Fw: Clinical trials: some ethical issues

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From: " Kathi " <pureheart@...>

Sent: Sunday, October 13, 2002 9:38 AM

Subject: Clinical trials: some ethical issues

> MJ

>

> Clinical trials: some ethical issues

> Research often promotes commercial interests while exploiting vulnerable

> participants

> Sandhya Srinivasan

>

> All research designs have their strengths and limitations. A comparison

> of lung cancer in the US and India with average tobacco intake in the

> two countries could say something about

> whether cigarette smoke causes cancer. So could following two groups, of

> smokers and of non-smokers, over ten years, to see how many get sick,

> and how many die, and of what. A

> look at a death register, tallying causes of death to the dead people's

> occupations could yield information on occupational risks. Comparing

> school children's exam score with their

> blood lead levels indicate the effect of lead. Giving one group of AIDS

> patients AZT and the other a sugar pill, and then measuring the blood

> levels of the virus in the two groups will give

> information on whether the drug works.

>

> The 'gold standard'

> Clinical trials to introduce a new drug or other therapy, are based on

> the concept of the randomised, placebo-controlled clinical trial,

> sometimes called the 'gold standard' of research

> studies (1). A study sample representative of the population is divided,

> at random, into two groups, equal in every way. One (the experimental

> group) is given one drug and the other (the

> control group) either a placebo (a sugar pill) or perhaps another, older

> treatment. Researchers then measure for some predefined outcome, such as

> getting better faster, or evidence of

> a lower viral load. If people taking the drug get better faster than

> those taking the sugar pill the drug works. Ideally, neither participant

> nor researcher should know which group a

> participant belongs to. All this is in order to reduce various biases on

> the final outcome. The clinical trial is thus considered to be a

> potentially powerful research tool, and a source of

> very accurate knowledge. It is also a rich source of discussion on

> ethics.

>

> Informed consent.

> Informed consent is a concept central to research. All the various

> scandals about clinical trials currently in the news involved the

> questions : did the participants know they were part of

> a trial? Did they give their informed consent to participate after being

> told of the possible risks, and the limited benefits? Too often, they

> did not.

>

> Informed consent was not received from the 1,000 Indian women with

> early, pre-cancerous changes in the cervix, were recruited by an

> ICMR-approved research group and 'monitored' to

> record the progression to cervical cancer (2). It seems that the women

> were unaware of their health status, and the consequences of

> participating in such a trial. The notion of informed

> consent was incorporated into ICMR protocols much later.

>

> Was informed consent obtained from the over-50,000 women in India and

> south-east Asia who were sterilised with the mutagenic anti-malarial

> drug quinacrine, administered with an IUD

> inserter, to cause inflammation and blockage of their fallopian tubes?

> Not likely, going by the comments of the doctor campaigning for such

> mass sterilisations of poor women. While

> noting the WHO's opposition to this technique in the absence of certain

> toxicological tests, this doctor suggests that his colleagures obtain

> signed informed consent - but only from

> women in developed countries, because they might just decide to sue.

>

> " Faced with the dilemma that the quinacrine pellet is the method of

> choice for some women even though quinacrine is not approved by

> governments or international bodies for this use,

> an increasing number of physicians in some countries have decided to

> offer it to some of their patients... Women should, of course, he

> informed of these risks and benefits. In

> industrialised countries where malpractice litigation is prevalent, it

> is recommended that written informed consent be signed by the patient " .

> (3) (emphasis added)

>

> Informed but not voluntary

> Are potential participants always capable of giving informed consent ?

> Clinical trials of drugs given to HIV-positive pregnant mothers, in

> Africa and Asia, to prevent maternal-foetal

> transmission of the virus, were attacked (4) because they were testing

> an experimental drug (lower doses of a standard treatment now being

> given to women in the West) without

> providing the control group the standard treatment - something that

> would not be permitted in developed countries. One of the investigators'

> arguments was that the women concerned

> had given their informed consent.

>

> What kind of informed consent can be obtained in such circumstances? A

> woman knows she could pass on a fatal virus to her child, and is given

> the opportunity to participate in a trial

> which just may give her access to a possibly effective drug, a drug she

> cannot afford on her own. (this is a virus acquired because of her own

> vulnerability.) How voluntary can her

> consent be ?

>

> With the benefits of science

> For some time, pharmaceutical companies wanting to market new drugs have

> been required to do extensive clinical trials showing them to be both

> safe and efficacious on human

> beings, though there is plenty of scope for debate on these

> requirements.

>

> If drugs undergo some measure of rigorous testing, new diagnostic

> methods and techniques have been introduced without such cautions. And

> procedures are being done in the name of

> trials, or justified by earlier 'trials', independent of regulation by

> any ethics committee.

>

> Quinacrine sterilisation is being done in parts of India on the basis of

> unofficial trials: more than 50,000 women have been sterilised in this

> manner) despite the WHO's refusal to

> endorse it, and despite public interest litigation in the Supreme Court

> against the practice.

>

> In fact, a 'demonstration video' of the procedure was screened at a

> recent " international conference on fallopian tubes " , where doctors

> actually called for compulsory sterilisation of

> women after two children. And even as private doctors practice their own

> 'population control' campaigns, the Karnataka state government will

> reportedly include the procedure in its

> 'cafeteria' of contraceptive choices.

>

> Incomplete information

> Many new techniques are being promoted for use without the backing of

> clinical trials. Some techniques - tested or untested - mean money to

> the instrument manufacturer. Other

> techniques, involving profit to surgeon and manufacturer, may have

> specific, limited use, but are being promoted to the medical profession

> and the public as the latest, superceding

> earlier methods. For example, endoscopy is promoted through 'workshops'

> where doctors learn the technique, to the public through public

> relations companies, without discussion the

> risks and benefits compared to open surgery.

>

> Evidence suggesting that endoscopic surgery is in many situations of no

> greater benefit than open surgery is not publicised.

>

> Paying to be experimented on?

> Another form of deception, profitable to doctor and instrumentation

> industry, at the cost of the patient, is the practice of using an

> experimental technique to gather information on safety

> and efficacy. Recently, the US FDA started requiring that manufacturers

> of new surgical devices prove their safety and efficacy in clinical

> trials before selling them commercially.

>

> Manufacturers must then be forced to make their profits in developing

> countries, where scarce resources for health care are squandered on

> expensive techniques of doubtful efficacy.

>

> It was recently pointed out that American patients would have access to

> a particular experimental procedure only through a randomised clinical

> trial in which they would hope to be

> assigned the treatment arm.

>

> In India, however, patients with no other option of treatment are being

> offered this experimental procedure. Hospitals offering this procedure,

> which has been publicised through the

> press, don't have to spend a ruppee. The company maintains the machine

> free of charge, charging only for the special catheters - for which the

> patient pays. When a given number of

> catheters is used, the machine becomes the hospital's property. In other

> words, patients in India are paying for an experimental procedure -

> though they are not likely to know it.

>

> How will the results of the Indian operations be used? Will Indian

> people be providing data - of uncertain value - to the company, in

> support of the procedure?

>

> Suggestions have been made to ensure that research is conducted under

> committees that back both scientifically valid and ethical research (5).

>

> Some examples follow:

>

> Have the researchers gone through the literature and ensured they're not

> repeating old studies? Are the results of research being made publicly

> available?

>

> The authors note the tendency to publicise research showing positive

> results and downplay those showing that a particular treatment does not

> make much of a difference, or even does

> some harm.

>

> They point out: " When research is conducted in this manner, the losers

> are patients who must: accept the harmful side effects of ineffective

> forms of care; accept advice about the

> effects of health care which is based on evidence that is less complete

> than it should be; participate in research which has been conceptualised

> and designed on the basis of

> unnecessary incomplete information; and contribute to research (both as

> indirect funders and as patients) which may not be published if the

> results come as a disappointment or as an

> embarrassment to the investigators or sponsors " .

>

> In the final analysis, the people concerned are those who pay for such

> research, whether through government-funded trials, by participating in

> them, or by paying for the treatments

> which follow.

>

>

>

> References

> (1) Freedman B et al: Placebo orthodoxy in clinical research II:

> ethical, legal, and regulatory myths. Monash bioethics review. 1998 17

> (1): 'Ethics Committees: a special supplement'

> 10-20.

>

> (2) Mudur Ganapati: Indian study of women with cervical lesions called

> unethical. British Medical Journal 1998; 314 (7087).

>

> (3) Kessel e et al: Quinacrine pellet method of non-surgical female

> sterilisation. Proceedings of the VIIIth world conference on human

> reproduction, joint IVth world congress on

> fallopian tube in health and disease, Bali, Indonesia, April 1993.

>

> (4) Angell M: The ethics of clinical research in the Third World. New

> England Journal of Medicine. 1997; 337: 847-849.

>

> (5) Savulescu J et al: Are research committees behaving unethically?

> Some suggestions for improving performance and accountability. Monash

> bioethics review. 1997 16 (4). 'Ethics

> committees: A special supplement'. 4-11.

>

>

>

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