Walk a mile in the moccasins of people with haemophilia.

This issue of Haemophilia contains an article entitled Staunch Protections: The Ethics of Haemophilia Gene Transfer Research by Jonathan Kimmelman. In this paper, Dr Jonathan Kimmelman, PhD, raises some appropriate ethical issues such as the need to demonstrate clearly and publish a beneficial effect in animal models prior to performing clinical trials, and the importance of obtaining consent that is truly informed. However, we disagree with his belief that it is ethically inappropriate to include people from economically disadvantaged counties in clinical trials, and believe that patients from throughout the world should have access to clinical trials. Current therapy of severe haemophilia involves intensive factor replacement therapy for preventing bleeding-related damage to joints and other organs. While this is very effective, there are several difficulties with such an approach, such as venous access in small children, inhibitor formation, cost, the impact on the quality of life and the overall psychological burden of living with an incurable disease. Gene therapy refers to a treatment in which a gene that encodes a therapeutic protein is transferred into the cells of a patient. This results in the continuous production of the protein, and could translate into a permanent cure for people with haemophilia. Indeed, gene therapy has had a substantial therapeutic effect in dogs with haemophilia that has been maintained for almost 10 years without adverse effects. This is a truly remarkable achievement, and if translated into clinical practice, could dramatically improve the lives of people with haemophilia throughout the world. A major tenet of the article by Dr Kimmelman is that it is ethically wrong to include subjects from economically disadvantaged countries in clinical trials. He states that hemophilia gene transfer trials present a particular ethical challenge because they involve subjects whose medical condition is stabilized by standard therapies . This statement ignores the fact that treatment for approximately 75% of the people with haemophilia in the world who live in economically disadvantaged countries is inadequate. In addition, many people with haemophilia in developed countries are not able to get optimal treatment for various reasons [1]. Here, we present data on the survival and morbidity of the people with haemophilia in India as an example for how existing treatments do not stabilize the condition of patients in economically developing countries. India has a factor VIII usage rate of 0.01 international units (IU) per capita, while the USA has a factor VIII usage of 3.4 IU per capita [2]. Thus, the USA uses 340-fold as much factor VIII per person as does in India. A critical question is whether or not this reduced factor usage results in increased mortality and morbidity in the people with haemophilia in India. Among the 6980 persons with haemophilia who were in the national registry in India in 2004, 44% were under 15 years of age, 35% were between 15 and 30 years, 16% were between 30 and 50 years and only 5% were above 50 years of age. In contrast, counties with a gross national product that is greater than $10 000 such as the USA have 370% as many people with haemophilia who are older than 19 years as people who are younger than 13 years [3]. Thus, on the basis of these data, the USA has many more older people than younger people with haemophilia than are found in India, which strongly suggests that people with haemophilia have a reduced survival in India. Although it is possible that this discrepancy might reflect an overall difference in longevity, the average lifespan for males of 66 years in India is Correspondence: Katherine P. Ponder, Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA. Tel.: +1 314 362 5188; fax: +1 314 362 8813; e-mail: [email protected]