Ethical Issues in HIV Vaccine Trial (Display)

7/31/2019 Ethical Issues in HIV Vaccine Trial (Display)

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ETHICAL CONSIDERATION IN

INTERNATIONAL HIV

VACCINE TRIALS

An Ethical analysis of HIV vaccine trials


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For the sake of clear and soundunderstanding of our discussion..

IMPORTANT TERMINOLOGIES


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TERMINOLOGIES

AIDS

VACCINE

VACCINE EFFICACY

PLACEBO

IMMUNOGENICITY

INCIDENCE

RISK BEHAVIOUR CANDIDATE VACCINE

VIRAL LOAD


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1. The HIV pandemic

Global prevalence of disease and death related to HIVis increasing at alarming rate

AIDS is now the major cause of death in Africa, and 4thworldwide

More than 16,000 HIV infections occur everyday The International AIDS Vaccine Initiative (IAVI)

projects that a vaccine with just 50% efficacyadministered to 30% of the population of developingcountries between 2015 and 2030 would preventapproximately a quarter of the infections that wouldotherwise occur.

Without a vaccine, the number of new infections peryear could increase from 6 million to 10 million by

2030.


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2. The inaccessibility to the mosteffective treatment

Antiretroviral Medication

Complicated to administer

Requires close monitoring

Causes adverse side effects

Extremely costly


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3. Burden of disease is greatest in

poorest countries More than 95% of all HIV infections occur in

developing countries

Of the 33.3 million people living with HIV/AIDSacross the world, 22.5 million are in Africa.

South Africa also has one of the highest

numbers of children under 15 living withHIV/AIDS in the world; estimates range from180,000 to 280,000.


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Pre-clinical Phase I Phase II Phase III

Phases of Testing and ClinicalTrials


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Pre-Clinical Trials

Animal trials are also known as pre-clinicaltrials. But no matter how much we learn andstudy in animal models, only people become

infected with HUMAN immunodeficiency virus.Since no animals have the same immunesystems as humans, the only way to prove avaccine's effectiveness is to test in people, so

ultimately we have to move forward into humantrials.


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Phase I Trials

Phase I trials are generally small (less numberof healthy, uninfected participants at low risk ofHIV infection than 100 participants) anddesigned to see if the vaccine is safe. Phase I

trials usually last 12-18 months.


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Phase II Trials

The goals of Phase II trials are usually to learnmore about vaccine safety and to see if thevaccine generates an immune response.

Phase II trials, which involve hundreds ofparticipants. Phase II trials can last 2 or moreyears.


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Phase III Trials

After a successful Phase II trial, a Phase III trialinvolves several thousand high-risk volunteersto further assess if the vaccine works in

preventing HIV infection. Phase III trials canlast 3-5 years.


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Suggested guidance

ETHICAL CONSIDERATIONS INHIV PREVENTIVE VACCINERESEARCH


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1. HIV vaccines development

Sufficient capacity and incentives should bedeveloped to foster the early and ethicaldevelopment of effective vaccines.


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2. Vaccine availability

Any HIV preventive vaccine demonstrated tobe safe and effective should be madeavailable as soon as possible to all

participants in the trials on which it was tested Plans should be developed at the initial stages

of HIV vaccine development to ensure suchavailability.


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3. Capacity building

Strategies should be implemented to buildcapacity in host countries and communities sothat they can practice meaningful self-

determination in vaccine development, canensure the scientific and ethical conduct ofvaccine development, and can function asequal partners with sponsors and others in a

collaborative process.


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5. Community participation

To ensure the ethical and scientific quality ofproposed research, its relevance to the

affected community, and its acceptance by theaffected community representatives should beinvolved in an early and sustained manner inthe design, development, implementations, and

distribution of results of HIV vaccine research


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6. Scientific and ethical review

HIV preventive vaccine trials should only be

carried out in countries and communities thathave the capacity to conduct appropriateindependent and competent scientific andethical review.


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7. Vulnerable populations

Where relevant, the research protocol shoulddescribe the social contexts of a proposedresearch population that create conditions for

possible exploitation or increased vulnerabilityamong potential research participants, as wellas the steps that will be taken to overcome the

and protect the dignity, safety , and welfare ofthe participants.


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8. Clinical trial phases

As phases |, ||, ||| in the clinical development ofa preventive vaccine all have their ownparticular scientific requirements and specific

ethical challenges, the choice of studypopulations for each trial phase should be

justified in advance in scientific and ethicalterms in all cases.


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9. Potential harms

The nature, magnitude and probability of allpotential harms resulting from participation inan HIV preventive vaccine trial should be

specified in the research protocol as fully ascan be reasonably done, including provisionfor the highest level of care to participants whoexperience adverse reactions to the vaccine,

compensation for injury related to the research,and referral to psychosocial and legal support.


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10.Benefits

The research protocol should outline the

benefits that persons participating in HIVpreventive vaccine trials should experience asa result of their participation.


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11. Control group

As long as there is no known effective HIVpreventive vaccine a placebo control arm

should be considered ethically acceptable in aphase ||| HIV preventive vaccine trial.

Placebo-controlled vaccine trials are ethically

acceptable as long as there is no knowneffective HIV preventive vaccine


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12. Informed consent

Independent and informed consent based oncomplete, accurate, and appropriately

conveyed and understood information shouldbe obtained from each individual while beingscreened for eligibility for participation in anHIV preventive vaccine trial, and before he/she

is actually enrolled in the trial.


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13. Informed consent specialmeasures

Special measures should be taken to protectpersons who are, or may be, limited in theirability to provide informed consent due to theirsocial or legal status.


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14. Risk-reduction interventions

Appropriate risk-reduction counseling and

access to prevention methods should beprovided to all vaccine trial participants, withnew methods being added as they arediscovered and validated.


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15. Monitoring informed consentand interventions

A plan for monitoring the initial and continuing

adequacy of the informed consent process andrisk-reduction interventions, includingcounseling and access to prevention methods,should be agreed upon before the trial

commences


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16. Care and treatment

Care and treatment for HIV/AIDS and itsassociated complications should be provided to

participants in HIV preventive vaccine trials,with the ideal being to provide the best proventherapy, and the minimum to provide thehighest level of care attainable in the hostcountry.


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17. Women

As women, including those who are potentiallypregnant, pregnant, or breast-feeding, should

be recipients of future HIV preventive vaccines,women should be included in clinical trials inorder to verify safety, immunogenicity, andefficacy from their standpoint.


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18. Children

As children should be recipients of future HIV

preventive vaccines, children should beincluded in clinical trials in order to verifysafety, immunogenicity, and efficacy from theirstandpoint.


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Challenges faced by researchers

DIFFICULTIES IN DEVELOPINGEFFECTIVE HIV VACCINE


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1. HIV is a retrovirus

its genetic information is contained in RNAinstead of DNA.

Currently, no vaccines against humanretroviruses exist, so researchers lack priormodels from which to work


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2. Antiretroviral drugs, the most effectivetreatment strategy currently available,decrease a patient's viral load and delay the

development of AIDS, but they do not eliminateHIV from the body. As a result, scientists haveno examples of successful immune responsesto guide them in vaccine development.


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3. Lack of suitable animal models on which totest vaccines before initiating trials withhumans. Experiments currently involve

chimpanzees infected with HIV and monkeysinfected with Simian Immunodeficiency Virus(SIV), a related virus. However, vaccinecandidates have invoked different responses in

each animal model.


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4. HIV's genetic variability and geographicaldistribution.

There are nine subtypes, of the virus. Virusesfrom different subtypes can recombine tocreate new hybrid viruses, known as circulating

recombinant forms (CRFs), which also infecthumans.

Subtypes and CRFs have differentgeographical distributions.

Scientists are not yet certain of the significanceof this genetic diversity, but it could mean thatdifferent vaccines would be needed for different

subtypes of the virus.


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5. Need to be conducted in populations with highincidence of HIV infections, namely developingcountries to produce valid and timely results


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ETHICAL ANALYSIS

1. Type of vaccine used

2. Standard of Care

3. Social Consequences

4. Conflicting interests

5. Enrolling vulnerable participants


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An ethical analysis

1. TYPE OF VACCINE USED


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TYPE OF VACCINE USED

Most scientists believe that using wholeinactivated or live-attenuated (weakened)viruses, cannot be employed for safety andethical reasons.

Experiments with primates showed that somemacaques who were given the candidatevaccine eventually developed an AIDS-like

syndrome. This suggested that the strains used in the

vaccines could be deadly to individuals with

immature immune systems.


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In trials of other vaccines, however, live-

attenuated vaccines against other infectionshave provided better protection of thoseimmunized because they can stimulate a moresubstantial and broad-based immune response

It can be argued that it would be permissible touse a live-attenuated HIV vaccine with thepotential to save millions of lives worldwide,

even if a comparatively small number of peoplewere at risk of infection from the vaccine itself


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An ethical analysis

2. STANDARD OF CARE


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STANDARD OF CARE

Inability of Worldwide, scientists, ethicists,research sponsors, and governments to reachconsensus

Many factors are considered when researchersexplore the provision of medical care during aclinical trial.

The situation is complicated further when

the disease is chronic

the trials are held in resource-constrainedenvironments


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PRO

it is morally unacceptable to allow patients toreceive less-than-optimal treatment

Rich countries sponsoring research in poorer

countries have greater access to resourcesand are therefore ethically obligated tocontribute to sustainable improvements in theoverall health of developing nations


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Generally, all parties believe that somemedical care beyond the specific requirements

of the research protocol should be provided toclinical trial participants. The majority opinion isthat because communities and individualsparticipating in trials "are contributing to

knowledge that is a global public good, [they]should benefit in return.

The issue is what level of care should be

provided, by whom, and for how long.


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AGAINST

1. One option is the provision of the best treatmentcurrently in existence worldwide - namely lifelonguse of antiretroviral drugs (ARVs)

As of 2006, the current cost of highly active

antiretroviral treatment (HAART), the standarddrug regimen for those infected with HIV, wasestimated to be $730 per patient-year

Clinical trials conducted in America or Europe

would require that infected participants receive thebest available care, a lifetime regimen of anti-retroviral drugs, but for similar trials held indeveloping countries, the prospect of such care is

dim at present.


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2. Treatment of HIV/AIDS is much more than

purchasing and supplying medications Frequent follow-up and monitoring of patients

are required

Developing countries and even clinical trialsites often lack the infrastructure

Once the trial ends and researchers return totheir home countries, ongoing treatment in the

host countries would have to be continued byanother entity


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3. Sharp decrease in the scientific community

(researchers)'s ability to conduct future HIVvaccine clinical trials.

Funding and infrastructure are insufficient

manufacturers' and other trial sponsors'incentives to conduct essential research indeveloping countries would quickly erode

High costs are likely to deter sponsors,

researchers, and local health authorities frominitiating innovative and more ambitiousprojects


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4. equity issues arises from provision oftreatment

Community and familial relations could becomestrained

the promise of superior medical care could

become an undue incentive

well-resourced, research-sponsored care in anotherwise impoverished healthcare facility is an

example of global health inequities.


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An ethical analysis

3. SOCIAL CONSEQUENCESOF HIV INFECTION


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Social effects of HIV vaccine

Some vaccine candidates may cause you toappear HIV positive

Volunteers may be falsely identified as HIV-

positive simply through association with trial

by developing falsely positive HIV antibody test

Volunteers will be counseled to only get HIVtesting at the trial site


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experienced discrimination when other knowthat they were participating

No medical side effects or problems areassociated with appearing HIV infected on

certain tests.

Participants will not be able to donate bloodand they may have a lot of difficulties


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An ethical analysis

4. Conflicting interests

Conflicts of Interest


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Conflicts of Interest

health care providers gain prestige, grants,and promotions through their research andpublication of their work. Accordingly, they

have a personal interest in recruiting andmaintaining participants in their studies.

some conflicting interests may influence thenumerous decisions researchers make over

the course of a study.
http://openwindow%28%27insite-kb-ref.jsp/?page=kb-08-01-05&rf=45,54%27,%27References%27)


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An ethical analysis

5. ENROLLING VULNERABLEPARTICIPANTS


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VULNERABLE PARTICIPANTS

Adolescents

participating age from 12 to18

Women


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1. Informed consent

2. Protected from harm

3. Right to withdraw

4. Privacy

5. Discrimination, violence, and social rejection


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Study case : Participation of Adolescents in

HIV vaccine trials in South Africa

OBSTACLES TOPARENTALCONSENT


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Obstacles to Parental Consent

Child-headed households

- orphans, children without resident adultguardians

Many of adolescents attending the prenataland family planning clinics dont live with

parents


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CONCLUSION


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CONCLUSION

CLOSING: Volunteers in clinical trialscannot get HIV infection or AIDS byreceiving an experimental vaccine.

An experimental vaccine must successfullycomplete at least three stages of testing inpeople before it can be licensed. Humanclinical trials are regulated by strict ethical and

scientific controls, and occur at specializedresearch centers around the world.

Ethical Issues in HIV Vaccine Trial (Display)

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