AIDS vaccine trials in India: ethical benchmarks and unanswered questions

[Guest guest]

AIDS vaccine trials in India: ethical benchmarks and unanswered

questions

Editorial: Indian Journal of Medical Ethics: Vol IV No 1 January-

March 2007

AMAR JESANI1, LESTER COUTINHO 2

1Coordinator, Centre for Studies in Ethics and Rights (an institute

of Anusandhan Trust), 4th .oor Candelar, 26 St Baptist Road,

Bandra West, Mumbai 400 050 INDIA e-mail: amar.jesani@...

2Country programme advisor (India), Packard Foundation. e-mail:

lcoutinho@...

Vaccines have fascinated public health and clinical practitioners

since Jenner's experimental inoculation of a young boy,

Philip, using cowpox blisters of the hand of Nelmes, a dairy

worker. Less than 50 years later vaccination became the preferred

method of combating smallpox in Britain and its empire, and the race

to develop new vaccines against other diseases ensued.

The fascination with vaccines gripped the scientific community and

also shaped the social imagination with the vision of a world free of

disease. This led to scientists experimenting not only on vulnerable

subjects like children, prisoners and the poor but also on

themselves. Indeed, in the early years of vaccine development,

ethical considerations and the human rights of individuals and groups

being experimented upon were sometimes given less importance.

Enmeshed in this indifference to human rights is the history of

colonialism and racism.

Although the Nuremburg Trial and the Code that emerged from its

judgment represent a watershed in the development of ethical

guidelines and regulations, the abuses and scandals did not cease.

Subsequent generations have made attempts to reassess history.

They have critiqued violations and strived to apply higher standards

of human rights and ethics in medical and vaccine research, to the

extent that these concerns take precedence over the potentials of

scientific discoveries.

AIDS vaccine research

The fact that HIV compromises the same immune system that is needed

for an effective vaccine, the variations in sub-types of the virus,

the difficulties and cost of HIV treatment and management and the

acute social stigma attached to the condition have posed challenges

to basic vaccine science as well as to the standards of care needed

during research. These in turn have affected the socio-economic

commitment needed to develop and, potentially, to use preventive

vaccines against HIV/AIDS. The situation is further complicated by

the fact that early estimations and projections of the course of the

HIV epidemic in developed countries are now being questioned

following evidence that public health interventions without vaccines

have slowed down the epidemic considerably. A similar situation is

now being projected for India, even though there has been no

definitive evidence of this so far.

In India, during the last two years, two preventive Phase I AIDS

vaccine trials have been launched, the first at the National AIDS

Research Institute (NARI) in Pune and the second in Chennai at the

Tuberculosis Research Centre in collaboration with the

nongovernmental organization YRG-Care.

However, unlike what happened in Uganda or Thailand, both trials have

steered clear of significant national and international controversy.

They therefore need to be assessed in terms of the gains made in

ethical standards as well as some challenges that need further public

discussion.

AIDS vaccine trials in India and ethical benchmarks

While one may disagree with the decision by the political

establishment and by scientific institutions to provide higher

priority to investment in AIDS vaccine trials, one must acknowledge

certain achievements in raising standards of ethics in the

preparation and conduct of clinical trials. It does not matter if

such standards were established due to pressure from activists or the

international community.

The preparatory process for the AIDS vaccine trials was regularly

reported in the media. Strategic attempts were made to evolve

a " political will " by involving some members of parliament, the Prime

Minister's office and the President. Efforts were also made to

involve persons with various professional expertise in periodic

consultations through an advisory body; some of these contributed

actively to laying down the informed consent process. And lastly, at

both the trial sites, there was an attempt to ensure greater local

involvement through community advisory boards.

The informed consent and participant information documents were

drafted using the inputs of diverse stakeholders and experts.

It was ensured that all known risks were clearly disclosed and the

right to withdraw from the trial at any stage was made very explicit.

Several other issues were addressed as well. Thus guidelines for

recruitment were developed to exclude the possibility of coercion and

gender imbalance; a recommendation was made to recruit educated

persons through public advertisements; a test of comprehension was to

be administered; and, to avoid the possibility of undue financial

incentive, a standard nominal reimbursement of expenses for each

visit was fixed for all participants.

Participants who became HIV positive during the trial would receive

free access to care, support and treatment, including anti-retroviral

therapy, for five years, and an assurance was given that continued

access would be advocated for. The sponsor insured all participants

for care, treatment and compensation for trial related injuries. An

independent arbitration board was created to redress trial-related

complaints, and this included compensation for injuries and the care

of participants who become HIV positive. A stipulation was laid down

that the ethics committee and the arbitration board's recommendations

would be respected.

Although there is no independent assessment available on the extent

to which these standards were actually implemented during the trials,

the fact that all sponsors agreed to these standards has established

a benchmark for all clinical trials taking place in the country.

Some critical issues for discussion

Before conducting any clinical trial, it is essential to consider

whether there is a strong justification for exposing participants to

the risks of the trial. Some doubts still persist about the

justification for the hasty beginning of the first Phase I trial at

the NARI of the tgAAC09, a recombinant adeno-associated viral vector-

based candidate vaccine.

Phase I trials of the tgAAC09 vaccine had started in December 2003 in

Belgium and Germany and their results were awaited in early 2005.

Instead of waiting for these results, a trial of the same candidate

vaccine, with the same protocol, was started in India on February 7,

2005. On February 22, barely two weeks after the trial was launched

in India, Targeted Genetics, the company conducting

the trials in collaboration with the International AIDS Vaccine

Initiative (IAVI), issued a press statement announcing the

preliminary results of the Belgium-Germany trials. It stated: " The

Phase I trial is primarily designed to evaluate safety and

tolerability of the vaccine at escalating dose levels. The study is

also designed to evaluate immune responses following vaccination. No

safety concerns were identified and the vaccine at the doses

evaluated was well tolerated. In addition, a single administration of

the vaccine at the doses evaluated in this initial study did not

elicit significant immune responses. " (1)

Since the overseas sponsors of the India trials, IAVI and Targeted

Genetics, were also involved in the Belgium-Germany trials, it is

inconceivable that they did not know of the latter's preliminary

findings two weeks before the extension of that trial in India.

Did they share this information with the Indian sponsors – the Indian

Council of Medical Research, the ministry of health and family

welfare and the National AIDS Control Organization? Did the Indian

sponsors ask to examine the data of the Belgium-Germany trials before

commencing the trial of the same vaccine in India? This apparent lack

of communication raises questions on the nature of the partnership

between the Indian and overseas partners. It may be argued that even

if India was to eventually conduct a Phase II trial of the same

candidate vaccine with a different dosage, a Phase I would still be

necessary. But would a more detailed analysis of the data prior to

the Indian trial have resulted in a radically altered Phase I

protocol here?

Under the circumstances, the sponsors in India were compelled to make

amendments -- including amending the informed consent form to give

information on the results of the Belgium-Germany trial to

participants -- a few months after the trial started.

A related question pertains to the complete absence of a " political

and scientific will " to systematically develop and test therapeutic

vaccines. This is perhaps an inadvertent outcome of depending on a

single sponsor. The therapeutic vaccine would pose fewer ethical

challenges. The scientific challenges may be comparable but it would

cost less to vaccinate infected persons alone, rather than an entire

population. Why is this option kept out of the policy debate?

The field of vaccine development today is driven not entirely by

altruistic motives. It is shaped as much by philanthropy as by

competitive market interests, global institutional arrangements of

intellectual property rights, patents, scientific capacities (or the

lack thereof ), and the interests of investors and shareholders.

Hence, another critical area that needs public debate is the

arrangement between the company holding patents of the candidate

vaccines and the government. It is essential that only those

candidate vaccines are tried whose technology will be transferred to

the host country, with the commodity to be made available at a price

that the country can afford. In the absence of specific agreements

and mechanisms for accountability even a successful trial may not

necessarily benefit the country.

Conflict of Interest: Amar Jesani is a member of the advisory group

of IAVI and Lester Coutinho was formerly a consultant with IAVI.

Reference

1. Targeted Genetics Corporation [homepage on the internet]. Targeted

Genetics announces preliminary safety data from phase I HIV vaccine

trial. [cited 2007 Jan 8]. Available from:

http://ir.targen.com/phoenix.zhtml?c=84981 & p=irol-

newsArticle & ID=677299 &

Indian Journal of Medical Ethics Vol IV No 1 January-March 2007