Amar JesaniIndian Journal of Medical Ethics (www.ijme.in) Centre for Studies in Ethics and Rights (www.cser.in) Mumbai, India

Bioethics as health activism I have taken public position on the

case around which this presentation is structured

I was also a member of the advisory committee of the project for a brief while – after the data of the formative research came in, and participated in the committee to discuss draft report. However, soon after I resigned from the committee.

Framework About India A case study of HPV vaccine demonstration

project Learning from the case

(a) Science and evidence (b) Coming together of global policy makers (c) Promotion of techno-managerial solutions in public

health (d) Nation state: What is the right balance between

facilitation and regulation? (e) Global health governance: Is there a balance

between facilitation and regulations? To conclude

The global health policies are increasingly shaped by (a) global trade relations giving priority to the

interests of global Corporate business, (b) World bank’s involvement in the field of

health and (c) Private philanthropic foundations

The inter-governmental agency, the WHO, has considerably ceded its powers in the global governance to the above players

Global health policies are paying only lip service to strengthening of the national public health system

Dominant disease centric vertical approach is often found to weaken the existing health systems in many developing countries

The non-state players dominate in setting the agenda and priorities, and they often co-opt the national elites in the process

The international community must learn from the experiences of the global health policies in the field

Policies without robust global and national governance systems would not provide expected results

High economic growth of last two decades Booming business – including private for-

profit pharmaceutical and hospital service sectors

Massive export of drugs, and country opened to Medical tourism and Clinical trials to sustain health care business

At the same time Increased inequities - Substantial proportion

of population below poverty line, illiterate or semi-literate, and discrimination in accessing health care

Government spends only ONE percent of GDP on health care, which is one fifth or sixth of total health care expenditure

No universal access to health care 80% of health services in for-profit private sector 10-20% covered under voluntary health insurance High cost of health care & over two third of

health care financed by out of pocket expenditure by patients

Cost of health care a major cause of poverty Recent report for universal access system

Health care regulations: Dominant for-profit private health sector covered

under grossly inadequate regulations . Existing weak regulations hardly implemented

Instead of putting together evidence from the review of scientific literature, this presentation takes up a case and tries to unravel the effect of the global health policies at the ground level in India.

It argues that the complexities should not deter us from understanding something very simple that emerges from the analysis of practice

Cervical cancer - a major cause of deaths of women due to cancer. Also has a history of unethical research in India

Screening program 1976 to 1990: A long term observational study of

1163 women with cervical dysplasia to understand causative factors and biological behaviour of dysplasia.

Rationale – scarce resources could be saved if dysplasias that need intervention are identified

This research was completely supported from Indian sources and Indian medical scientists and institutions were involved

The end point of the study was carcinoma in situ (CIS) when appropriate treatment was offered.

In 1986, the results of the study were extensively used in planning National Cancer Control Program for control of cervical cancer.

However, the screening program could never be universalised due to low investment and weak public health system

So the very purpose with which over a thousand women were exposed to risks without offering treatment was never achieved

Controversy in 1997

HPV vaccine• 2006-07: Phase IIIb marketing approval clinical trials

of the HPV vaccines to test its immunogenicity in 100 to 200 subjects

• 2008: Marketing approval by Indian drugs regulator• 2009: Market launch of vaccineHPV vaccine demonstration project• 2007: PATH, in collaboration with Indian Council of

Medical Research (ICMR) and two state governments (Andhra Pradesh and Gujarat) launched the project – funded by the Gates Foundation

• Objective: “generating evidence the would enable policy makers to decide on possible public sector introduction of the HPV vaccine” in the country’s immunisation program

HPV vaccine demonstration project• 2008: Completion of formative research in one district

each of two states• 2009: Launch of demonstration project with two

components: • (a) An observational study of post-licensure HPV

vaccination (a Phase IV clinical research on a vaccine)

• (b) Evaluation of Implementation of HPV vaccination though operational research in terms of coverage, acceptability, feasibility and costs.

• Of the five primary outcome measures, four were assessment of serious and non-serious adverse events and the timeliness of their reporting

• The Companies, the producers of the vaccines, provided vaccine free for the study (costing over $5 million)

2010: After 23,428 girls in the age group 10 to 14 years were vaccinated, in March it was suspended following an investigation report by women’s health organisation, Sama, Delhi, on the death of seven girls (5 in AP, and 2 in Gujarat)

2010, April: Govt appointed an Investigation Committee

Committee submitted its final report on February 15, 2011

The report is still not in public domain, but its interim report released on Nov 10, 2010 is in public domain

The report points to several concerns which are important for their human rights and public health dimensions – so also for the Global Health Policies

Some of the findings of the committee: The project, though used the national

immunisation services, was never put up for appraisal by the National Technical Advisory Group on Immunisation

A quarter of participants were drawn from tribal communities In the predominantly tribal blocks it was known that

the immunisation system was not in robust shape, with extremely inadequate reporting and management of the Adverse Event Following Immunisation (AEFI)

And yet the project relied on it without enhancing its capacity, or creating additional support structure from the project.

As a consequence, non-serious adverse events hardly got recorded (0.29% to 1.37%), and there were long delays in reporting of serious adverse events

In AP, the deaths of girls who died in July, Sept and Oct 2009, were not taken cognizance until Jan 29, 2010.

In the process, the project also blurred the distinction between regular work of the national immunisation program and the research project

Gave a wrong impression to people that the HPV vaccine was a part of the national program

Deficiencies in Informed consent: • (a) In AP, 20% parents gave thumb impression, • (b) In Gujarat, 37% parents gave thumb

impression• (c) The AP tribal department issued an

administrative order giving authority to hostel warden/head masters of schools to provide consent on behalf of girls - nearly one-third of forms were signed by them

• (d) a sample study of the forms found most of the forms deficient in information, many names not matching with the signatures,

▪ (e) assent of girls not documented, though as per the ICMR guidelines, it is mandatory to do so

• (f) at no time the participants were provided information that the HPV is a sexually transmitted infection; and not told about other preventive measures available

No insurance for participants obtained, though insurance for PATH and its researchers was purchased.

Since project did not have its own follow up mechanism, no appropriate data on causality of girls’ death were available, but indirect evidence suggested that deaths were not related to the vaccine. No compensation paid.

What do we learn from this case?

Prima facie, the researchers involved in the project believed that once a good tool is developed by the science, the only thing remaining for its use is to show that it can be delivered – nothing else mattered

Evidence is not evidence without a proof from experiment – a wholesale application of the natural science paradigm to the social reality

Under development of developing societies converted into disease emergencies

In the “war on terror”, the doubters are unpatriotic; in the “war on disease”, they are “against science”!

Societies and communities are emerging as a vast terrain for experimentation – the experiments are getting converted into “experimentality”.

Social experiments are good when they are needed, if Undertaken with some credible consent of communities and

individuals involved, and protection of their safety And there is economic feasibility and political will to

implement their findings. At present, social and public health experiments are

global trends, involving researchers from all types of nations

And yet, we do not have ethical framework and guidelines in place for protection of participants’ human rights

The project brought together most of the key players of the global health: An international foundation set up for philanthropy An international NGO established to do research on

technologies - an NGO that acted more like a Contract Research Organisation

The pharmaceutical companies that donated over $5 million dollar worth vaccines with an eye on a massive captive market

A willing national scientific establishment that was more interested in experiment than the feasibility of providing universal access to the benefits of its findings to the people

And interestingly, the WHO Bulletin was the first to publish the findings of operation research without any mention of what happened in that research in India

This, indeed, was a big global collaborative research taken with an obvious objective of impacting a nation’s public health system.

Yet, the investigation committee or the research ethics committees that reviewed the project, were not provided any information on: Total cost involved Terms of agreements and contracts signed by all

participating parties All parties invoked “trade secret” clause of

India’s Right to Information Law when they were formally requested by the civil society organisation to reveal those agreements and research protocol used

Thus, the operation of the international and national health policy makers is shrouded in complete secrecy

The formal release and public discussion of the investigation committee report are stalled, as government has taken no action on its findings

Not just hard-core biomedical research for commercial product development, but also the social research with potential to affect lives of millions of people, is a part of the trade policies, and secrets that surround them

A section of scientific, bureaucratic, corporate and political elite at national level is always implicated to ensure that if anything went wrong, there will be the least repercussion

Lastly, something about the involvement of philanthropic organisations in international and national health policies

What should be the role of such foundations? Should their dominant actions be such that

consistently and progressively the health moves from the realm of market and philanthropy to human rights?

Should they narrowly concentrate on the task of plugging the market failures so that the rest of business and trade could go on unhindered?

There is a need to engage with private players, but the engagement ought to be for pulling them in towards the right to health

There is no doubt that the public health systems of many developing countries are deprived of basic technologies and suffer from inefficient and sometimes corrupt management practices

The building of universal access public health system with adequate technology and strong, transparent and accountable management system ought to be a top priority on the agenda of the global health policies

Social and public health research, therefore, need to be evaluated from the perspective of whether it would build a good health system or break the existing one, howsoever deficient it may be – the responsiveness requirement of ethics thus has a massive added dimension in such research

For this project, from the health system building perspective, there were two important questions: It is known that HPV vaccine will not provide

protection to a significant number of people (over two fifth of them). Would the research be done in communities where the

screening and treatment program is in place? Would the introduction of universal screening and

treatment program go hand-in-hand with the introduction of universal vaccination of girls?

How would the weak public health system accommodate the task of universal immunisation with one more vaccine?

And above all, how cost-effective would that be as compared to universal screening program that would build basic laboratory and medical services?

Social and public health experiments are often done with an intention to keep multiple solutions ready for the system as and when it is able to absorb their findings or, if the system cannot absorb them in foreseeable future, then at least some can avail of it from the market

When system is not ready, the use of its infra-structure for experimentation, more so if that would disrupt its normal functioning, must be critically examined

There is some lack of ethical responsiveness when experiments are done on the poor who are unlikely to afford when their findings are scaled up in the market

The clinical trials outsourced in developing countries, with research participants drawn from the poor communities lacking access to health care, have shown phenomenal lack of ethical responsiveness

The social and public health intervention research going in the same direction ought to worry all of us

Lastly, the international polio eradication program – another techno-managerial solution that disrupted regular health services for long - and with India declared free of polio cases, has raised concerns about the disease eradication strategies, and about the Non Polio Flaccid Paralysis cases getting neglected in the health system

The HPV vaccine project would not have been possible within the public health system without the helping hand of the state

The reach of the global health players was such that they could obtain from the state an administrative order compromising rights of the participants

On May 8, 2012 the Parliament Standing Committee in its report noted that the stated mission of the Indian drugs regulator is “to meet the aspirations... demands and requirements of the pharmaceutical industry”, without any reference to protection of consumers and research participants.

Report provides numerous instances of drugs approved for marketing without adequate research and the industry drafting and obtaining support from doctors on identical letters of recommendation to get drugs approved

Regulatory agencies are grossly under-staffed, poorly trained in inspection and monitoring and lack competence to scientifically evaluate research findings

If a similar investigation is done of research ethics committees - the frontline regulators of clinical health research going on in over 4000 hospitals and research institutions in India – its findings would be similar

Capture of regulators by the regulated is not new – but the concern is that the national and international health policies are the least committed to change the situation

There is inadequate material and human investment and capacity building for regulations

Good governance is not possible without independent, transparent and accountable regulators

The physical independence of regulators may have to go hand-in-hand with the political and ideological liberation from the deep rooted convictions of theirs that limit their actions to facilitation without effective protection of users of services and research participants

The situation in the global health governance in some ways mirror the situation at the national level in some developing countries

The dominant players in the global policies on trade, services and research in health are effectively allowed to decide the system of governance themselves.

The inter-governmental agency, the WHO as a UN body is reduced to a technical organisation without power in the global governance

A huge proportion (nearly 80%) of funding of the WHO comes from the partnerships it forges with the global health players – aid funds of member states, corporate sector, philanthropic foundations and the banking institutions

Such funding is conditional, short-term extra-budgetary funds

This compromises its constitutional mandate as against the specific interests and priorities of individual donors

Unlike the WTO, the WHO has no mandate to work for compulsory dispute settlement and enforcement

We may get carried away by the complexities of global health policies, and conclude that there are no easy solutions

Or we may take a view that complexities should not deter us from finding the basic political trends that become easily visible when the complex policies are seen from what is happening at the ground level

To make global health policies useful for developing countries and to establish and strengthen universal access health care systems, we need to evolve independent, transparent and accountable governance, globally as well as nationally.

Marchal Bruno et al, “Global health actors claim to support health system strengthening: Is this reality or rhetoric?” PLoS, 2009, 6(4)

Sarojini NB et al, “HPV vaccine: science, ethics & regulation”, 2010, EPW, 45(27): 27-34. Sarojini NB et al, “Undeniable violations, unidentifiable violators”, 2011, EPW, 46(24): 17-19)

Amit Sengupta, “Global governance of health: a minefield of contradictions and sectional interests, Ind Jn of Med Ethics, 8(2): 86-90 (www.ijme.in)

Reports of Global Health Watch, 2005, 2008, 2011 Report of the High Level Committee on Universal

Health Coverage, Planning Commission, India, 2011

Final report of the committee appointed by Govt of India to enquire into “alleged irregularities in the conduct of studies using HPV vaccine” by PATH in India, Feb 15, 2011

59th Report of the department related Parliamentary Standing Committee on functioning of the Central Drugs Standard Control Organisation, Government of India, May 2012

Neetu Vashisth, Jacob Puliyel, “Polio program: Let us declare victory and move on”, Indian Journal of Medical Ethics, Vol IX, No. 2; April-June 2012, pages 114-117