|
Sci Tech
SPEAKING OF SCIENCE
Clinical trials: no man is more equal than another
|
For the FDA, ethical considerations are expendable when research subjects live half a world away
|
— Photo: R. Ragu
Not binding: Though not legally binding, the Helsinki Declaration is by and large being followed by all.
What is the purpose of a human clinical trial? In order to ensure that the drug or the treatment is safe, effective in appropriate doses and does not cause ill effects. Practice of human trials has been on for decades, even centuries. In early days, the chemist or physician used himself as the guinea pig.
Widely effective
But statistics is important to ensure that the treatment is widely effective; this demands that a sufficiently large number of people be used for the trial, and also an equal number of ‘control’ group be used to whom either sham or no treatment is given.
It is the need for large number of ‘volunteers’ or ‘subjects’ that is the contentious issue. In the 1920s and 30s, some doctors and companies in Europe and the U.S. used vulnerable groups such as jews, gypsies and tribes in Germany and Russia, and prisoners and blacks in the U.S. for such trials.
Nuremberg code
When these practices came to light, particularly after World War II, many nations got together and came out with the Nuremberg Code, with ten principles, which was then made into the Declaration of Geneva in 1948. This declaration laid down the principles of clinical ethics.
The World Medical Association (WMA), a group of medical practitioners and researchers from many countries (largely from Europe and North America, with but a sprinkling of other nations) convened a meeting in 1964 in Helsinki, Finland, expanded on the two earlier guidelines and came out with the Declaration of Helsinki.
This declaration is a set of ethical do’s and don’ts for medical doctors and researchers regarding human experimentation.
Though not legally binding, this is by and large being followed by most doctors, researchers and companies throughout much of the world.
The declaration wants that the subject on whom the trial is done should be fully informed of all the positive and negative aspects of the trial, and give consent to be a participant. It also allows for proxy consent, such as from a legal guardian, or a community leader.
Review board
As expected, revisions have been to the articles of the Declaration made from time to time.
The first revision in 1974 required that an independent ethical committee or institutional review board be established, which would permit, modify or deny the conduct of a trial.
Two subsequent revisions (1983, 1989) included seeking the consent of minors, and more details on the functions of the ethics committees.
Even as the Helsinki Declaration was accepted and followed, two other independent guidelines were developed, one by the Council for International Organizations of Medical Sciences (CIOMS) and the other by the World Health Organization (WHO).
It is at this juncture that some differences began cropping up and, some say, vested interests played a part in setting up such parallel set of guidelines. For the moment, all three guidelines were pretty much the same, but for minor differences. The pot got stirred in 1994 with the trial that an American company wanted to do.
Departure point
The trial of an anti-HIV drug they wanted to conduct, not in the U.S., but in a developing country, turned out to be a point of departure.
While some subjects were to be given the drug, the ‘control’ group was to be given a placebo (an inert substitute). Now, while patients in the U.S. had unrestricted access to the drug, those in the developing country had not. Interestingly, both the U.S. agencies and WHO actually said: “Placebo-controlled trials offer the best option for assessing a drug regimen”.
Ethical standards
This ran in contrast to the CIOMS guideline that said: “The ethical standards applied should be no less exacting than they would in the case of research in (the sponsoring) country”.
The Declaration of Helsinki quickly came out with Revision 4 in 1996, stating: “Human subjects in any part of the world should be protected by an irreducible set of ethical standards.”
The split between Helsinki and U.S./Europe became noticeable. Learned journals in medicine were hot with debate, and words like ‘ethical imperialism’, ‘pluralism’ and ‘ethical universalism’ came into the discussion.
Take the case of the trial, in 2001, of a drug that acts against sudden lung collapse in children and thus saves lives. Initiated by the U.S. firm Discovery Labs, this wanted to try the drug on children in a Latin American country.
Rather than compare their drug with one of the several effective drugs already in use, the company wanted to give inactive placebos to 325 children in the control group.
The Food and Drug Administration (FDA) of the U.S., which clears such trials, warned them that this was unethical, since effective treatments were available in the U.S. and Europe (even if not in the Latin American country).
The company then had to change the protocol and gave the control group the alternative active treatment. This was in keeping with the Declaration of Helsinki.
Yet, with increasing pressures from companies and sponsors, FDA is starting to buckle.
It has announced that starting October 2008, it will shelve the Helsinki Declaration, and adopt a new standard called Good Clinical Practice (GCP).
This is a document prepared by drug regulators and drug companies from the US, European Union and Japan.
As the journal Nature notes in its 22 May 2008 issue: ‘Although GCP deals with subject protection, it is in essence a manual on how to conduct rigorous clinical trials, not a human rights document….If FDA jettisons Helsinki, it risks sending a message that ethical considerations are expendable when research subjects live half a world away’.
Indian agencies such as the Drug Controller General of India, Indian Council of Medical Research (ICMR), and contract research organizations that conduct and oversee human trials, and also the institutional ethics committees should take note.
Overall, the Helsinki Declaration argues for ethical universalism.Let us not follow FDA and change our guidelines. After all, it cannot be that some humans are more equal than others.
D. BALASUBRAMANIAN
dbala@lvpei.org
Printer friendly
page
Send this article to Friends by
E-Mail
Sci Tech
|
