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

Eliminating Hepatitis C, now that there's a cure (even though it's expensive)

Saturday, August 26, 2023

Challenge trials for a Hepatitis C vaccine

Sunday, November 1, 2020

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

New technologies and new controversies: using CRISPR to edit human genes

 New technologies are often accompanied by new repugnancies, i.e. by controversies about their moral appropriateness. The future of using CRISPR to edit human genes is still before us, and its history (even to date) has yet to be written. But I'm struck by how it both interacts with and recapitulates older controversies and repugnancies, including those involving HIV, and adoption and assisted reproduction.

The New Yorker has the story:

The Transformative, Alarming Power of Gene Editing. A rogue scientist showed that crispr gives humans the ability to transform ourselves. But should we?  By Dana Goodyear  September 2, 2023

"The Chinese researcher He Jiankui was jailed for creating customized babies. Some observers argue that the real problem wasn’t him—it was the lure of the technology.

...

"To start, he would focus on what he believed was an achievable task: eradicating a disease governed by a single gene. He selected aids, an illness regarded in China as both pernicious and shameful but one for which there might be an elegant fix. H.I.V. enters human cells by way of a receptor created by a gene called CCR5. JK planned to use the gene-editing tool crispr to disrupt CCR5 in human embryos, which would, in theory, render the babies impervious to infection.

"The experiment required volunteers, and, through a chat group associated with an H.I.V./aids charity, he began recruiting couples: H.I.V.-positive men married to uninfected women. Chinese law denies in-vitro fertilization and adoption to H.I.V.-positive people, and natural conception carries a risk of transmission. For couples with an infected partner, JK’s program was a chance at parenthood. It promised confidentiality, which was critical for a marginalized community; an H.I.V. diagnosis in China can cost a person his job. The treatments would take place discreetly, at facilities where only key employees were aware of the experiment.

...

"as scientists from around the world prepared for a gene-editing conference in Hong Kong, JK released a series of YouTube videos, announcing the birth of a set of twins, edited as embryos with crispr. A slim, nervous-seeming man in a pale-blue shirt, he looked earnestly into the camera and said, “Two beautiful little Chinese girls named Lulu and Nana came crying into the world, as healthy as any other babies.” He went on to explain how, when each was only a single cell, he had used crispr to delete CCR5. “I understand my work will be controversial,” he said. “But I believe families need this technology, and I’m willing to take the criticism for them.”

"China’s state-run media celebrated the news, but the scientific community reacted with dismay. A group of Chinese researchers condemned the study as madness. David Baltimore, a Nobel Prize-winning biologist who chaired the Hong Kong event, called it “irresponsible,” saying, “I think there has been a failure of self-regulation by the scientific community.

...

"There were three edited babies, he acknowledged: along with Lulu and Nana, another was on the way.

...

"The Chinese government swiftly withdrew its enthusiasm for JK’s research, and, soon after he returned to the mainland, his lab was locked and he was placed under house arrest. In 2019, he was sentenced to three years in prison for “illegal medical practices,” and fined nearly half a million dollars. Two of his collaborators were given lesser sentences and fined. Among scientists, there was a pervasive sense of embarrassment. JK had misused a powerful technology and gambled with the health of children—experimental subjects he himself had created—without, in the scientists’ view, a compelling medical reason to compensate for the risk. Urnov told me, “He has taken a jar of tar, poured it over the field of crispr, and left an indelible stain. We will never wash that stain off. I am prepared to say that he’s not a fellow-scientist. He’s persona non grata.”

"JK was released from prison in the spring of 2022, and quickly resumed his efforts at gene editing. 

...

"He said that his new lab would be a nonprofit providing affordable gene therapy for rare conditions, and that he would focus first on Duchenne muscular dystrophy, a fatal disease that causes irreversible muscle damage, primarily in boys. This time, his patients would be not embryos but young children desperate for a cure. I asked if it was an attempt to redeem himself in the scientific community. “I don’t know if I’d use the word ‘redeem,’ ” he said. “I want to do it to help people today.”

...

"As for the debacle that his experiment had caused, JK would admit to no greater error than bad timing. “I do acknowledge that I have done it too quickly,” he said. In one of his YouTube videos, he predicted that in twenty or thirty years gene-edited babies will no longer be controversial, or even remarkable. He likened himself to the pioneering founder of the field of I.V.F., Robert Edwards, whose career had followed a heroic arc. In 1978, when the first I.V.F. baby was born, Edwards was a figure of scandal and opprobrium. In 2010, he was awarded the Nobel Prize."

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.

###

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."

##########

*Earlier:

Saturday, August 14, 2021

A lottery for antibody treatment, with slots reserved for vulnerable patients

Innovations in medicine: psychedelic drugs to treat depression

 Here's an editorial in JAMA that accompanies a report on treating some depressive patients using psilocybin therapy.

Psychedelic Therapy—A New Paradigm of Care for Mental Health, by Rachel Yehuda, PhD Amy Lehrner, PhD JAMA. Published online August 31, 2023. doi:10.1001/jama.2023.12900

"An increasing number of clinicians and researchers have become interested in the potential of psychedelic drugs for the treatment of mental health disorders, including depression, anxiety, posttraumatic stress disorder, eating disorders, and addictions.1,2

"Currently, most psychedelic compounds are illegal under federal law. They were placed on the most restrictive class of drugs, Schedule I, in the 1970s as part of the “war on drugs,” meaning that they were considered to have high potential for abuse with no accepted medical use.2 However, the ever-growing global mental health crisis, coupled with the shortage of effective therapeutic strategies, has given rise to a reconsideration of the therapeutic potential of these compounds in recent years.

...

"The study by Raison et al provides an excellent example of the promise of this new approach using psilocybin therapy for patients with major depressive disorder.3 Although the trial was relatively small, it demonstrated that a single dose of psilocybin in the context of a 6-week period that included active psychotherapy resulted in a rapid, robust, and sustained reduction in depressive symptoms.

"Psilocybin is a naturally occurring compound belonging to a class of compounds known as tryptamines, similar to lysergic acid diethylamide (LSD), dimethyltryptamine (DMT), and mescaline. Understanding its therapeutic efficacy requires an appreciation of the context in which it is used, and not just its pharmacological profile or biological mechanism of action. The psychotherapy that occurs with the psychedelic medication is a critical component of this approach.4

...

"The social, economic, and public health impacts of untreated mental disorders demand solutions. If psychedelic therapies do prove to have enduring effects after just a single or a few administrations in the context of a few sessions for preparation and integration, they have the potential to offer not just a new approach to mental health care, but an entirely new paradigm of care."

Unclaimed bodies and medical school anatomy classes.

 There's a long history of unclaimed bodies being used in medical school anatomy classes. (I think the historical availability of such cadavers is one of the reasons that the Harvard Medical School is in Boston rather than Cambridge.*)  Here's an update on the practice, in Texas.

Unclaimed Bodies and Medical Education in Texas, by Eli Shupe, PhD1; Serena Karim2; Daniel Sledge, PhD, JAMA.  online August 24, 2023

"The use of unclaimed bodies (bodies not claimed by next of kin for burial or cremation) in gross anatomy education in the US has declined substantially since the middle of the 20th century owing to increases in voluntary donations and escalating ethical concerns.1-3 Nonetheless, in most US jurisdictions, counties can donate unclaimed bodies to science without consent from the deceased or their next of kin, with some medical schools still accepting such donations. The current scope and magnitude of the use of unclaimed bodies in the US is underresearched, although one 2019 study found that anatomy course leaders at 12.4% of surveyed US medical schools indicated possible use of unclaimed bodies at their institutions.4 The objective of this study was to examine the trends in use of unclaimed bodies in medical education in Texas.

...

"We found that during 2017-2021, 6 of the 14 medical schools in our sample (42.9%) either engaged in the direct procurement and use of unclaimed bodies (2 schools, 14.3%) or received transferred cadavers from schools that did (4 schools, 28.6%). The remaining 8 schools (57.1%) had no possible use of unclaimed bodies."

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*Here's a related story from the Harvard Crimson:

Harvard's Habeas Corpus: Grave Robbing at Harvard Medical School, BY NURIYA SAIFULINA, September 28, 2017

"Harvard’s corpse legacy began in late 18th century, when the newly opened Medical School began hiring grave diggers—not to bury bodies, but to exhume them. According to a 2015 history of the so-called “resurrection men” in Synthesis, an undergraduate history of science journal, the diggers snuck into Boston’s burial grounds in search of new graves, stealthily dug up some of the most “fresh” residents, and refilled the graves to avoid arousing suspicion.

...

"Around 1770, Joseph Warren founded an illicit secret society called the “Spunker Club,” also known as the “Anatomical Club.” His older brother, John Warren—the founder of Harvard Medical School—was also a member. Some of the club’s most notable members included a William Eustis, the future governor of Massachusetts, and Samuel Adams’ son.

...

"As “resurrection men” and body-snatching enthusiasts continued to ransack Boston graveyards, civil indignation incited the Act to Protect the Sepulchers of the Dead in 1815, making disturbance of buried bodies illegal and prompting a citywide patrol of graveyards and burial grounds.

"This legislature forced Harvard Medical School to “import” the cadavers from New York instead, where body snatchers were “emptying at least six hundred or seven hundred graves annually,” according to an article in the Boston Gazette.

"After the Massachusetts Medical Society published a plea in 1829 claiming that medical students had no other choice but to pursue their studies “in defiance of the law of the land,” the school’s need for illegally-obtained cadavers waned. Massachusetts passed the Anatomy Act of 1831, which allowed for dissection of the unclaimed bodies of the indigent, insane and imprisoned."

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

Controlled Human Infection Model for HCV Vaccine Development

SUPPLEMENT ARTICLES

Controlled Human Infection Model for Hepatitis C Virus Vaccine Development: Is It Time to Be Real? 

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

• Hepatitis C virus (HCV) elimination has been a goal of the public health and scientific communities since its identification in 1989. Despite the advance and availability of highly effective antiviral regimens to treat HCV infection, it is unlikely that global HCV elimination can be achieved without an effective preventive vaccine. Because of the lack of appropriate animal models for preclinical testing and the perception that highly effective treatments would suffice in addressing the global burden of HCV, HCV vaccine development has not been a high priority. To accelerate vaccine development, the concept of a controlled human infection model (CHIM) for HCV has been proposed, in which healthy human volunteers would be deliberately infected with HCV for the purpose of testing the efficacy of candidate vaccines. This concept of challenge studies is not new and has been applied to more than 25 infectious agents, including the cholera vaccine, for which all efficacy data that served as the basis for regulatory approval were obtained from CHIM studies. Without a CHIM strategy, HCV vaccine development may not be feasible. In a recent phase 2 randomized controlled trial, over 900 people who inject drugs were screened to enroll 548 individuals to receive a T-cell–based HCV vaccine candidate or placebo. After a monumental effort that took over 6 years to complete, the trial documented 75 incident HCV infections overall, with only 45 included in the final analysis, and showed no protection against initial infection or progression to chronicity with the vaccine. While this study demonstrated that vaccine testing in the at-risk population can be done, future testing of additional HCV vaccine candidates using a similar pathway may be impractical in light of the duration and cost. With the ability to cure those who do not clear the virus, HCV CHIM is now a conceivable approach that could be a critically important, if not necessary, intermediate stage of vaccine development. HCV CHIM could de-risk vaccine candidates, accelerate development, reduce cost, and allow the selection of more promising candidates for further testing in larger clinical trials. CHIM may conceivably be used for larger phase 2/3 efficacy trials as a basis for clinical approval. In developing such a model, many challenges and questions must be addressed. In this Supplement issue, we, the editors of this Supplement commissioned various articles written by respective subject matter experts who provide their perspectives and opinions on these challenges and questions, ranging from the source of viral inoculum and the safety of transient HCV infection to the perspective of potential volunteers and the ethics of CHIM. While we strive to be data-driven and evidence-based, some of the opinions represent the views of the authors of each article and may be controversial. Ultimately, we hope these perspectives will enable fulsome discussion about the feasibility of HCV CHIM and lead to the development of well-designed clinical protocols.

  Supplement sponsorship. This article appears as part of the supplement “Controlled Human Infection Model for HCV Vaccine Development,” sponsored by Toronto General Research Institute, United States National Institutes of Health, Johns Hopkins University, the Canadian Institutes of Health Research (CIHR), and the Canadian Network on Hepatitis C (CanHepC). CanHepC is funded by a joint initiative of CIHR (HPC-178912) and the Public Health Agency of Canada.

• View article

Ethics of Controlled Human Infection Studies With Hepatitis C Virus 

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

• Global elimination of hepatitis C virus (HCV) will be difficult to attain without an effective HCV vaccine. Controlled human infection (CHI) studies with HCV were not considered until recently, when highly effective treatment became available. However, now that successful treatment of a deliberate HCV infection is feasible, it is imperative to evaluate the ethics of establishing a program of HCV CHI research. Here, we evaluate the ethics of studies to develop an HCV CHI model in light of 10 ethical considerations: sufficient social value, reasonable risk–benefit profile, suitable site selection, fair participant selection, robust informed consent, proportionate compensation or payment, context-specific stakeholder engagement, fair and open collaboration, independent review and oversight, and integrated ethics research. We conclude that it can be ethically acceptable to develop an HCV CHI model. Indeed, when done appropriately, developing a model should be a priority on the path toward global elimination of HCV.

• View article 
• Supplementary data

Volunteering for Infection: Participant Perspectives on a Hepatitis C Virus Controlled Human Infection Model 

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.

• Ethical human subjects research requires participants to be treated safely and respectfully, yet much bioethical debate takes place without participants. We aim to address this gap in the context of controlled human infection model (CHIM) research. Based upon our own experience as study participants, and bolstered by a survey of 117 potential hepatitis C virus CHIM participants, we present ideas to inform efficient, ethical, and scientifically useful study design. We advocate for full protocol transparency, higher compensation, commitment to the rapid dissemination of study results, and proactive efforts to detail risk-minimization efforts as early as possible in the recruitment process, among other measures. We encourage researchers to proactively partner with volunteer advocacy organizations that promote collective representation of volunteers to maximize their agency, and guard against ethical issues arising from healthy human subjects research.

• View article 
• Supplementary data

First Do No Harm? Modeling Risks and Benefits of Challenge Trials for Hepatitis C Vaccine DevelopmentGet access

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

• Background

  In 2019, about 58 million individuals were chronically infected with hepatitis C virus. Some experts have proposed challenge trials for hepatitis C virus vaccine development.

  Methods

  We modeled incremental infections averted through a challenge approach, under varying assumptions regarding trial duration, number of candidates, and vaccine uptake. We computed the benefit-risk ratio of incremental benefits to risks for challenge versus traditional approaches. We also benchmarked against monetary costs of achieving incremental benefits through treatment.

  Results

  Our base case assumes 3 vaccine candidates, each with an 11% chance of success, corresponding to a 30% probability of successfully developing a vaccine. Given this probability, and assuming a 5-year difference in duration between challenge and traditional trials, a challenge approach would avert an expected 185 000 incremental infections with 20% steady-state uptake compared to a traditional approach and 832 000 with 90% uptake (quality-adjusted life-year benefit-risk ratio, 72 000 & 323 000). It would cost at least $92 million and $416 million, respectively, to obtain equivalent benefits through treatment. BRRs vary considerably across scenarios, depending on input assumptions.

  Conclusions

  Benefits of a challenge approach increase with more vaccine candidates, faster challenge trials, and greater uptake.

• View article 
• Supplementary data
• **********
  Earlier:

  Monday, May 15, 2023

  Eliminating Hepatitis C, now that there's a cure (even though it's expensive

  and here are my posts on challenge trials (and Covid vaccines).