the vaccine and their political views. Hence, both measures could be used in a targeted manner to achieve stronger results.

Tuesday, October 24, 2023

Scientists deliberately gave women Zika--challenge trials for diseases whose incidence has dropped too far for conventional clinical trials

 Nature has the story (despite the somewhat inflammatory headline).

Scientists deliberately gave women Zika — here’s why. ‘Human challenge’ results suggest that such trials could be used to test vaccines when Zika incidence is low.  by Mariana Lenharo, Nature, 21 October 2023

"For the first time, scientists have deliberately infected people with Zika virus to learn whether such a strategy could help to test vaccines against the pathogen.

The virus can cause severe birth abnormalities in babies born to parents infected during pregnancy. It also has been associated with neurological problems in adults, although those cases are rare. But infected study participants had only mild symptoms, and none became pregnant during or immediately after the trial. The results raise hopes that ‘human challenge’ programmes — in which volunteers are exposed to a pathogen in a controlled setting — could make it feasible to test vaccines at a time when Zika incidence is low.

“This is a great scientific gain in terms of the development of a vaccine,” said Rafael Franca, an immunologist at the Oswaldo Cruz Foundation in Ribeirão Preto, Brazil. The results are scheduled to be presented today at the annual meeting of the American Society of Tropical Medicine and Hygiene in Chicago, Illinois.

...

"In 2022, after a long process to address ethical concerns around the study, Durbin and her team recruited 28 healthy women, aged 18 to 40, who were neither pregnant nor lactating. All agreed to be admitted to a research facility and remain there until they were no longer infectious; they stayed at the unit for 9 to 16 days. They were tested for pregnancy several times before receiving the virus, to avoid the risk of congenital problems associated with Zika, and were counselled to use birth control for at least two months after the study.

Hope for smaller trials

The researchers injected 20 participants with one of two strains of Zika virus and eight with placebo. All of the participants who received the virus were infected; of those, 95% developed a rash — a common symptom of Zika — and 65% had joint pain. None of the placebo recipients had those symptoms.

Durbin says the findings indicate that the two strains of Zika administered in the trial can be safely and effectively used to infect participants in a Zika vaccine trial. She estimates that the controlled human infection model could be used in a phase III clinical trial for vaccine efficacy with as few as 50 to 100 participants. “With the challenge model, where you have 100% of infections, you could get an efficacy result with many fewer people” than in a conventional trial, says Durbin.

...

The new study represents a turnaround in the thinking about challenge trials. In early 2017, a report by researchers convened by the National Institute of Allergy and Infectious Diseases and the Walter Reed Army Institute of Research concluded that the risks of a human-infection study for Zika, at that time, surpassed the potential benefits.

...

But “from that time to now, we learnt a lot,” says Palacios. “Now we know that the risk of the virus being transmitted to another person through sexual relationships is limited and something that can be controlled,” he says. And regulators have signalled that they might consider data from human challenge trials in vaccine development, “in particular for those diseases that don’t have enough incidence to test in the field.”

Despite the low number of Zika cases, researchers say that it’s important to continue the efforts to develop a vaccine, because the virus might make a comeback. “Infections are much lower than they were during the epidemic in 2016. However, they are still occurring,” says Neil French, an infectious-disease specialist at the University of Liverpool, UK, who is involved in a Zika vaccine-development project. “The justification for a vaccine remains strong.”

Friday, September 22, 2023

Support for hepatitis C human challenge studies, in The Lancet Gastroenterology & Hepatology

 Here's a call for action, in The Lancet Gastroenterology & Hepatology:

Joint statement in support of hepatitis C human challenge studies by Harvey J Alter, Eleanor Barnes, Mia J Biondi, Andrea L Cox, Jake D Eberts, Jordan J Feld, T Jake Liang, Josh Morrison, Charles M Rice, Naglaa H Shoukry, David L Thomas, Jennifer Van Gennip, Charles Weijer, on behalf of other signatories †, Published:September 20, 2023 DOI:https://doi.org/10.1016/S2468-1253(23)00314-X

"We, the 121 undersigned, believe that human challenge studies among adult volunteers will be critical in the development of hepatitis C vaccines.

...

"Despite the advent of safe and highly effective direct-acting antiviral (DAA) treatments, the ongoing toll of hepatitis C remains high among low-income and middle-income countries and vulnerable populations such as people who inject drugs. Millions of new infections occur annually, outpacing cures in some regions,1 with progress further disrupted by the COVID-19 pandemic. Without a change in strategy and the development of new tools, we will not reach the ambitious goal set out by WHO of elimination of viral hepatitis as a public health threat by 2030. This will require an effective hepatitis C vaccine—“the best insurance for the future”, as highlighted by a recent announcement of the White House national hepatitis C elimination programme.2

...

"Human challenge studies for a hepatitis C vaccine could accelerate vaccine development dramatically. The effort to establish the model and test an initial vaccine candidate could take as little as 3 years. If that candidate fails, subsequent studies to test others could provide evidence of efficacy as quickly as 1 year.

"It is only because of the remarkably effective treatments that we can now consider human challenge studies for hepatitis C. With DAAs, cure rates of people without cirrhosis are reliably over 98%, with highly effective salvage regimens for the few who do not respond to a first course of therapy.5,  6 We are confident that in the era of DAAs, human challenge studies can be done in accordance with the highest ethical and safety standards. Healthy volunteers providing fully informed consent would be infected for at most 6 months before treatment and would be free to go about their lives with the right to request treatment and withdrawal from a study at any time. Acute infection causes no or few symptoms in most, and unlike in most challenge studies, where the risk of transmission necessitates quarantine of participants, the risk of passing hepatitis C to others is very low in day-to-day life.

"The impact of a vaccine would be enormous: reducing transmission, preventing cirrhosis, and most importantly, markedly reducing the rate of liver cancer, the world's second-most deadly cancer in terms of total fatalities.7 The global success of hepatitis B vaccine in achieving these goals exemplifies the importance of an effective hepatitis C vaccine. With the prospect of such a significant advance, we have confidence that people will volunteer to participate in hepatitis C challenge studies, and with such a strong team of experts worldwide, we are confident this approach will lead to the development of a successful hepatitis C vaccine."

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Here's the full list of 121 signers of the letter

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1Day Sooner has a related web page with some background: https://www.1daysooner.org/hepatitis-c-open-letter

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Earlier related posts:

Monday, May 15, 2023

Monday, September 4, 2023

Covid medication: allocation, information, hesitancy, and uptake: what are some things we have learned?

 I've posted before about how informational advertising about vaccine availability and safety seems to have had a positive effect on vaccination rates among disadvantaged populations. There was particular concern in the U.S. at one point that Black people were less likely to receive vaccines and other medications than other Americans.

Today's post collects several papers about the effect of randomly allocating invitations for temporarily scarce Covid medications, while giving members of disadvantaged groups a higher probability of receiving an invitation.  Included will be an editorial warning us that we shouldn't be satisfied to judge the outcome of a market design by its intended outcome ("Moving Beyond Intent and Realizing Health Equity").

There are market design lessons in these last few years of Covid experience that I hope will help make the responses to future pandemics more effective. Not least of these is that the allocation of public health  and medical resources turns out to be quite different from  the allocation of other kinds of resources, in many important ways that reflect the broader economic and social environments in which different kinds of allocation takes place.

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Here's a paper in the most recent issue of JAMA Health Forum, by a team that includes both medical professionals and market designers.

Weighted Lottery to Equitably Allocate Scarce Supply of COVID-19 Monoclonal Antibody , by Erin K. McCreary, PharmD1; Utibe R. Essien, MD, MPH2,3; Chung-Chou H. Chang, PhD4,5; Rachel A. Butler, MHA, MPH6; Parag Pathak, PhD7; Tayfun Sönmez, PhD8; M. Utku Ünver, PhD8; Ashley Steiner, BS9; Maddie Chrisman, PT, DPT10; Derek C. Angus, MD, MPH11; Douglas B. White, MD, MAS11, JAMA Health Forum. 2023;4(9):e232774. Sept. 1, doi:10.1001/jamahealthforum.2023.2774 

"Objective  To describe the development and use of a weighted lottery to allocate a scarce supply of tixagevimab with cilgavimab as preexposure prophylaxis to COVID-19 for immunocompromised individuals and examine whether this promoted equitable allocation to disadvantaged populations.

"Design, Setting, and Participants  This quality improvement study analyzed a weighted lottery process from December 8, 2021, to February 23, 2022, that assigned twice the odds of drug allocation of 450 tixagevimab with cilgavimab doses to individuals residing in highly disadvantaged neighborhoods according to the US Area Deprivation Index (ADI) in a 35-hospital system in Pennsylvania, New York, and Maryland. In all, 10 834 individuals were eligible for the lottery. Weighted lottery results were compared with 10 000 simulated unweighted lotteries in the same cohort performed after drug allocation occurred.

"Main Outcomes:  Proportion of individuals from disadvantaged neighborhoods and Black individuals who were allocated and received tixagevimab with cilgavimab.

"Results:  Of the 10 834 eligible individuals, 1800 (16.6%) were from disadvantaged neighborhoods and 767 (7.1%) were Black. Mean (SD) age was 62.9 (18.8) years, and 5471 (50.5%) were women. A higher proportion of individuals from disadvantaged neighborhoods was allocated the drug in the ADI-weighted lottery compared with the unweighted lottery (29.1% vs 16.6%; P < .001). The proportion of Black individuals allocated the drug was greater in the weighted lottery (9.1% vs 7.1%; P < .001). Among the 450 individuals allocated tixagevimab with cilgavimab in the ADI-weighted lottery, similar proportions of individuals from disadvantaged neighborhoods accepted the allocation and received the drug compared with those from other neighborhoods (27.5% vs 27.9%; P = .93). However, Black individuals allocated the drug were less likely to receive it compared with White individuals (3 of 41 [7.3%] vs 118 of 402 [29.4%]; P = .003).

...

"Conclusions and Relevance:  The findings of this quality improvement study suggest an ADI-weighted lottery process to allocate scarce resources is feasible in a large health system and resulted in more drug allocation to and receipt of drug by individuals who reside in disadvantaged neighborhoods. Although the ADI-weighted lottery also resulted in more drug allocation to Black individuals compared with an unweighted process, they were less likely to accept allocation and receive it compared with White individuals. Further strategies are needed to ensure that Black individuals receive scarce medications allocated."

...

"The lottery was repeated over several weeks, but we chose to examine only the first assignment. The interpretation of later rounds is problematic because eventually all individuals were offered tixagevimab with cilgavimab. By focusing on the first draw, we can specifically evaluate whether the intent of the lottery was met."

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Closely related reports:

White, D.B., McCreary, E.K., Chang, C.C.H., Schmidhofer, M., Bariola, J.R., Jonassaint, N.N., Persad, G., Truog, R.D., Pathak, P., Sonmez, T. and Unver, M.U., 2022. A multicenter weighted lottery to equitably allocate scarce COVID-19 therapeutics. American Journal of Respiratory and Critical Care Medicine, 206(4), pp.503-506.

Rubin, E., Dryden-Peterson, S.L., Hammond, S.P., Lennes, I., Letourneau, A.R., Pathak, P., Sonmez, T. and Ünver, M.U., 2021. A novel approach to equitable distribution of scarce therapeutics: institutional experience implementing a reserve system for allocation of COVID-19 monoclonal antibodies. Chest, 160(6), pp.2324-2331.*

White, D.B. and Angus, D.C., 2020. A proposed lottery system to allocate scarce COVID-19 medications: promoting fairness and generating knowledge. Jama, 324(4), pp.329-330.

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And here's an editorial in the same issue of JAMA Health Forum as the most recent article, pointing out that less-disadvantaged patients among those living in census blocks identified as disadvantaged (in particular  commercially insured and White patients) were much more likely to receive the treatment:

Moving Beyond Intent and Realizing Health Equity, by Atheendar S. Venkataramani, MD, PhD, Invited Commentary, September 1, 2023, JAMA Health Forum. 2023;4(9):e232525. doi:10.1001/jamahealthforum.2023.2525

"In a study published in this issue of JAMA Health Forum, McCreary and colleagues3 report on a landmark effort at the University of Pittsburgh Medical Center (UPMC) to distribute equitably a scarce monoclonal antibody resource, tixagevimab with cilgavimab, for COVID-19 preexposure prophylaxis in immunocompromised individuals. In December 2021, UPMC received an allotment of 450 doses of tixagevimab with cilgavimab from the Pennsylvania Department of Health to cover a large health system with 35 hospitals and 800 outpatient facilities through February 2022. In an ex ante effort to mitigate health disparities and respond to guidance from the Commonwealth of Pennsylvania to allocate scarce resources in a manner that accounts for multiple ethical objectives, UPMC convened an advisory group of clinicians, community stakeholders, and experts in community outreach.

...

"The lottery was constructed using the Area Deprivation Index (ADI) to ensure that patients in highly disadvantaged neighborhoods had an equal opportunity to access tixagevimab with cilgavimab. Patients living in neighborhoods with ADIs above a specific cutoff that has been shown to best target less affluent, rural, and Black patients received 2 entries in the lottery, compared with 1 entry for patients in more advantaged neighborhoods. In their study, McCreary and colleagues3 found that this process resulted in equitable access: similar proportions of individuals in more advantaged and more disadvantaged neighborhoods (about 28% in each group) received tixagevimab with cilgavimab during the study period, although Black patients who were allocated the drug in the lottery were significantly less likely to receive it compared with White patients (7.3% vs 29.4%).

...

"Having identified its patient population, UPMC required only patient addresses as well as publicly available data on ADIs to implement the lottery intervention. The ADIs are defined at the census block group level, which include about 1000 residents on average. Thus, UPMC was able to achieve equitable opportunity to access tixagevimab with cilgavimab across small localities with very different socioeconomic profiles.

...

On the other hand, higher-resolution data that specifically measure the types of intersecting, reinforcing, and cumulative disadvantages faced by historically marginalized groups5 may be needed to achieve equitable outcomes across other dimensions, such as race and ethnicity. Within census blocks, patients assigned the same ADI levels but who may have faced relatively fewer structural barriers compared with Black patients or patients receiving Medicaid—namely, commercially insured and White patients—were more likely to access tixagevimab with cilgavimab conditional on being allocated to receive it in the lottery

...

"The lower rates of drug receipt among Black patients also underscores the importance of complementary investments and operational decisions to address additional structural barriers to accessing medical technology.

...

"The study by McCreary and colleagues3 represents the type of courageous and rigorous work that is needed to chart a path forward in determining how best to bridge the access gap for leading-edge medical technology. Future work would benefit from the same type of clarity demonstrated in this study by including clear definitions for how equity should be operationalized, attempting to address fragmentation between clinical services and services that address social drivers of health, aligning incentives, and addressing historical barriers that have made it difficult to achieve health equity."

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*Earlier:

Saturday, August 14, 2021


Saturday, August 26, 2023

Challenge trials for a Hepatitis C vaccine

 The Journal Clinical Infectious Diseases has a special supplement on challenge trials (human infection trials) of a Hep C vaccine (now that Hep C is a curable disease):

Volume 77, Issue Supplement_3, 15 August 2023

SUPPLEMENT ARTICLES

T Jake Liang and others
Clinical Infectious Diseases, Volume 77, Issue Supplement_3, 15 August 2023, Page S215, https://doi.org/10.1093/cid/ciad343
Annette Rid and others
Clinical Infectious Diseases, Volume 77, Issue Supplement_3, 15 August 2023, Pages S216–S223, https://doi.org/10.1093/cid/ciad382
Jake D Eberts and others
Clinical Infectious Diseases, Volume 77, Issue Supplement_3, 15 August 2023, Pages S224–S230, https://doi.org/10.1093/cid/ciad350

The perspectives of former challenge study participants and a survey of other potential volunteers can inform the design of hepatitis C virus controlled human infection models, including on topics such as transparency, volunteer safety and risk, and compensation.

Alyssa Bilinski and others
Clinical Infectious Diseases, Volume 77, Issue Supplement_3, 15 August 2023, Pages S231–S237, https://doi.org/10.1093/cid/ciad379