Human challenge trials wiki

Human challenge trials wiki DEFAULT

What is ‘human challenge’ that UK cleared to speed up Covid vaccine trial?

After mulling over the idea for a few days, the UK government on October 20 has given a go-ahead to start ‘human challenge’ trial so that an effective vaccine can be produced at the earliest. The concept of human challenge trial is not new, but it remains controversial as participants in such a trial are injected with the virus.

Here is all you need to know about human challenge trial and UK’s plan:

1. Amid the ongoing pandemic, the race for a fast and effective vaccine has now become intense. Russia has become the first country to have announced its vaccine against Covid, which has been tested amid a small number of people before its registration, which is why questions over the efficacy of the vaccines remain. The United Kingdom is also leaving no stones unturned to become a frontrunner in this race.

2. UK’s human challenge trial plan has an investment of million pound from the National Health Services.

3. Under this programme, the participants will first be administered a vaccine candidate that has proven safe so far. Then they will be exposed to the Covid virus in a safe and controlled environment. The participants will be monitored by researchers who will thus explore how the vaccine is working, how much virus can infect a group of healthy people etc — aspects that will bolster the vaccine research.

4. Since human challenge trial is risky, it will only involve healthy people belonging to the age group of 18 to

5. About 90 participants, who will be compensated by the government, will take part in UK’s human challenge trial.

6. Human challenge trial will help researchers find out which vaccine is the most promising one.

7. The researchers are also hoping to find answers to whether vaccines can prevent only illness or whether vaccine can stop transmission.

8. The participants will be monitored for up to a year to find out if there is any long-term illness.

9. UK’s plan is subject to the approval of regulators and the ethics committee. Once approved, the study will start in January and the results are expected by May

Human challenge studies were conducted for cholera, typhoid, malaria, influenza, tuberculosis, dengue etc.

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“Human challenge trials,” where healthy volunteers would be exposed to Covid, explained

As a journalist who covers philanthropy, one of the most frequent questions I get about the coronavirus crisis is how ordinary people can help.

A couple things leap to mind. GiveDirectly is giving money to poor Americans struggling with unemployment and other hardships; you can also donate money to other public health charities helping poor countries handle a sudden surge in demand for doctors and hospitals.

Now, a bioethicist and two epidemiologists are proposing a bolder option: You can volunteer to get infected yourself.

In a recent article published in the Journal of Infectious Diseases, bioethicist Nir Eyal and epidemiologists Marc Lipsitch and Peter G. Smith called for “human challenge studies” to test the effectiveness of coronavirus vaccines as they’re developed. These studies would involve testing the vaccines on a group of volunteers who have been knowingly exposed to the novel coronavirus that causes Covid The hope is that it will allow researchers to ascertain more quickly and conclusively the effectiveness of the proposed vaccine.

Human challenge studies are commonly conducted with less lethal diseases like malaria or schistosomiasis. My colleague Kelsey Piper interviewed John Beshir, a volunteer in a malaria vaccine trial, last year; Beshir is an active donor to anti-malaria charities and saw his volunteering as an extension of his monetary support for the cause.

But malaria, if properly treated, has a low death rate for young and healthy people (that it still kills hundreds of thousands of people every year is partially a reflection of the poor availability of treatment in heavily affected African countries). Covid is different. About percent of people who are infected die from the disease. And while a recent study showed that death rates are much lower for younger people ( percent for people in their 20s) the data on which it’s based is from the early stages of the Chinese outbreak in February. There’s still a lot we don’t know about the disease and its lethality.

Activist Josh Morrison, whom I know from his day job advocating for living kidney donors (like me), has started a website soliciting volunteers willing to take on that deadly risk for the sake of speeding up vaccine development. As of this writing, about people have expressed provisional interest in volunteering (including me, though I may not be eligible with only one kidney).

Signing up doesn’t commit you to anything, and the website isn’t recruiting for any current trial. No vaccine is in the stage of development where a human challenge trial would make sense. The Milken Institute counts 51 different vaccines currently in development, with only a smallhandful in Phase I trials, which involve making sure the vaccine isn’t dangerous to humans. After that comes Phase II trials, which use a larger sample and do preliminary tests for efficacy and to find an optimal dose with the best balance of side effects and effectiveness. Some studies combine Phases I and II, which could speed the process up.

Eyal, Lipsitch, and Smith propose using a human challenge trial to replace Phase III, where larger-sample effectiveness tests take place (and which are, at the very least, months in the future). Instead of a typical Phase III, a human challenge trial could involve fewer people and run for a much shorter period of time, since researchers would not have to wait for volunteers to be exposed to the virus. A real human challenge trial would involve intensive health screening for volunteers, as well as voluminous risk disclosures to ensure that volunteers know exactly what they (we) are getting into.

But the push to sign up volunteers is forcing a broader conversation about whether this kind of trial is necessary or ethical, given the death toll that coronavirus threatens to leave in its wake. The ethical question here is knotty, and depends on both empirical questions — Would a human challenge trial actually speed up vaccine development? How many lives would be saved by speeding up development by, say, one month? — and values questions.

The big one: Is it acceptable to ask volunteers to risk their lives to speed up vaccine development? And if so, should they be eligible for nominal compensation (like lost wages) or something more?

“We’re all looking for a Hail Mary, and it’s easy to see challenge studies as exciting and having a lot of promise,” says Seema Shah, professor of medical ethics at Northwestern University Medical School and a practicing medical ethicist at Lurie Children’s Hospital of Chicago who has written about the ethics of human challenge trials. “But a lot of things need to fall into place to achieve that promise.”

How human challenge trials work

Testing something like a coronavirus vaccine normally happens by gathering a group of healthy people, giving half of them the experimental vaccine and the other half a placebo, and waiting for them to get infected with the relevant disease in the course of their regular lives. Then you compare the groups.

The problem with the coronavirus is that if you’re a healthy person who’s practicing social distancing, you probably aren’t going to get infected. That makes it hard to do a real comparison between the vaccinated and unvaccinated groups. Maybe they both end up the same because no one in either group was exposed to the pathogen. If that’s the case, the trial hasn’t told us anything useful.

A human challenge trial replaces that process with one in which all of the trial volunteers are exposed to the virus that causes Covid after being dosed with a vaccine or placebo. That way, you get a much clearer sense of how the vaccine performs when actually confronted with the disease it’s intended to guard against.

“To allow for a high portion to get exposed, the standard trial would have to take at least several months,” Eyal, the bioethicist who co-authored the Journal of Infectious Diseases article calling for human challenge trials, told me. “By contrast, in a coronavirus challenge the success or failure of the vaccine to protect against the disease becomes apparent much faster.”

What’s more, a human challenge trial could be conducted with fewer people than a standard Phase III trial. A Covid vaccine being developed at Oxford, for instance, aims to have 5, volunteers for Phase III. A human challenge trial, Eyal argues, could happen with only about people. The total number of participants needed would likely be higher than that, since (among other reasons) multiple vaccine candidates need to be tested, but the total would be much lower compared with a conventional study.

The risks of conducting a human challenge trial, and how to mitigate them

The downside to doing this is obvious: Covid is a dangerous disease, and it’s possible that volunteers in the placebo group especially — but also in the treatment group, given that all vaccines have a failure rate — will become badly ill, need weeks of hospitalization, and/or die.

Eyal has a number of answers to this objection. He anticipates that the volunteer pool would be limited to healthy people between the ages of 20 and “Preexisting conditions that increase the risk of bad outcomes upon coronavirus infection” — such as asthma and other chronic lung diseases, HIV and other immunocompromising conditions, obesity, diabetes, liver disease, and chronic kidney disease — “should exclude a volunteer,” Eyal says. That should help reduce the odds of an infection leading to death.

Currently, per a study published in the Lancet on March 30, only percent of people in their 20s who were infected with the virus causing Covid have died — and that includes people with underlying conditions. That’s almost identical to the risk of death from living kidney donation, which medical facilities treat as acceptable.

What’s more, volunteers would be “isolated from their families in special facilities, potentially facilities for flu challenge trials, which exist in a few developed countries, converted to this usage,” Eyal says. “They should remain in isolation until they stop being infectious. Upon detection of infection, they should get excellent medical care for coronavirus disease — much more than we can say about the general health system in the upcoming time of crisis.”

Eyal and his co-authors also want to recruit “people who reside in high-transmission environments” like New York City, so that “being in the study would hardly increase, or in fact decrease, their net risk.”

Reasons for apprehension

Shah, the Northwestern bioethicist, believes that the risks of a human challenge trial might be acceptable if the benefits are sufficiently large. “If you were really careful about who you enrolled — people who are 18 to 25, for instance, and carefully evaluated so they have no other condition — you could get the risk down to a low level,” she explains. You’d also want to make sure that the risks to third parties, like the families of volunteers and the medical personnel treating them, are similarly reduced.

But you have to do more than weigh the risks and benefits, Shah cautions. “When judging the ethics of doing a study, justice considerations also matter, such as whether the risks are fairly distributed,” she says. “There are also other criteria: community engagement, fair selection of participants, robust informed consent, and payment that compensates for time and inconveniences.”

Shah cautions that estimating the benefits of a human challenge trial is difficult, and that the magnitude of the benefits depends heavily on the ability to coordinate between vaccine trials and researchers. Researchers would need assurances that regulators like the Food and Drug Administration would actually accept a human challenge trial as evidence of effectiveness; the FDA might have its own ethical concerns or be wary of going around standard procedure. If the FDA doesn’t approve a vaccine that’s been tested in a human challenge trial, the tests might not speed up vaccine adoption at all.

Similarly, Shah notes that you would need different vaccine teams to use comparable doses and share data, so they can judge which vaccine shows the most promise. Given how international this effort is, the coordination would need to happen through an international body like the World Health Organization.

Without those ducks in a row, Shah warns, the benefits to a challenge trial could be severely attenuated.

Given how far we have to go until a human challenge trial would be applicable, now is a good time to get that kind of coordination in place: for the FDA to issue guidance on whether it would consider human challenge trial results acceptable as evidence; for the various biotech companies, research institutes, and governments working on vaccines to coordinate evidence and data sharing; and for clinicians to offer input so that the vaccines being tested on human subjects are ones likely to be of use in the field.

Once those elements are in place, the case for human challenge trials will be much more compelling.

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Human challenge study

Intentional exposure of test subjects to a pathogen to test a vaccine or drug

A human challenge study, also called a controlled human infection trial, is a type of clinical trial for a vaccine or other pharmaceutical involving the intentional exposure of the test subject to the condition tested.[1][2][3] Human challenge studies may be ethically controversial because they involve exposing test subjects to dangers beyond those posed by potential side effects of the substance being tested.[2][3]

During the 21st century, the number of human challenge studies has been increasing.[4][5] A challenge study to test promising vaccines for prevention of COVID disease was under consideration during by several vaccine developers, including the World Health Organization (WHO),[6][7] and was approved in the UK in [8]

Over the 20th and 21st centuries, vaccines for some 15 major pathogens have been fast-tracked in human challenge studies – involving about 30, participants who had no serious adverse effects – while contributing toward vaccine development to prevent cholera, typhoid, seasonal flu, and other infections.[9] According to medical ethicists, methods of conducting clinical trials by human challenge testing have improved over the 21st century to satisfy ethical, safety, and regulatory requirements, becoming scientifically acceptable and ethically valid as long as participants are well-informed and volunteer freely, and the trials adhere to established rigor for conducting clinical research.[2][3][9]

Design[edit]

The intent of a challenge study is to fast-track the timeline for providing evidence of safety and efficacy of a therapeutic drug or vaccine, especially by compressing (to a few months) the usually lengthy duration of Phase&#;II–III trials (typically, many years).[2][3][10] Following preliminary proof of safety and efficacy of a candidate drug or vaccine in laboratory animals and healthy humans, controlled "challenge" studies may be implemented to bypass typical Phase&#;III research, providing an accelerated path to regulatory approval of the test compound for widespread prevention against an infectious disease, such as COVID‑[2][7]

The design of a challenge study involves first, simultaneously testing a vaccine candidate for immunogenicity and safety in laboratory animals and healthy adult volunteers ( or fewer)&#;&#; which is usually a sequential process using animals first&#;&#; and second, rapidly advancing its effective dose into a large-scale Phase&#;II–III trial in low-risk, healthy volunteers (such as young adults), who would then be deliberately infected with the disease being tested against for comparison with a placebo control group.[2][3][7] In a challenge study for a vaccine to prevent an infectious disease, participants would be closely monitored for signs of toxicity and adequate immune response, such as by producing substantial levels of antibodies against the virus causing the disease.[2][3][6]

Ethics[edit]

Awareness of the history of challenge trials is indispensable, including trials that were problematic or even connected to abuse.[11] Special ethical issues can arise when a wealthy country finances and organizes these clinical trials in a less wealthy country.[12]

Two commonly discussed general thresholds for risk to research participant are minimizing all risk after the infection and avoiding serious injury.[13] Researchers typically customize other thresholds for each clinical trial.[13]

Vaccines for viral infections[edit]

Challenge studies have been used to expedite evaluation of vaccines for several pandemic viral diseases,[3] such as cholera,[14] typhoid fever,[15] malaria,[16] influenza,[1]streptococcal pharyngitis,[17]tuberculosis,[18]shigella,[19]pertussis,[20] and dengue fever.[21]

Other than expediting clinical evaluation of vaccine properties, advantages of using challenge studies for vaccine candidates include minimizing bias which is inherently part of traditional cohort studies, as both the exposure (timing of infection, virus challenge dose) and outcome (assessment of blood biomarkers) are standardized.[16] Disadvantages include high cost of conducting the trial at multiple locations and the complex management of infrastructure for a challenge trial, especially for obtaining national regulatory approval, organizing participants and trial personnel, and implementing laboratories with Good Clinical Laboratory Practice qualifications.[16] Before beginning a challenge study, a vaccine sponsor must have demonstrated Good Manufacturing Practice standards for approval to use the candidate vaccine in humans, including expensive toxicology and immunogenicity testing.[16][22] The vaccine sponsor may have required proof of safety and efficacy of adjuvants for delivering the vaccine, demonstrated what the effective vaccination schedule may be, and coordinated with international regulatory agencies and bioethicists for approval and eventual distribution, all requiring coordinated financing and planning.[16]

COVID[edit]

See also: COVID vaccine clinical research §&#;Trial and authorization status

Human challenge studies are under consideration to hasten the development of a COVID vaccine,[3][7][23] including one proposal made by bioethicist Nir Eyal,[2] and another by rubella vaccine inventor Stanley Plotkin with bioethicist Arthur Caplan.[22] These authors propose that the multi-year duration and multinational location of a typical Phase III efficacy clinical trial will continue as usual, while people infected with COVID will continue to suffer or die.[22] As an alternative based on emerging results from COVID vaccine challenge studies, regulatory agencies could allow early emergency use of the vaccine, while the challenge study continues collecting data for eventual licensure.[22]

In May , a guidance document was issued by the WHO on criteria for conducting challenge clinical trials and providing clinical care for the participants.[6] Following the challenge infection with or without the candidate vaccine, volunteers would be monitored closely in hospitals or clinics managed by physicians treating people with COVID disease and with life-saving resources, if needed.[2][3][6] Volunteering for a vaccine challenge study during the COVID‑19 pandemic is likened to the emergency service of healthcare personnel for COVID‑infected people, firefighters, or organ donors.[2][3]

References[edit]

  1. ^ abLambkin-Williams, Rob; Noulin, Nicolas; Mann, Alex; Catchpole, Andrew; Gilbert, Anthony S. (22 June ). "The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics". Respiratory Research. 19 (1): doi/s ISSN&#;X. PMC&#; PMID&#;
  2. ^ abcdefghijEyal N, Lipsitch M, Smith PG (31 March ). "Human challenge studies to accelerate coronavirus vaccine licensure". The Journal of Infectious Diseases. (11): – doi/infdis/jiaa PMC&#; PMID&#;
  3. ^ abcdefghijCallaway E (April ). "Should scientists infect healthy people with the coronavirus to test vaccines?". Nature. (): BibcodeNaturC. doi/d PMID&#;
  4. ^Balasingam, S; Horby, P; Wilder-Smith, A (September ). "The potential for a controlled human infection platform in Singapore". Singapore Medical Journal. 55 (9): – doi/smedj PMC&#; PMID&#;
  5. ^Cohen, Jon (18 May ). "Studies that intentionally infect people with disease-causing bugs are on the rise". Science. doi/science.aaf
  6. ^ abcd"Key criteria for the ethical acceptability of COVID human challenge studies"(PDF). World Health Organization. 6 May Retrieved 18 May
  7. ^ abcdCohen, Jon (31 March ). "Speed coronavirus vaccine testing by deliberately infecting volunteers? Not so fast, some scientists warn". Science. doi/science.abc S2CID&#; Retrieved 19 April
  8. ^"World's first coronavirus Human Challenge study receives ethics approval in the UK". GOV.UK. Retrieved 18 February
  9. ^ abWade Hemsworth (13 May ). "McMaster researcher contributes to WHO guidelines for COVID vaccine testing". McMaster University Medical School, Hamilton, Canada. Retrieved 25 May
  10. ^Eric Boodman (13 March ). "Coronavirus vaccine clinical trial starting without usual animal data". STAT. Retrieved 19 April
  11. ^Metzger, W. G.; Ehni, H.-J.; Kremsner, P. G.; Mordmüller, B. G. (). "Experimental infections in humans—historical and ethical reflections". Tropical Medicine & International Health. 24 (12): – doi/tmi ISSN&#; PMID&#;
  12. ^Gordon, SB; Rylance, J; Luck, A; Jambo, K; Ferreira, DM; Manda-Taylor, L; Bejon, P; Ngwira, B; Littler, K; Seager, Z; Gibani, M; Gmeiner, M; Roestenberg, M; Mlombe, Y; Wellcome Trust CHIM workshop, participants. (). "A framework for Controlled Human Infection Model (CHIM) studies in Malawi: Report of a Wellcome Trust workshop on CHIM in Low Income Countries held in Blantyre, Malawi". Wellcome Open Research. 2: doi/wellcomeopenres PMC&#; PMID&#;
  13. ^ abBinik, Ariella (May ). "What risks should be permissible in controlled human infection model studies?". Bioethics. 34 (4): – doi/bioe PMID&#; S2CID&#;
  14. ^D, Sinclair; K, Abba; K, Zaman; F, Qadri; PM, Graves (16 March ). "Oral vaccines for preventing cholera". The Cochrane Database of Systematic Reviews (3): CD doi/CDpub2. PMC&#; PMID&#;
  15. ^Waddington, Claire S.; Darton, Thomas C.; Woodward, William E.; Angus, Brian; Levine, Myron M.; Pollard, Andrew J. (1 May ). "Advancing the management and control of typhoid fever: A review of the historical role of human challenge studies". Journal of Infection. 68 (5): – doi/j.jinf ISSN&#; PMID&#;
  16. ^ abcdeJ, Tuju; G, Kamuyu; Lm, Murungi; Fha, Osier (1 October ). "Vaccine candidate discovery for the next generation of malaria vaccines". Immunology. (2): – doi/imm PMC&#; PMID&#;
  17. ^Osowicki, Joshua; Azzopardi, Kristy I.; McIntyre, Liam; Rivera-Hernandez, Tania; Ong, Cheryl-lynn Y.; Baker, Ciara; Gillen, Christine M.; Walker, Mark J.; Smeesters, Pierre R.; Davies, Mark R.; Steer, Andrew C. (13 February ). "A Controlled Human Infection Model of Group A Streptococcus Pharyngitis: Which Strain and Why?". mSphere. 4 (1): e–18, /msphere/4/1/mSphere–atom. doi/mSphere PMC&#; PMID&#;
  18. ^McShane, Helen (15 May ). "Controlled Human Infection Models: Is it Really Feasible to Give People Tuberculosis?". American Journal of Respiratory and Critical Care Medicine. (10): – doi/rccmED. PMC&#; PMID&#; S2CID&#;
  19. ^MacLennan, Calman A; Aguilar, Anastazia Older; Steele, A Duncan (9 December ). "Consensus Report on Shigella Controlled Human Infection Model: Introduction and Overview". Clinical Infectious Diseases. 69 (Supplement_8): S–S doi/cid/ciz PMC&#; PMID&#;
  20. ^Merkel, Tod J (11 July ). "Toward a Controlled Human Infection Model of Pertussis". Clinical Infectious Diseases. 71 (2): – doi/cid/ciz PMC&#; PMID&#;
  21. ^Rose, Anuradha; Sekhar, Amrita (July ). "Bioethics of establishing a CHIM model for dengue vaccine development". International Journal of Infectious Diseases. 84: S74–S doi/j.ijid PMID&#;
  22. ^ abcdPlotkin, Stanley A.; Caplan, Arthur (20 April ). "Extraordinary diseases require extraordinary solutions". Vaccine. 38 (24): –8. doi/j.vaccine PMC&#; PMID&#;
  23. ^"UK plan to be first to run human challenge Covid trials". BBC News. 20 October

External links[edit]

Sours: https://en.wikipedia.org/wiki/Human_challenge_study

Defining a Human Challenge Trial

Clinical Researcher—May (Volume 34, Issue 5)

PEER REVIEWED

Seema Garg, MS, MBA, CQA, CSSGB

 

In light of the current COVID crisis, we are seeing an intense focus on the question of how soon we can make a vaccine available to protect the public from the novel SARS-CoV-2 coronavirus. Typically, developing a vaccine against any illness can take years and millions of dollars, and in some cases we still may not have complete success. For example, we have a vaccine for influenza, but it is not a universal vaccine; there is no vaccine for HIV, even after decades of research.

The last global pandemic was the H1N1 influenza (flu) pandemic. The first H1N1 case detected in United States was in April , and by June 11 the World Health Organization (WHO) signaled that a global pandemic of H1N1 influenza was under way. On July 23, the U.S. Food and Drug Administration’s (FDA’s) Vaccine and Related Biological Advisory Committee indicated agreement with the agency’s proposal to license a H1N1 vaccine candidate via a “strain change” pathway, and this was only possible because already-approved influenza vaccines existed for other strains of influenza virus, which unfortunately is not the case with the current COVID pandemic. On September 15, , FDA approved four vaccine candidates for H1N1 influenza and on November 16, , approval was granted for a fifth vaccine.{1}

So, what could expedite the development a vaccine against COVID? One tool in the research community’s toolbox is known as the human challenge trial (HCT). Open Orphan, a European clinical research organization, has launched a human coronavirus challenge study model aimed to guide and test the efficacy of new and existing vaccine candidates for COVID{2}

According to the WHO, HCTs are “trials in which participants are intentionally challenged (whether or not they have been vaccinated) with an infectious disease organism. This challenge organism may be close to wild-type and pathogenic, adapted and/or attenuated from wild-type with less or no pathogenicity, or genetically modified in some manner.”{3}

Essentially, in a typical Phase I trial, new drugs or vaccines are tested in healthy volunteers to determine the safety of the investigational product; the subjects are only given the drug or the vaccine that is being studied—they are never intentionally administered the disease-causing agent. In the case of an HCT, the healthy volunteers are administered the disease-causing agent to study their reactions to it. Depending on the design of the HCT, the healthy volunteer may or may not be administered a protective drug or vaccine before or after administration of the disease-causing agent.

The purpose of an HCT is the same as that of animal challenge studies and models, with the added advantage of studying the potential drug/vaccine candidates directly in humans in a controlled environment. This allows the research community to screen potential drug/vaccine candidates and move the most promising candidates to larger trials.

The advantage of an HCT over an animal challenge study is the speed it offers for identifying a good drug/vaccine candidate. Typically, when drug/vaccine candidates are studied in several different species of animals, the results are extrapolated to how these drug/vaccine candidates can be effective in humans and then tested in volunteer participants.

Not all drug/vaccine candidates that show promise in animal studies produce successful results in Phase I studies. With an HCT, the effectiveness of a drug/vaccine candidates that shows promise can be determined much faster. The new drug/vaccine candidates still have to go through the routine Phase I, II, and III trials, but the speed of taking a drug/vaccine candidate from the lab to Phase I trials can be cut significantly with HCTs.

Is it ethical to administer a healthy individual with disease-causing agent? After all, the Declaration of Helsinki states: “The health of my patient will be my first consideration”{4} and “While the primary purpose of medical research is to generate new knowledge, this goal can never take precedence over the rights and interests of individual research subjects.”{4}

By and large, the clinical research community has reached a consensus that, with proper oversight, it is ethical to conduct HCTs when they offer the greatest chance for rapid development of much-needed treatments. The argument is that HCTs can screen potentially effective drug/vaccine candidates in a much more controlled in-patient setting and with a much lower number of participants compared to routine testing in much larger populations. The early safety-determining advantages of this tactic extend into the somewhat less controlled environments of Phase II and III trials.{5}

So, one could argue that it is better to generate initial effectiveness data in small populations—and in a controlled setting—than to expose large populations to the potential drug/vaccine candidates in a less controlled environments. You might call this a “do less harm” kind of policy, and of course it can save time and money in critical healthcare situations.

What you need to conduct an HCT depends on what kind of challenge agent is being studied. There are no special requirements as far as U.S. regulations are concerned, but there are many guidance documents on the topic issued by different agencies and regulatory bodies. The most prominent guidances are the ones issued by Centers of Disease Control (CDC) on the topic of infection control, since most challenge agents being studied will be infectious organisms.

Some of the guidance documents issued by the CDC are on general infection prevention and some are specific to the organisms/disease being handled. An important page to bookmark for these guidance documents is https://www.cdc.gov/infectioncontrol/guidelines/index.html.{6} You can find infection control guidelines on activities ranging from basic disinfection and handwashing to preventing the spread of influenza and Ebola.

It is important to keep in mind that guidances issued by the CDC are not specifically about the conduct of HCTs, but they are for infection control within healthcare settings when caring for confirmed cases, probable cases, and cases under investigation for infection. However, these guidances can be applied depending upon the exact nature of disease agent a Human Challenge Unit plans to study.

A Human Challenge Unit is essentially a healthcare facility that handles patients with diseases—the only difference is that the unit knows what challenge agent it is studying at any given time, whereas a hospital must be always prepared for all common infectious agents. The premise of having the processes and systems for infection control, however, will be the same for both facilities. Some of the systems and processes for infection control that both type of facilities needs to include are:

  • Procedures for using personal protective equipment (PPE): gowning, gloving, masking before entering the areas where the infected patients/participants are housed and for de-gowning, de-gloving, and de-masking before the staff and/or other personnel leave these areas.{7}
  • Procedures to disinfect or sterilize medical waste before it leaves the facility, including used PPE.{8}
  • Procedures for movement in the facility: To reduce the potential for contamination, the facility should be designed for uni-directional movement; staff or patients/participants should move from low infection areas to high infection areas and not vice versa.{6}
  • Procedures for environmental infection control: The cleaning and disinfection of all items used in the Challenge Unit, including bed rails, tables, chairs, and other items that tend to stay in participants’ rooms, and things that are more mobile, like laundry, service utensils, etc. Everything must be treated as a potential infection carrier.{9}
  • Engineering controls: One of the most important infection control mechanism is the design of the facility and a facility’s ventilation system. There are many recommendations for how this should be done covering air flow, air exchanges, filters to be used in the ventilation systems, and whether the air should be re-circulated.{6}

All of this should be done based on what challenge agent the Challenge Unit plans to work with, so it is important to have agile facilities that can adapt to the different requirements of different organisms being studied. It is also important for the operational team to know the limits of its facilities and resources, and to never agree to study an organism that is incompatible with the biosafety level of the facilities. Know your expertise, but also know your limitations.

Challenge agents that have been or are being studied around the world include viruses, toxins, allergens, bacteria, and fungi. Some examples include studies on cholera{10} and influenza.{11} Many of these studies are listed on https://www.clinicaltrials.gov/ct2/home.

In the United States, challenge agents are considered to be drugs, and therefore the FDA has jurisdiction over the challenge studies. However, in the United Kingdom and European Union, the regulatory authorities do not consider challenge agents to be drugs.{12}

The FDA has included human challenge studies in its Guidance for Development of Vaccines to Protect Against Global Infectious Diseases, but has mostly said that study sponsors should discuss their development plan with the Center for Biologics Evaluation and Research prior to initiation of such studies.{13}

  1. The H1N1 pandemic: Summary Highlights, April –April https://www.cdc.gov/h1n1flu/cdcresponse.htm
  2. Open Orphan Launches World’s First Human Coronavirus Challenge Study. https://www.epmmagazine.com/news/worlds-first-human-coronavirus-challenge-study-model-launch/
  3. World Health Organization. Human Challenge Trials: Scientific and Regulatory Considerations. https://www.who.int/biologicals/expert_committee/Human_challenge_Trials_IK_final.pdf
  4. World Medical Association. WMA Declaration of Helsinki—Ethical Principles for Medical Research Involving Human Subjects. https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/
  5. Bambery B, Selgelid M, Weijer C, Savulescu J, Pollard A. Ethical Criteria for Human Challenge Studies in Infectious Diseases. Public Health Ethics 9(2). https://academic.oup.com/phe/article/9/2/92/
  1. Centers for Disease Control and Prevention. CDC Infection Control Guideline Library. https://www.cdc.gov/infectioncontrol/guidelines/index.html
  2. Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Healthcare Settings. https://www.cdc.gov/infectioncontrol/pdf/guidelines/isolation-guidelines-H.pdf
  3. Guideline for Disinfection and Sterilization in Healthcare Facilities, https://www.cdc.gov/infectioncontrol/pdf/guidelines/disinfection-guidelines-H.pdf
  4. Guidelines for Environmental Infection Control in Health-Care Facilities. https://www.cdc.gov/infectioncontrol/pdf/guidelines/environmental-guidelines-P.pdf
  5. Shirley D, McArthur M. The Utility of Human Challenge Studies in Vaccine Development: Lessons learned from Cholera. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC/
  6. Influenza human challenge study begins at NIH-sponsored clinical trial units. https://www.nih.gov/news-events/news-releases/influenza-human-challenge-study-begins-nih-sponsored-clinical-trial-units
  7. Catchpole A, Fullen D, Noulin N, Mann A, Gilbert A, Lanbkin-Williams R. The Manufacturing of Human Viral Challenge Agents for Use in Clinical Studies to Accelerate the Drug Development Process. BMC Research Notes https://bmcresnotes.biomedcentral.com/articles//s
  8. Guidance for Industry: General Principles for the Development of Vaccines to Protect Against Global Infectious Diseases. https://www.fda.gov/files/vaccines,%20blood%20&%20biologics/published/Guidance-for-Industry&#;General-Principles-for-the-Development-of-Vaccines-to-Protect-Against-Global-Infectious-Diseases.pdf

Seema Garg, MS, MBA, CQA, CSSGB, is a Principal Quality Assurance Auditor in Ashburn, Va.

Sours: https://acrpnet.org//05/12/what-is-a-human-challenge-trial-and-how-does-it-expedite-vaccine-development/

Wiki human challenge trials

Explained: What are human challenge trials, and why are they controversial?

The method, which involves intentionally infecting volunteers with the novel coronavirus, is being promoted in order to “speed up” the process of preparing a vaccine.

How are vaccines usually developed?

In most regulatory regimes, vaccines take several years to develop, and their development typically proceeds through three phases of clinical trials.

https://images.indianexpress.com//08/1x1.png

In Phase 1, small groups of people receive the trial vaccine. During Phase 2, the clinical study is expanded and the vaccine is given to people who have characteristics (such as age and physical health) similar to those for whom the new vaccine is intended.

In Phase 3, the vaccine is given to several thousand people and tested for efficacy and safety. During this phase, participants either receive the vaccine or a placebo. The efficacy of the vaccine is determined by comparing the prevalence of infection in the group that was administered the vaccine with the one which received a placebo. The hypothesis that those in the vaccine group will be infected significantly less is thus tested.

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What are human challenge trials?

Under human challenge trials, participants of both the vaccine group and placebo group upon consent are deliberately exposed to the infection – thus are “challenged” by the disease organism.

Proponents of the method believe that such trials could save valuable time in developing a Covid vaccine, as researchers would not have to wait for participants to contract the infection under real-world conditions.

A paper released on March 31 in The Journal of Infectious Diseases by researchers Nir Eyal, Marc Lipsitch, and Peter G Smith has proposed replacing Phase 3 with human challenge trials.

The paper said, “Controlled human challenge trials of SARS-CoV-2 vaccine candidates could accelerate the testing and potential rollout of efficacious vaccines. By replacing conventional Phase 3 testing of vaccine candidates, such trials may subtract many months from the licensure process, making efficacious vaccines available more quickly.”

According to experts, such testing would also require significantly less number of people than regular Phase 3 trials, which require thousands of volunteers.

As per the 1DaySooner website, “&#; by gathering detailed data on the process of infection and vaccine protection in a clinical setting, researchers could learn information that proves extremely useful for broader vaccine and therapeutic development efforts. Altogether, there are scenarios in which the speed of HCTs and the richness of the data they provide accelerate the development of an effective and broadly accessible Covid vaccine, with thousands or even millions of lives spared (depending on the pandemic’s long-term trajectory).”

Explained: What are human challenge trials, and why are they controversial? Human challenge trials: Proponents of the method believe that such trials could save valuable time in developing a Covid vaccine. (File Photo)

Human challenge trials: The ethical concerns

While human challenge trials are not new, they are usually carried out in developing medications for diseases which are considered less lethal and have been better understood by scientists over the years, such as malaria.

Critics have questioned undertaking such trials for Covid, a potentially deadly disease for even those who are less at risk, and which researchers are still in the early stages of studying.

In a document titled ‘Human Challenge Trials for Vaccine Development: regulatory considerations’, the World Health Organization (WHO) stated: “Human challenge studies have been conducted over hundreds of years and have contributed vital scientific knowledge that has led to advances in the development of drugs and vaccines. Nevertheless, such research can appear to be in conflict with the guiding principle in medicine to do no harm. Well documented historical examples of human exposure studies would be considered unethical by current standards. It is essential that challenge studies be conducted within an ethical framework in which truly informed consent is given.

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“When conducted, human challenge studies should be undertaken with abundant forethought, caution, and oversight. The value of the information to be gained should clearly justify the risks to human subjects. Information to be gained should clearly justify the risks to human subjects,” it added.

Sours: https://indianexpress.com/article/explained/human-challenge-trials-explained/
The Ethics of Human Challenge Trials During Covid-19

Challenge studies of human volunteers: ethical issues

There is a long history of medical research that involves intentionally infecting healthy people in order to study diseases and their treatments. Such research&#x;what might be called "human challenge studies"&#x;are an important strand of much current research&#x;for example, in the development of vaccinations. The many international and national guidelines about the proper conduct of medical research do not specifically address human challenge studies. In this paper we review the guidelines on the risk of harm that healthy volunteers may be exposed to in the course of medical research. We examine the ethical arguments that are implicit or explicit in these guidelines. We then ask whether there is reason for limiting such studies on grounds independent of risk of harm. We conclude that the major ethical concern with challenge studies is that of risk of harm and that the fact that a study is a challenge study is not a wrong in itself.

Sours: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC/

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