[e-drug] Fact check: HPV vaccine project in India

e-drug
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E-DRUG: Fact check: HPV vaccine project in India
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Dear e-drug readers:

There has recently been a post related to a TV newsmagazine segment about an HPV vaccine project in India. We would like to clarify some misinformation in that piece and provide further facts about the project:
http://www.path.org/news/an100422-hpv-india.php.

In that document you will see that:
To date, no reported deaths have been causally associated with HPV vaccination in India or
elsewhere. Experience with the HPV vaccines used in the PATH-ICMR
post-licensure observational study confirms the good safety profile reported in clinical trials.

The vaccines used in the study have been licensed by the Indian Government and are available in
the market in India and in many other countries. They are commercial products approved by the Drug Controller General of India (DCGI), US Food and Drug Administration (FDA), European
Medicines Agency (EMEA), and other national regulatory bodies.

The Federation of Obstetric and Gynaecological Societies of India (FOGSI)
and the Indian Academy of Pediatrics (IAP) recommend HPV vaccine, as does the World Health Organization (WHO) and many other agencies. The two HPV vaccines used in the project have been
prequalified by WHO.

As of December 2009, 28 high-resource countries, including the United States, Australia, and many European nations, have included HPV vaccination in their national immunization programs.The
post-licensure observational studies in India do not seek to evaluate the efficacy or safety of these licensed, approved HPV vaccines. No biomedical outcomes are being researched; no blood or other samples are being drawn, and no therapies are being tested.

Instead the project seeks to assess HPV vaccine coverage achieved, acceptability in the community,
feasibility, and cost of implementing HPV vaccination through different strategies.

The blocks (neighborhoods) used in the study were selected to represent diverse populations that would be eligible for HPV vaccination through a public health program, including those in urban, rural, and tribal settings. For approval of the post-licensure observational study, PATH and its Indian
collaborators worked with two ethical review committees in India and one in the United States to design study protocols and informed consent materials.

Thank you for your interest in cervical cancer prevention. By improving screening and treatment for
adult women, and introducing HPV vaccination for young adolescent girls, we can reduce the terrible burden of cervical cancer worldwide (~500,000 cancer cases ~270,000 deaths each year with 25% of
those deaths occurring in India alone).

The PATH Cervical Cancer Team
Program for Appropriate Technology in Health, (PATH)
PO Box 900922, Seattle, WA 98109 USA
Visit the RHO Cervical Cancer
Library at www.rho.org
S Wittet <sw7030@hotmail.com>

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E-DRUG: Fact check: HPV vaccine project in India (2)
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[There has been considerable discussion about the ethics of clinical trials in developing countries. It is worth looking through the e-drug archives. Moderator]

The TV programme on HPV vaccination among minor, mainly tribal drug-naive girls in India was investigated, produced and telecast by CNN-IBN, a highly respected, credible news channel affiliated to global CNN.

The posting by S Wittet has skirted the main issue of violations of Indian ethical rules on clinical trials by the PATH study and has not given even one example of the alleged 'misinformation' by the CNN-IBN team. The following points needed to be noted:

(a) As per Indian laws, it is mandatory to conduct Phase III trials in India on all new drugs and vaccines before marketing approval is given in order to determine if there are any ethnic issues. In the case of HPV vaccine Gardasil, a trial was conducted only on 110 children and it did not include a single subject from the tribal community, a totally distinct indigenous ethnic group. Prima facie, the Drugs Controller General, India (DCGI) did not fully comply with the Indian laws. This matter along with other issues is being investigated by a special committee appointed by the Health Ministry. There is widespread concern about the functioning of the drug control system in India which is perceived to be overly industry-friendly.

(b) There is no provision for the so-called 'post-licensure observational study' in the Drugs and Cosmetics Rules of India. The Health Minister of India in a parliamentary debate on the issue of HPV vaccination has admitted that the study was 'Post-Marketing Trial (Phase IV).'  Such trials have to follow certain well defined procedures and their objectives include the study of safety, efficacy, drug-drug interactions etc. Such studies are extension of Phase III pre-approval trials on a much larger scale.

(c) A Phase IV study is to be undertaken only 'if required by Drugs Controller General, India (DCGI).' No such requirement was ever decided upon much less communicated to the manufacturers of HPV vaccines or PATH.

(d) Much before the HPV vaccine was approved in the middle of 2008, PATH decided on its own in the year 2007 to conduct a self-defined 'post-licensure observational study' on over 25,000 girls in India.

(e) The Indian Council of Medical Research (ICMR) is not a regulator of clinical trials. It has claimed that it was involved only in giving technical advice to PATH as requested.

(f) Under the Indian laws no clinical trial, by whatever name it is called, can be conducted on minors without explicit, written and informed consent from guardians or parents. In the PATH trial, girls staying in hostels (inmates) were enrolled for the trial which is illegal under the laws of the land. In one case the sponsors accepted 'consent' given by a teacher on behalf of 278 minor girls. In another documented case a minor, illiterate girl affixed her thumb impression on the Informed Consent Form on being asked to do so by the organizers. Are these 'informed' consents or just fig leaves?

(g) The literature distributed by PATH on HPV vaccination trial carried the symbol of a rural programme run by the Ministry of Health and Family Welfare that gave an impression to the illiterate tribal people that the project was organized by Indian Government just like other immunizations programmes on polio, DPT etc. This was unethical and illegal. Some parents subsequently complained that they allowed their daughters to be vaccinated under the impression that it was a government campaign.

(h) Under Indian laws when ever a trial is conducted on minors, initially older children are to be enrolled followed by younger children. This rule was violated in the PATH sponsored study.

(i) Many professional associations of doctors in India have nexus with the pharma companies and have financial ties with the drug industry so much so that the regulator, the Medical Council of India, had no alternative but to ban such relationships by a new directive issued in December 2009.

(j) There is widespread concern about foreign drug companies using poor, illiterate Indians as cheap guinea pigs to test new molecules. Even highly credible media in the United States and Europe have taken note of this malpractice. Just one of many examples: BBC's long documentary 'Clinical Trials in India: the Dark Side.'

Dr. Chandra M. Gulhati
Editor, Monthly Index of Medical Specialities (MIMS)
New Delhi 110019. India
e-mail: seeemgee@yahoo.co.uk