Encouraging Health Research in Developing Countries

by Ian Magrath

The benign cycle of research-induced socioeconomic benefits—health research improves health, which accelerates economic development, which permits better financing and infrastructural support, thus having an ever-increasing effect. Input to start the cycle is required in the form of external aid. This need should decrease over time. Figure 1

A "New" Approach: Evidence-based Medicine

Having spent the best part of my career in medical research, I was puzzled some years ago by a new term—evidence-based medicine—that was suddenly on everyone's lips. I had always assumed that the use of evidence to guide clinical interventions is a fundamental principle of medical practice. The term seems to have "gone public" in November 1992, when the Journal of the American Medical Association (JAMA) published an article titled "Evidence-based Medicine: A New Approach to Teaching the Practice of Medicine." In the nine years that have since passed, PubMed lists over 7,400 publications in which the term is used. Somehow, the sudden preoccupation with evidence just a few years before the close of a century in which so many scientifically and technologically-based advances in health care had occurred suggested a rather belated recognition of a paradigm shift in the practice of medicine—probably by those more concerned with education and service delivery than by medical scientists. The latter, after all, had been responsible for the unprecedented progress made, and presumably had long been convinced of the value of evidence, as well as its variability in quality. Still, I remain surprised that this debate took so long to emerge.

A Century of Progress

Teach thy tongue to say I know not and thou wilt progress. —Moses Maimonides

An idea of just how far medicine has come in the last 100 years may be gained by perusing Osler's famous textbook of Medicine, written at the turn of the 20th century. Despite the myriad of salves, potions, tonics and herbal remedies which had abounded since the days of the ancient civilizations of Egypt, China, India, and later, Greece, little beyond palliatives and placebos was available for most medical conditions. As pointed out by Osler himself, essentially the entire pharmaceutical armamentarium could be carried in the physician's bag. Pharmacy had progressed little since the days of the great Arab physicians, pharmacists and alchemists of the Córdoban caliphate, which finally yielded to the Spaniards in 1492—the same year that Columbus discovered America. In Osler's day, there were no antibiotics, no effective anti-cancer agents, and surgery—still remarkably primitive by today's standards—was the only available therapy for cancer. Although Roentgen had discovered X rays in 1895, and only two years were to pass before their astounding effect on cancer was to be observed, it took many years for radiotherapy to become a standard component of the therapeutic repertoire. Still, a dramatic acceleration of the march of progress was about to begin, based on a painfully accumulated foundation of knowledge that extended back to the mists of prehistory. Whether ancient peoples realized it nor not, much that they did, whether relating to agriculture, navigation, the development of tools or the practice of medicine was based on scientific observation, frequently blended inextricably with magical and religious practices, and clouded by a liberal helping of misconceptions. Evidence-based medicine then is in fact nothing new, for the evidence referred to is empirical—i.e. the clinical test of the likelihood of a history or physical sign being something indicative of a specific diagnosis, or whether an intervention works or not, regardless of whether the mechanism is understood. The Egyptian medical papyri, for example, are clearly based, at least in part, on empirical observation. Unfortunately, an evidential basis for clinical practices, however ancient the concept, is often difficult to discern, and even now, individual physicians have considerable license in recommending treatment. The monitoring of clinical practices and outcomes remains limited (except in the context of clinical research), even if the concept of evidence-based medicine has led to the creation of more practice guidelines and more reference to the results of clinical trials.

Surgical Strategems

Surgery for example, is a discipline which has evolved dramatically in the course of the last 100 years (thanks to the use of anesthetics, aseptic techniques, blood transfusions and antibiotics), but more, perhaps, through the efforts of surgical virtuosos than through team efforts and carefully conducted clinical trials. Originally limited to the lancing of abscesses and the management of wounds, with amputation being among the more ambitious of procedures, it moved rapidly in the early years of the last century to the introduction of routine abdominal and thoracic surgery, through the conduct of ever more extensive resections, particularly for cancer and, finally, to its present phase in which restoration and replacement procedures (whether by transplantation or prosthesis) represent the pinnacle of the surgeon's achievements. In part because of the awe inspired by technical feats of this kind, coupled to the powerful influence of tradition, we are still only just moving beyond the grossly mutilating procedures (ranging up to hemicorpectomy—removal of the lower half of the body) that were used to control local spread of cancer. Like radiotherapy, they were all that could be offered to the cancer patient, and it has taken decades to recognize that many have been rather over-enthusiastically applied, or remained standard practice long after evidence of less mutilating but just as efficient alternatives had been obtained. Halstead, for example, described radical mastectomy (en bloc resection of the breast, pectoral muscles and axillary nodes) in 1894, and this remained unchallenged as the surgical approach to breast cancer for 70 years. Eventually, after a phase of even more extensive surgery (extended radical mastectomy) but also, many randomized trials conducted in the 1970s and 80s, the operation was replaced by total mastectomy and axillary dissection. It was not until 1990 that the National Cancer Institute was able to develop a consensus view in which it was accepted that breast-conserving surgery and radiotherapy is as effective, in stage I and II patients, as removal of the breast and axillary lymph nodes. Such patients would, in an earlier era, have been subjected to radical mastectomy.

Old habits clearly die hard, and innovators often receive short shrift (Semmelweise, for example, was driven out of Vienna in 1850 for his novel views on hand washing between performing autopsies and examining patients!). Perhaps we should not be surprised, then, that in the presence of a conservative profession, benefits to the patient and public and new educational approaches may lag far behind the march of science.

A Parallel Debate

Health research is the ultimate international public good. —Gro Harlem Bruntland

Delayed though the debate on the basis for medical decision-making may seem to have been in a century in which medical science made such huge strides, a similar and equally surprising debate on the role of research in improving health in developing countries was simultaneously taking place. In 1999, Dr Gro Harlem Bruntland, Director-General of the World Health Organization (WHO), pointed out in a keynote address to the Global Health Forum that it was only in 1990 that the World Health Assembly had "emphasized the need to develop health research and the necessary knowledge on which national health policies should be based." One might have expected, as in the case of evidence-based medicine, that such a conclusion would have been made sooner, being a natural corollary of the paradigm shift that had occurred in medicine decades before. In that same year, in her words, "the concept of Essential National Health Research took root ...and on that basis, the Council on Health Research for Development (COHRED) has developed collaboration with developing countries and gathered useful experience." Reviewing the remarkably brief history of the concept among policy makers that research is an essential element to improving health, and that the health of a population has a significant impact on its economic development, Dr Bruntland mentioned that in the World Bank's World Development Report of 1993, which was focused on health, the central importance of research was underscored. In 1996, she continued, the WHO Ad Hoc Committee on Health Research Priorities published a report on the need and criteria for investing in health research and development, while in the same year, the Global Forum for Health Research was established. In 1999 the WHO Report "demonstrated that a large proportion of the health achievements of the 20th century can be attributed to advances in scientific knowledge as they were translated into more effective technologies and health-promoting behaviours." Such a conclusion would surely seem to be self-evident to medical researchers. Nonetheless, given the new cloak of respectability for research, in January 2000 the World Health Organization announced the creation of a Commission on Macroeconomics and Health to clarify the link between health and poverty reduction and to study how concrete health interventions, based on scientific research, can lead to economic growth and reduce poverty in developing countries.

It is remarkable that only in the report of this commission, dated December 2001, was it recognized that not only does poverty cause ill health, but that ill-health contributes to poverty. The Commission drew attention to the huge global inequities that exist and provided specific recommendations for "Investing in Health for Economic Development." A key recommendation was improvement of access of the world's poor to essential health services through partnership with high-income countries (see figure 1). This is, in the context of cancer, a major objective of the INCTR.

Health Research For Economic Growth

All countries, no matter how rich, will suffer at an economic level when a fraction of the population not only consumes resources during periods of ill-health, but fails, while ill, to contribute to the economy. In the case of sickness in mothers, negative family consequences often result, whilst a child's education may suffer greatly as a consequence of repeated illness or chronic ill health. Yet in an era in which research into agriculture, manufacturing, transportation, energy and defense have been considered of vital importance to economic progress, national health research has, in comparison, been neglected. Governments of industrial countries as well as developing countries have assumed that adequate health of the population can be assured on the basis of existing knowledge (or has a minor economic impact), and, ergo, the conduct of country-specific health research is a luxury. Much of the focus of the last several decades has, therefore, been on the administration of health systems. Governments, particularly of affluent nations, have made major contributions to the expansion of medical knowledge, albeit with the emphasis on basic research. Such emphasis is not necessarily inappropriate since, for example, an understanding of the cellular and molecular changes associated with cancer will eventually lead to more rational treatment, and also make it possible to prevent disease through non-behavioral interventions. However, the relative paucity of clinical research, and the tendency to consider empirical observations as "not real science" has had a deleterious effect, particularly when one recognizes that the bulk of the advances in interventions in cancer have been based on empirical observations (chemical compounds, for example, have been screened for anti-cancer activity, and only now are we entering an era in which drug design is possible).

The lag phase between knowledge acquisition and translation into benefits for people may have contributed to the uncomfortably high proportion of the educated public throughout the world that looks upon biomedical research as serving only to enhance the careers of biomedical scientists through publication of their results in scientific journals. Politicians have often regarded research as a drain on scarce resources that could be used directly for health interventions rather than a means of ensuring the most efficient use of existing resources, and as such, an essential tool in the evolution of a rational and effective national health policy. Even the scientifically trained have often espoused the same opinion, at least in the context of health research in developing countries. Thus, the recognition that health research is likely to enhance macroeconomic development, even in the poorest countries, is a welcome development, since instead of being considered an unaffordable luxury, developing countries will hopefully recognize that they cannot afford not to conduct research relevant to their own national health problems. In policy parlance, health research has finally been recognized as being of "strategic importance."

Opportunities Missed

While recent emphasis has been on essential national health research, it is worth pointing out that science knows no boundaries, and that knowledge, wherever created, will likely be of broad benefit. Indeed, one might hope that the term "strategic" will eventually take on a global connotation, rather than implying narrow national interests. Meanwhile, according to the Global Forum for Health Research, 90% of health research is directed toward 10% of the global disease burden. Clearly, the world is missing a huge opportunity to increase the sum total of biomedical knowledge and to use this information to more effectively solve health problems. To rectify this, major investment in the capacity of developing countries to conduct research must be made. They represent the bulk of the planet's human resources, and provide unique opportunities to conduct epidemiological, genetic and therapeutic research in a wide range of health problems, including cancer. They also provide numerous opportunities to examine new approaches to the financing and delivery of health care, and health-related behavioral modification. For these reasons, the twin benefits of health research—improving the lot of individual patients while speeding up the process of socioeconomic development—surely constitute a universal good. It will be for each government to decide the degree to which it will support the creation of basic knowledge, which may have no immediate relationship to a clinical problem even though it should eventually translate into human benefits, and how much will be spent on acquiring more empirical information in the form of clinical studies— i.e. expanding the foundation of evidence on which clinical decisions are made. Both are important, but the poorer countries may be less able to invest in basic research as opposed to extending their foundation of evidence on which to base health policy and specific interventions. Government spending, of course, will be supplemented by the efforts of private organizations, which may significantly alter the overall pattern of ongoing research. Nonetheless, the recognition that solutions cannot simply be "taken off the shelf" but must be tailor-made for the problems of particular developing countries represents a critical step forward.

Research - the Way Forward

The recognition of the role of research in improving health care in developing countries and the clear commitment of the WHO to research are important steps forward which should help to ensure that available resources—present and future—are put to the most efficient use. There is much to be done, but the ambience has been created at the beginning of the new century that should make it easier to accelerate the rate of progress in improving health and combating poverty through the conduct of relevant health research followed by application of the lessons learned. As progress is made, and epidemiological transitions continue, cancer will have an ever increasing importance as a cause of premature mortality. There will be much for the INCTR to do.