Research in the developing world
There is a growing concern about the potentially exploitative nature of research in developing countries, conducted by researchers from the developed world (1). Some of this research would not be possible in developed countries.

Externally funded research in developing countries has been justified on the grounds that it will benefit the health of people in these countries, changing global inequities in health. At present, there is only one physician for every 100,000 people in Burundi compared to 607 in Italy (2). More than 90 per cent of one-year-olds are immunized against measles in Australia, Sweden and the USA compared to 49%, 67% and 77% in Sudan, India and Bangladesh respectively (2) Research can change this, it is argued.

However, what are the real reasons for global inequities in access to education, employment, clean water and health care? There is a need to address the underlying reasons for the ever-widening gap between those who have and those who don't. Just 10% of annual health research expenses address 90% of the global burden of disease, mostly in developing countries (3). This needs correction with more money going for
research on health problems of the developing world. Is this happening through externally funded research?

Some ethical issues
Some argue for different standards of care for research subjects in the developing and the developed world (4) They suggest that in any case there are low standards of care in developing countries, and these countries do not have the resources to provide international standards of care. They also justify lower standards of care with the argument that the research will have indirect benefits for the subjects.

Researchers from the developed world can help improve the health of deprived populations in other ways. The standard of care for research subjects must be the same in the developing and the developed world. Permitting the 'best local care' gives an incentive for research to be conducted in developing countries in order to save costs. Further, interventions found effective should be made available to research subjects after the trial is completed.

In Nigeria, a multinational company tested an antibiotic in the middle of a meningitis epidemic without participants' informed consent (5). One might argue that subjects are protected from exploitation, as research projects will undergo ethical review by local Institutional Review Boards (IRB). However, there are many instances of ethical review boards permitting unethical research. For example, in Kerala, India, an experimental anti-cancer drug was tested illegally but with the approval of the local IRB (6). IRBs must be made accountable. The appointment of IRB members and functioning of IRBs must be transparent, credible and fair.

'Informed consent' is often obtained in an unsatisfactory manner during research in the developing world (7). An independent third party should obtain informed consent, in order to ensure that it is informed and free from coercion. Potential subjects should be given all the relevant information, in a clear manner and in their own language. There is no reason to assume that non-literate research subjects in developing countries are unable to understand the elements of informed consent.

Researchers must inform the IRB of any conflicts of interest. These should also be explained to research subjects who should be aware that they are free to refuse participation in the study. Finally, it should be mandatory to consider conflicts of interest of IRB members who may have a vested interest in the research project.

Research in developing countries should be based on core ethical principles of equality and respect for the rights of research subjects.

References

Karlsson Y. Unethical research in developing countries is supported by western governments Lakartidningen 1997; 94: 3611.
Human Development Reports. Commitment to health: resources, access and services. [serial online] 2004. Available from URL: http://www.undp.org/hdr2004. (Accessed November 24, 2004)
The 10/90 World Health Organization Report on Health Research. [Serial online] 2004. Available from: http://www.globalforumhealth.org. (Accessed November 24, 2004)
Hyder AA, Dawson L. Defining Standard of Care in the developing world: The intersection of international research ethics and health systems analysis. Developing World Bioeth. 2005; 5: 142- 152.
Stephens J. As drug testing spreads, profits and lives hang in balance. Washington Post, December 17, 2000; Page A01
Mudur G. Indian doctors defend "unethical" anticancer drug trial. BMJ 2001; 323: 299
Rothman DJ. Clinical trials in "developing" countries: is there a special "Third World" ethic? Z Arztl Fortbild Qualitatssich. 2003; 97: 695-702

Waris Qidwai, Associate Professor, Family Medicine, Aga Khan University, Stadium Road, PO Box 3500, Karachi 74800 Pakistan. email: waris@akunet.org

Who participates in clinical trials?

It has been more than 70 years since the US Public Health Service started documenting the effects of syphilis on 399 human test subjects -- all of them black, all of them poor and most of them illiterate. None of them were informed that they were infected with syphilis; they were also not told the real purpose behind the experiment (1). The world has been aware of this horrible truth of Tuskegee since 1972. Since then, we have come a long way in terms of monitoring of clinical trials and observing ethical guidelines for experiments on human subjects.

Still, innumerable trials are done, especially by pharmaceutical industries and commercial research organisations that do not follow the ethical norms. Often, participants are not fully informed of the risks involved, while the benefits are over-stated. These are examples of ethical misconduct.

This article does not talk about such trials but rather about committed research institutes and researchers who strive to conduct research following ethical norms. In such trials research protocols are reviewed and approved by ethical review committees. Issues of informed consent, disclosure of risks and benefits to participants, their rights, and so on, are addressed. It is also ensured that benefits for participating in the trial are not an undue enticement for an individual to participate and face unknown risks.

We are a non-governmental, not for profit organisation working on medical and social issues related to HIV/AIDS. As a part of our work we interact with various stakeholders of such trials. We are confronted with ethical issues involving such research as a part of our work. The question that comes to our mind is: “Why should people participate in any research that can expose them to the unwanted effects of the drug or vaccine?” The usual answer we get when we ask this question is: “they participate for the up gradation of science,” indicating that participants’ motives are mostly altruistic. When science is for the betterment of humanity it is the responsibility of all of us to contribute in it. But when we look at the profile of the majority of participants of such trials we see that they are from economically backward strata in society. They are less educated and rarely are professionally related to the topic of the research. Is science is the sole responsibility of these people? Surely not!

We need to examine the motives behind people’s participation in such trials. Are there other advantages in participating? Or do they have a sense of obligation towards the person who motivates them to participate? Do hierarchy and power structures operate in spite of the researchers’ good intentions? Is it enough to take participants’ ‘informed consent’ or do we need to do more?

Why do those involved with such research not participate in these trials? Those who are involved in conceptualising, designing as well as implementing research are in the best position to understand all the risks and benefits of the study, and its importance to build scientific knowledge. During informal discussions with such people they point to ‘conflict of interest’ as a reason for non-participation. Could this issue be addressed differently? If at all there is a conflict of interest, researchers working on the project should refrain from participating, but other colleagues from the institutions or their relatives/ friends can surely participate. This would actually motivate outsiders as well.

This raises many questions: Do participants receive true and complete information regarding the trial’s safety? Are the benefits of participating in the study over-emphasised? Are we taking advantage of people’s emotional and/or financial status to increase participation in the study? Would a detailed understanding about the issue discourage people from participation?

We must take action against blatantly unethical trials. We must also take a second look at research that may be questionable even though it seems to follow ethical guidelines.

Sanjeevani Kulkarni, Shrinivas Darak, Vinay Kulkarni, Prayas, Athawale corner, Sambhaji Bridge corner, Karve Road, Pune 411004. email: prayashealth@vsnl.net

Reference

1. US National Centre for HIV, STD and TB Prevention. The Tuskegee Timeline. Available from URL: http://www.cdc.gov/nchstp/od/tuskegee/time.htm (Accessed April 10, 2005)

Problems with the availability of narcotic medicines

In December 2004, the Maharashtra State Chemists and Druggists Association issued a circular (1) telling their members to keep records of every tablet, injection, capsule and syrup of all psychotropic substances and antidepressants marked as ‘Nrx’. Much has appeared in the press since then on the non-availability of life-saving medicines without prescriptions. Patients questioned pharmacists’ integrity. The Food and Drug Administration (FDA) was held responsible for patient unfriendly rules. We decided to investigate the subject.

The Narcotic Drugs and Psychotropic Substances (NDPS) Act (2) was enacted in 1985 to regulate the manufacture, sale, purchase, stock and use of narcotic or potentially addictive drugs. These drugs, which are listed in a schedule (3), may be dispensed only upon prescription. They are used for chronic conditions such as depression, anxiety, tension, psychosomatic and behavioural disorders, and are used for long durations, usually life-long. Since these drugs can be misused (4), their use must be monitored stringently. The Act specifies that pharmacies selling these drugs must maintain a record of all sales. Failure to produce complete records can lead to a heavy penalty and even imprisonment.

When the Act was first enacted, doctors were expected to write triplicate prescriptions with one copy for their records, the second for the pharmacy and the third for the patient. Patients had to go back to the doctor for refill prescriptions every time. The rules were cumbersome but were followed.

Over the years, this practice fell into disuse. Prescriptions were filled by the pharmacy and handed back to the patients. Eventually many scheduled drugs started getting dispensed without a prescription to friends, known regular patients and on special requests. We can easily imagine how such sales were accounted for and where the profits from such sales went. This holds equally true for private and public sector pharmaceutical companies. If the drugs were sold without bills there was no tax paid. Pharmacists, druggists and the authorities all have tar on their hands.

It is believed that the Narcotic Bureau woke up after a big haul of illegal stock of these medicines. Subsequently, it decided to enforce existing regulations. In December 2004 the Nagpur District Chemists and Druggists Association (NDCDA) informed its members (1, 6) that the Narcotics Bureau was harassing distributors, stockists and retailers and issued instructions to sell Schedule Nrx medicines only to regular customers whom they could identify – it did not mention the need for a proper prescription. This instruction added to the plight of patients suffering from chronic illnesses, who had been getting these essential drugs conveniently from pharmacies. The NCDA’s action was condemned in the press (5). In several instances pharmacists refused to sell narcotic drugs even on a valid prescription.

The enforcement of existing rules is for the good of everyone. But this should have been done slowly so that patients were prepared, and had proper prescriptions in hand. Pharmacists are expected to be aware of the rules but unfortunately even doctors prescribing these drugs are ignorant of the rules.

Instead, the NCDA demanded that narcotic drugs be removed from the purview of the Narcotics Drugs Act and placed under the scope of the Drugs and Cosmetics Act. The authorities gave an assurance that the list of psychotropic substances covered by the Narcotics Act would be reduced. This would mean that fewer Nrx medicines would be monitored, and therefore easily available for abuse. On February 25, 2005 Rule 67 of the NDPS Act was amended and is no longer applicable to those who have a license to sell drugs under the Drugs and Cosmetics Act.

Effectively, pharmacists put chronically ill patients to inconvenience and then appealed for a relaxation of existing rules. This is a crooked way of getting things done. Regulatory authorities are not in the wrong here. And nor should patients be blamed for their ignorance of the rules.

References

1. Maharashtra State Chemists and Druggists Association. Circular number APS/ MSCDA /2716/ 2004. December 16, 2004.

2. Narcotic Drugs and Psychotropic Substances Act, 1985. Government of India.

3. The Schedule, Narcotic Drugs and Psychotropic Substances Act, Section 83.

4. Varghese G. 30% addicted to OTC drugs. Sunday Mid-Day, Mumbai, February13, 2005. p. 13, column 1-3.

5. Shrivastav S. NCDA decision puts patients, pharmacy owners in trouble. Hitavada, Nagpur. January 16, 2005. p 1 and 7.

6. Sakal V. ‘Narcotics, psychotropics aushadhanchi vikri thambavinyacha nirnay mage’ (Marathi). Sakal, Nagpur. February 11, 2005. p 1, column 6-7.

7.All India Organisation of Chemists and Druggists. Circular APS/AIOCD/2178/2005. Dated March 2, 2005

Vijay Thawani, K J Gharpure and Shyam Shukla, Government Medical College, Nagpur, and Sunita Sharma, Indira Gandhi Medical College, Nagpur. Corresponding author: Vijay Thawani, 14-A, Jeevan Jyoti, Clarke Town, Nagpur 440 004. e-mail: thawani_ngp@sancharnet.in