Integral and balanced

Rodolfo J. Stüsser, MD

Clinical Epidemiology & Biostatistics Division, Centro de Investigaciones Clínicas

(Clinical Research Center), Calle 34 # 4501 / 45-47, Playa, Havana-13, Cuba.

[E-mail: [email protected]; Tel.: (537) 23-0087; Fax: (537) 23-0497]

The aim of this paper is to suggest a comprehensive methodology to conceive, teach and make medical scientific research more creative and fruitful, at lower costs, strengthening its internal logic of progress. In the last 50 years, medical research has suffered a crisis of efficiency in its effort to achieve the humane goals of medicine. It has faced the multiplication of its costs, as well as of the costs of medical care, disfavoring the clinical ortho-investigation. Clinical progress is being practically achieved through clinical meta-investigation induced from outside the clinics more by the technological sophistication process, and less by disease and death indexes decrease. The paper mainly exhorts to link the concepts of research and intervention (R&I) with research and development (R&D) of all medical research objects and sites; as well as the empirical and quantitative methods of research along with the rational and qualitative ones. It also conceives medical research in the clinic, health system and basic and technological laboratory as related fields and moments of a unique creative process to solve scientific problems. In this way, medical scientific research would become a more integral and balanced enterprise. This rapprochement across the methodologies shall allow establishing later scientific methodological principles of medicine. Linking explicitly, the ignored theoretical, and interpretative methods along with the empirical and high-technological procedures, is a suggestion. Thus, besides a more complete use of the hypothetical-deductive method, including human experimentation by computer simulation, it argues the utilization of an axiomatic-like method as well. Another proposal is that clinical judgment has to flourish again as a general scientific method not only for particulars, but also for generals formulating new scientific hypotheses to be verified further by clinical studies, as well as by laboratory and sanitary investigations, which would provide a powerful tool to attract more and train better young physicians in clinical research. Finally, it recommends along with very rigorous and integral training programs for clinical investigators, such as the ones of public health and laboratory, the design of theoretical and public health international projects, integrating them hierarchically with the human genome, brain and other basic projects, through a clinical medical one.

Medical scientific research policy and strategy are being subjected to acute debates in the ethical, ontological, and epistemological fields throughout the world, trying to balance ambitious goals with limited means. These discussions are taking place among physicians, investigators, policy makers, industrial managers, philosophers, theologians, and sick and healthy persons, trying to decide mainly upon its logic of progress [1,2]. One polemic is about which research is more human-oriented, if high technology research to cure disease and delay death or low or non-technological research to care and palliate patients, to promote healthy persons and prevent them from becoming sick [3,4]. Another controversy is about which is more effective on a medium and long term for human beings, if complex and expensive research to explain disease mechanisms and cure a little, or simpler and cheaper research to improve the behavior of persons and increase the preservation of health [5,6].

Since the second half of the 18^th-century, the most chronic methodological discussion in medical research continues. It is about the measuring of the partial research facts and their certainty, on the one hand, and the clinical understanding and judgment of the integral research of man as a whole on the other [7,8]. Physiologists and microbiologists solved this challenge integrating observational and experimental methods until early in the 20^th-century. Clinicians and surgeons, specially the generalists, after the amazing advances in statistical designs, high technology, computing systems, and molecular biology that took place fifty years ago, have intensified those debates along with sanitary colleagues of sociological background [9-11]. Nevertheless, the growing confusion of science with technology rose [12], has originated the acknowledgment of the clinical trials of industrial products as the only real scientific kind of clinical investigations. However, independently of the still incomplete use of the hypothetical method, the debate has not transcended enough the empirical methods yet, to include the important theoretical ones [13,14], diluting the attention from its internal logic of progress.

The hypothesis here has four components: 1) Concepts about medical research and intervention (R&I) as well as research and development (R&D), on the person and family, at the home, clinical office or ward, on the community, population, health system and service, at the health zone or center, on the medical model and technology, at the basic or industrial laboratory, are related fields and moments of a unique creative process to solve scientific problems, which must integrates multilaterally their methodologies to achieve more efficacy than when they are used separately. 2) There has to be a rapprochement across those partial medical research methodologies, which also must include the empirical and quantitative methods of research linked with the rational and qualitative ones. It also must include human experimentation by computer simulation, hypothesis’ formulation, law-like generalization, and theory formation that will make medical scientific research enterprise more integral, and shall allow to establish some scientific methodological principles of medicine later [13]. 3) Tacit ontological and epistemological principles of medical science, must be explicited into the conceptual framework of sub-disciplinary, interdisciplinary and super-disciplinary paradigms governing medical scientific research, and must be taught too, to create the critical thought in the clinical scientist. Learning concepts, hypotheses, laws, and theories, in the practical way, but in an abstract way too, will help the practical and empirical clinical investigators in their investigations. 4) The integration and strengthening of medical research's own internal logic of progress, mainly depend on the re-flourishing of clinical judgment as a renewed creative method too. This should provide quite a powerful tool to attract many younger generalist, and specialist physicians giving them a much better training in clinical research.

The aim of this paper is to propose a coherent and comprehensive methodology to conceive, educate, and make medical scientific research, more creative and fruitful with lower expenditures, strengthening its internal logic of progress. The main ethical, ontological, and epistemological challenges of the future goals and means of medical research constituted its framework. The endeavors are addressed to an essential theoretical problem of medical science’s spectrum of problems, and the problem is focused from the broadest angle of 360⁰, instead of the current smaller angles of scope of the empirical problems. This trans-methodological model of medical research is to be applied throughout the ample scope of places, where medical research is being made to enrich the creativity of its isolated methodologies in use, never to supplant them. In addition, it is very far from undervaluing the current methodologies and ignoring the pluralistic and relativistic nature of knowledge. It attempts to seek to shorten the time required for the encounter of the outcomes of the different medical methodologies (the opportune moment to gain the scientific advance)[5], thus accelerating medical scientific progress.

Medical scientific research is passing through a worldwide progressive crisis, especially in the last two decades. Its effectiveness has been diminished to achieve the humanistic goals of medicine. The impact of its outcomes on the health of persons, families, and societies has remained stationary. The health research costs along with the expenditures of health care have been multiplied [2,3]. The clinical ortho-investigation of high quality, guided by internal forces, originated-in-the-patient and investigator-driven, has passed to a second plane for the physician generalist as well as for the specialist [15].

Since the 50ies, the development by biological procedures of basic knowledge about medical models, along with the advancement of new means for health care through the technological development of pharmaceutical and medical-devices, both in the research laboratories, has become the leading external force of medical progress logic. In addition, the improvement of better public health's indexes of deaths and diseases, has been another prominent although less powerful external force of progress [1-4]. The clinical meta-investigation evaluating the technological outcomes of the research laboratory, guided frequently by the present health indexes, is considered the most rigorous clinical research, because it is an extension of the laboratory research in correspondence with public health. Nevertheless, without clinical ortho-investigation the necessary skills to continue doing good clinical meta-investigation are lost [15], and more important, the solutions of the more psychosocial health problems of the person and his family as whole object of research are delayed, because the technology-oriented and index-driven researches are up-today blind for them.

A study between 1953 and 1965 of 7 000 medical research abstracts, presented annually in a US national medical meeting, indicated by their aims, materials and methods, a new trend in its direction: Less research toward clinical patient-centered from 40% to 16% and more toward nonhuman-nondisease or basic phenomena from 6% to 26% [16]. A study of 612 articles in three journals (NEJM, Lancet, JAMA) from 1946 to 1976, revealed an increase of weak research designs (maintaining one third with ten subjects or less) and of clinical trials from 13% to 21% --randomized from 0% to 5% [17]. Lastly, other 444 articles between 1971 and 1991 of those same journals, exhibited an increase in clinical trials from 17% to 35% --randomized from 31% to 76%--, multi-center studies from 10% to 39%, and health service research from 0% to 12% [18].

In the last two centuries, medical research has been progressively diverging mainly in two fields: Clinical research --including epidemiological research-- and non-clinical or basic research [8]. Recently, epidemiological and health researches a broader third field [19,20], not so widely accepted, is attempting to include medical research. In 1995, The John Curtin School of Medical Research, international center of excellence within the Institute of Advanced Studies of Australia, said that "it is focused on basic aspects of biomedical science," and "it must be able to demonstrate the clinical relevance of its fundamental innovations," coordinating with different clinical study units nationally and abroad [21]. Only for the latter, they plan to construct a Center for Clinical Studies. Therefore, the dominant training of medical researchers is to date on basic research in laboratories.

The scope of clinical research methodology has become centered gradually on better-designed and analyzed randomized trials, and on retrospective meta-analysis of their results. In the 90's its interest has become aimed at doing prospective meta-analysis of groups of major multiple centers and countries' clinical trials with tens of thousands of patients [22]. The latter is to achieve enough power to prove faster statistical significant differences in responses to new drugs derived from the research laboratories of industry. Meanwhile, the laboratories have generated methods for accelerating drug discovery, as parallel-compound synthesis [23]. The Cochrane Collaboration for systematic reviews of clinical trials’ themes to help setting up findings of medical research on practice has also begun [24].

In the last 50 years, basic biomedical research has prospered so much at laboratories, while clinical research per se at the bedside, consulting and surgical rooms has declined that basic research is seen as the theoretical and even as the whole medical scientific research [13,14]. Progressively, clinical research has been reduced almost exclusively to carry out essays of new high technology biochemical, radiological, genetic, immunologic, and pharmaceutical, devices and procedures. Even good clinical practice standards are being co-promoted by laboratory investigators [25]. Their outcomes and methodologies have converged closely, but only in an input-output unilateral way [26]. Recently, clinical research methodology has been absorbed by clinical epidemiology (not causal epidemiology), which has assumed the design and analysis of clinical diagnostic and therapeutic trials everywhere, not only in the population and community, but in the clinic too [20,27]. This has left the clinicians and surgeons practically with the questioned clinical judgment and interpretative methods.

This decline in the outcomes of clinical ortho-research (investigator-driven) and increased growth in meta-research (non investigator-driven), occurred in the last decades in USA, UK and Australia, while France, Germany and Japan, maintained them, possibly due to greater national research efforts [15]. For instance, clinicians in the 90ies are more than the 90% of the total US mainstream of physicians registered. Of that same total only 4% (30 000) are clinical investigators [28] not all of them scientists, more than 86% of the clinicians do not report any clinical study. The so-called countries of the South have even a worst situation [2]. Multiple causes have been involved to explain this, specially the following two: 1) Clinical practice and research have intrinsically different philosophical foundations [29], 2) Absence of active recruitment of physicians for research training at an early age [15]. From this, it could be derived that if a part of young creative MD graduates that now are going to laboratory research training, could understand clearly that clinical and whole medical science progress really need urgently the rapprochement of both research and practice, many of them would attempt to do clinical research or both successfully.

World laboratory researchers with a MD degree generally do not receive a research methodology manual for their training. They are trained one to two or more years mainly in exact sciences, molecular biology, statistics, computing, philosophy, and so on, to obtain the Ph.D. degrees, usually with basic but sometimes with applied theses too. Tutors and concrete research articles their guide. The heart of their research methodology is the experimental method assisted by biometrics techniques. Sanitary researchers with MD degrees, also make theses for MPH, MSc and/or Ph.D. degrees. They also get some guidance from tutors and research articles, but they have epidemiological and social --observational-- research method manuals based on biostatistics, and social statistics. They train one to two or more years, mainly in mathematics, social sciences, management, epidemiology, statistics, computing, philosophy, and so forth. They make few basic and much applied and participative research [20]. Clinical investigators with MD’s, usually do not study any clinical research methodology manual, except generalists in UK [30], and trialists in USA, Europe, and Japan (of its elements [31] and ethics), and have a powerless training to make MSc or Ph.D. degree theses since the undergraduate or postgraduate [15]. They are neither so guided by tutors or research articles. They received knowledge and skills of their specialties with or without clinical epidemiology, making neither research without the domain of the whole medical nor clinical research methodologies, which unfortunately are still only identified with biostatistics and computing.

The most general methodological problem that has been dragged by medical sciences is that most investigators in clinic, health system and laboratory have never seen clearly which are the central objectives and methods of modern scientific research. They still have not grasped well the concept that ideas come first and observational and experimental studies come later; that innovative ideas (scientific conjectures and hypotheses) are the sine equa non of progress in science [32], not useless philosophy. Yet they are not aware that the understanding of scientific facts with data derived from them, is only possible through the directing and ordering role of hypotheses of low, medium and high theoretical levels [14], originated generally through the use, first, of clinical judgment, interpretative and other qualitative methods of research in one subject or group of less than the so underrated ten subjects. Thus, to begin understanding a reality in the specific context of a concrete study the latter methods acquire much importance [10,11]. The dominant positivist paradigm must be complemented with the interactionist and constructivist paradigms as physics with chaos theory have been doing recently. Progressively, the dichotomized scientific research paradigms are becoming less divided [13].

There is a gap between the traditional role and models of classic disinterested, value-free - basic research, knowledge-driven, and the hired hand, consultancy - commissioned research, client-driven. Since the 18-century when the idea to provide medicine with the unit of physics surged [33], scientific medicine has hauled the methodological need to enrich those models of scientific research. This could be seen as to develop a model of new principle-directed, virtually fact-free - inductive research, synthesis-driven, which allows in the future the use of new hypotheses derived, value-laden beginning - deductive research, analysis-driven model, by analogy with the mature natural and social sciences. Therefore, over the basic and applied research developed by the hypothetical-deductive method, could be formulated subsequently by an axiomatic-like method, derived hypotheses to be proven factually [13]. However, with the development of such models, skepticism about their necessity, usefulness, and theoretical and practical difficulties, have always existed [34].

Nevertheless, this would be possible only if horizontal research about the non proportioned more used factual-inductive, hypothetical-deductive and quantitative methods, were also performed in order to established a balance with the scarcely utilized inductive-axiomatic, axiomatic-deductive, interpretative and qualitative methods, still not integrated, in a whole domain of medical methodological knowledge [13]. To achieve the unification of vertical research methodologies, it is also necessary to stress on the methods used less explicitly in mature sciences, for instance in modern physics and economics, to generate new scientific hypotheses conceptually, from high-theoretical level down to low-theoretical or empirical level --much before the operational step with the auxiliary statistical hypothesis tools--, within a unique methodological system, to increase medical, sanitary, social, and economical effectiveness of research.

At present, clinical research has been remained as an interface sort of research, with lack of man wholeness and healthfulness content, of secondhand knowledge extension and technology translation to clinical practice in hospitals and communities, generated in the research laboratories [26]. Clinical research has practically lost the direction of medical research as a whole and even clinical research per se that it had until early in the 20^th-century. To this crisis in its internal logic of progress has contributed far beyond external factors, the stress in the thought that medicine is only a non-classical science of particulars [35]. This has aborted the enormous heuristic potential of the clinical researcher and even of the studious practitioner to generate new medical scientific hypotheses not only in diagnosis and therapy, but in etiopathogeny, prevention and rehabilitation too. Clinical judgment has solely stayed and been perceived as a simple practical application of the hypothetical-deductive scientific method with the aid of probabilities to patient care [8,9,35,36], but without any possibility to formulate at least as primitively as before law-like generalizations to medicine as also a science of generals. To solve all these situations, along with the ideas of the individualized care of each patient [25], new integrative ideas about the achievement of general knowledge have to be developed too.

To understand how to develop a unified methodological system of medical scientific research, the first thing is to place this matter in its historic and logic context in a brief way. Medical sciences were born as a result of the use on the patients of the clinical judgment method, which from its very beginnings has been a more qualitative than quantitative method [7,8]. Then, the differentiation of medical science in clinical, health and laboratory sciences began with their respective scientific investigations and methods [13,26]. To date medical sciences have been developed as more theoretical or as more practical sciences with the important assistance from many mature sciences like physics, and even immature ones like psychology. The union of physicians with physicists, chemists, biologists, psychologists, sociologists, mathematicians, and so forth, has made crucial contributions to medical science progress in the opportune moments [5].

This help has given scientific methods to medical sciences to create, for medical facts, the theory they needed with a measure of certainty, aiding through medical education to achieve the goals of medical care: less suffering and illness, and more health [3,37]. However, medical science was divided in dozens of clinical and derived laboratory and public health sciences [13]. Most of the medical sciences of today study the body and its diseases through its parts: molecular genetics and biochemistry, microbiology and virologist, physiology and pharmacology, pathology, radiology, immunology, and most clinical and surgical sciences [37]. Only psychiatry studies exclusively the mind and its illnesses, but not so much its health. Sole general and family medicine are trying to study the person and his family as entire objects with their suffering, illnesses and health. Only epidemiology studies the whole communities and populations' health with their interactions [26].

Up to these days, their major solutions to the scientific problems of the different parts of the human being, have contributed with many pieces of medical scientific theories and methods by each science isolated or associated, but have not well achieved the goals of medicine [3,37]. Paradoxically, they have increased the conceptual and methodological problems, because as not well integrated contributions, they have not been suitable enough to deal comprehensibly with the complex medical facts of human being, as a whole unit or as a whole of units of investigation [13,26]. Medical methodology of scientific research due to all these reasons still has not its own body of knowledge, because it has not gone beyond the accurate and successful applications of the general scientific hypothetical-deductive and statistical-computing methods to the factual and vertical research in the clinic, health system and laboratory. This less than eclectic status is limiting the enormous potentials of progress, that medicine has [13].

This situation disintegrates the harmony of the unique creation process of medical research. This process is complete, dynamic, continuous, basic and applied. It begins in the creative medical practice in any research field and moment --clinic, health system, and laboratory--, and finishes generally in the common medical practice, only to start again, improving theory and practice iteratively. Medical researches in the clinic, health system and laboratory have to be conceived also as essentially related fields and moments of only one creative process to solve medical scientific problems, which must integrate multilaterally their methodologies to achieve more efficacy than when only they are used separately.

The results of the researches among those main fields could coincide in more or fewer distant moments, as can be understood examining just some examples. In 1747 a surgeon's mate of the Royal Navy in Salisbury, carried out what may well have been the world's first clinical trial. He demonstrated clinically with simple research that oranges and lemon juice cured scurvy. From this moment, the disease was prevented, two centuries before vitamin C was isolated as ascorbic acid, and its biochemical role elucidated by complex research [6]. In 1881 a general practitioner, also an ophthalmologist, in Havana, suggested by clinical, epidemiological and laboratory researches that yellow fever was transmitted by the female Culex mosquito [20]. No one believed in his discovery until was confirmed by many more studies carried out along with other clinician. However, his hypothesis became accepted and practiced successfully in prevention campaigns since 1900, before the isolation of its suspected virus in 1927. In 1920 a children’s surgeon and a student in Toronto, helped by a physiologist and a biochemist made another major discovery isolating insulin from dogs' models for diabetes mellitus insulin-dependent control. The thing is that now 78 years later, the omens of its control and of the insulin-resistant type derived later are not good yet. Their prevalence has increased, presumably due to the action of environmental factors, which still have not been discovered to prevent both, the diseases and its complications [5]. In 1929, a laboratory researcher described the antibacterial properties of an extract of the common mold penicillium notatun. Penicillin was given to a patient for the first time in 1941, in Oxford, after studies carried out by a pathologist and a chemist on mice models, sponsored by a modest grant of the Rockefeller Foundation [5].

Medical scientific research requires at least four conditions to be integrated methodologically in its broadest sense: First, the integration of its own philosophic, anthropologic, ethic, ontological, epistemological, logic, historic and axiologic fundamentals, also general foundation of the dominion of the methods of clinic, health system, and laboratory scientific researches. Second, the synthesis of the specific norms and skills of good common medical practice, without forgetting that also a best practice is a good theory. With its set of auxiliary and specific, scientific tools, technological and non-technological, specially, the physician-patient, physician-family and physician-community relations as medicine in themselves, among the diagnosis, prognosis, preventive, and therapeutic means too. Third, the assimilation of models and methods of health and economical organization and management, and the generation of the suitable climate to encourage creativity and discriminate good ideas, protocols, research data, scientific outcomes, and their reports, besides the quick application of the results in the current medical practice with a cost-effectiveness criteria. Fourth, the development of clinical judgment, besides new methods for the etiologic, diagnosis, therapeutic, and preventive human experimentation by computer simulation, formulation of scientific medical hypotheses, law-like generalizations, theory formation and systematization, in tight contact with the conceptual frame of medical sciences and all the levels of medical education and care of the more pressing old problems as well as of the new emerging ones.

In the eve of the 21^st-century the sleeping potential of clinical research to regenerate firsthand new scientific hypotheses, must be urgently reanimated to be further verified by clinical surveys and trials, as well as by laboratory, epidemiological and public health investigations [26]. To achieve this multilateral integration and strengthen medical research own internal logic of progress successfully, careful research must be done. The complex link between the two current scientific clinical and surgical investigations and methods, should be examined: 1) the research of a particular diagnosis and prognosis with preventive and/or therapeutic interventions (R&I), individualized in a sick or healthy person, family, community or population --through the present clinical judgment and decision making methods in the common medical and health care-- by using more quantitative research methods; 2) the general research since the one case study and initial study of few cases --applying more qualitative research methods--, to the pilot or even large surveys or trials, as well as to the study of theoretical problems, seeking for new concepts, causes and methods of research and development (R&D) of clinical care, in patients affected by one or more diseases and/or in healthy individuals --through the flourishing of the clinical judgment again as scientific method for discovery of generalities too.

The point is not to oppose clinical care to clinical research [29], nor clinical research to other medical research, neither empirical methods to theoretical and interpretative methods nor qualitative to measuring or quantitative methods, but to reconcile them in favor of science and individuals. This shall be made studying the necessary relationships between scientific theories and methods among researches in the clinic, health system, and laboratory, and the interactions and exchanges among their outcomes, coordinated precisely by the principles of the clinical R&I and R&D, to conjoin the others, because only clinical research focuses and works on the whole individual [13]. These results will provide the more robust tool to attract more and train better young generalist and specialist physicians in clinical and surgical research.

Thus, non mathematical deduction-like inferences from the new principles that could be achieved at least from empirical or low and medium theoretical levels by unconventional induction, in addition to being analytic as all deductions, could also address new ways to suggest high and low level particular hypotheses, at empirical level, conjoined with the facts [13]. General principles of clinical science knowledge through these unfamiliar analytical inferences, could give new scientific hypotheses to be tested in a case or groups of patients in R&D, as well as general principles of clinical practice could give new technical hypothesis to improve the quality of care of an individual patient in R&I in clinical medicine. These two kinds of clinical science and clinical practice heuristic methods to generate original hypotheses could probably be easier to be computerized than the ones developed to date without these general principles [13].

These ideas about unifying clinical R&I and R&D could be extended to the epidemiological and public health scientific tasks, which work with partial and whole populations of individuals. The point is to harmonize epidemiological and health programs and management with epidemiological and health research. These ideas seem to be not so adequate for the basic over medical models or technological research laboratory tasks that usually make full-time R&D. Nevertheless, R&I could be accepted partially concerning clinical and sanitary laboratories investigations, because they make the research of the preceding and subsequent states of their subjects to the interventions, which are derived from outside the laboratories: the clinic and public health fields. In addition, it can be said that the successes from R&D in all medical scientific fields are or have to be introduced into medical practice improving the quality of the R&I in the clinic and the public health, from where almost all of them were born at least in a first instance.

Recently, "The Goals of Medicine", an international theoretical research project of the US Hastings Center and 13 countries, in cooperation with the World Health Organization, established priorities for its long-term progress, and stated to do imperatively reforms in medical research [3]. Really, there are big gaps of scientific knowledge and methodology about medical research, which must be filled in. In the world, conjoined endeavors through jumbo projects have to continue, but in all medical research fields aimed at helping the improvement of whole medical research. About the first reform, which is to improve medical research using both of the dichotomized medical research paradigms, there has been since 1994, an international theoretical project in preparation called firstly "Human Health", which deals with this matter [13]. Concerning the second reform, to increase clinical medicine, epidemiological and public health researches, besides, the extraordinary laboratory research "Human Genome Project" designed at the end of the 80ies [5,38,39], and the "Human Brain Project" [40], also is necessary to do other multinational projects in those fields [3], but integrating them hierarchically. For almost fifty years something has been lacking such as a "Human Healthy Life Project" [41,42], with at least the following subprojects: "Causes and Reasons for a Healthy Life", "Needs and Means to Improve Lifestyles", "What is Good Health Care and How to Give It"? And so on, stressing on anthropology, psychology, demography, sociology, social epidemiology and economy, but never forgetting the crucial role of biomedical, genetic and environmental epidemiology and other health sciences too.

Nevertheless, these last efforts will not be enough to satisfy the present and future needs of national and international medical research, education and care worldwide. This is because, laboratory and sanitary researchers cannot make the indispensable research of the dormant huge mass of clinicians and surgeons to personally solve health problems of the entire person: unattainable top frontier of the laboratory research and essential operational unit and last objective of public health research. The clinic (clinical and surgical offices and rooms) is the research field that potentially in any nation and in the world could produce contributions from at least one fifth --20% on average from 10% to 30%-- of the physicians that work in clinical practice, to improve it. This concept is very important, if it is analyzed within the context of the USA data [28] exposed above. There exists even a better potential for clinical research within nurses and other health professionals of the world, because almost all of them work in clinics and could contribute even more with research outcomes in regards to improving clinical care too. Therefore, it is very necessary to make also some international clinical and surgical research projects as complex as the genome project, but that will probably not require so much high-cost technology.

In this sense a "Human Medicine Project", could fulfill some essential needs of knowledge and methods in the hospital and community, with at least the following subprojects: "Unification of Alternative with Scientific Medicine" (Eastern and Western Medicine) [43], "Conception of General and Special Clinical and Surgical Medicine Self Research Spaces", "Creation of New Family Medicine Research Spaces" [26], a "Health Classification" --from Good or Satisfactory (+) Health through Non Illness-Non Disease Suffering down to Unacceptable or Bad (-) Health--, according to the phases of the life cycle of the person and his family [13]. It should take very hard work to unify three of the main dichotomized medical research paradigms: humanism-science, body-mind and disease-health [13]. However, simultaneously, the critical mass of clinical investigators has to be increased and better prepared than ever. Working on the flourishing of the clinical judgment as scientific discovery method of generalities again, could be the most powerful way to attract more young generalist and specialist physicians, giving them a much better training concerning both clinical and surgical research and practice. Clinical and surgical researchers and his educators must carefully study the experiences of robust scientific training in last decades of laboratory and sanitary researchers. For instance, this could be achieve studying the training programs for basic laboratory researchers applied in the US National Cancer Institute, Oxford Institute for Molecular Medicine [5], and so forth, and the training for sanitary researchers in the John Hopkins School of Public Health, Center for Disease Control and Prevention, and London School of Hygiene and Tropical Medicine, and so on [20].

For some decades, both the US Robert Wood Johnson Foundation in the Yale University School of Medicine and other schools, and the Rockefeller Foundation in some medical schools at home and abroad (like in China), have been strengthening clinical research respectively, with programs to prepare good clinical specialists and clinical epidemiologists to make better randomized clinical trials [20]. However, due to all the previous analysis of clinical and surgical research weaknesses, the new model of training proposed has to exceed these important efforts, and be more powerful in order to approach a broader spectrum of ortho-research through its own initiative. Clinical research training has to receive more than the hypothetical-deductive, Gaussian, Bayesian, and non parametric statistics, computing, artificial intelligence, decision making and cost-effectiveness methods, as well as human experimentation by computer simulation; along with clinical trials meta-research and its ethics. A nucleus for the beginning of this work could be a unified methodological approach research education course program developed since 1995 [44]. They ought to receive mainly two handbooks: One of a unified medical research methodology, and another about a broad clinical research methodology, in a research training of one to two or more years to obtain with a thesis a Master in Clinical Science (MCS) or a Ph.D. degree, before, beginning or after the generalist or specialist training. It must also include mathematics, genetics, anthropology, psychology, sociology, social epidemiology, full uses of Internet WWW and E-mail for clinical research, education and practice, and specially philosophy of medicine, including ethics, ontology, and epistemology. For nurses and other health professionals, the program could be modified attending to their specific profiles and requirements.

An international pilot school or institute, could be established somewhere within some institution, under the direction and coordination of the World Health Organization, with funds from different international sources. This institution could be aimed to research and elaborate didactic materials and educate postgraduates in this new conception of whole medical research process, including the clinic, laboratory, and public health; guided by a unified methodological system of scientific research, to rescue and strengthen the complete internal logic of progress of medical research and not only of one or two fields. The programs of courses, workshops and conferences, would be very important not only to be taught and studied by clinical and surgical researchers, but also by sanitary and laboratory researchers, as well as by health research policy makers and medical research industrial managers worldwide.

This school or institute could be the head coordination center in the country selected, carrying out clinical medicine and public health jumbo projects. Its subprojects could be coordinated with different peripheral centers in other countries. Later, previous or simultaneously with this experience, it is also possible to set inside or outside of the above institution, another international pilot clinical ortho and meta-investigation school or center, to begin to research, elaborate didactic materials, and prepare clinical and surgical researchers with a more solid background, creative skills [45] and a broader scope than the trialists have, in order to develop more clinical and medical science. The analysis of the results obtained with this trans-methodological research model beginning with the postgraduate programs, should be a guide of how to introduce it into the undergraduate curriculums of medical, nursing and other health professional students. International exchange through Internet and new communication technologies of enough scientific methodological information without high-cost technologies [40,46] could solve many communication problems that would have made such projects impossible to be carried out in the past.

The practical application of this unified methodological approach for a medium and long-term, along with a greater use of the present and future separated research methodologies, from the student, scientist, physician, nurse and other health professionals, up to the medical organizations of center, basic, clinical and industrial laboratories, as well as university, nation, region and world, might become very significant. It could be vital for a yearly saving of trillions of days of peoples suffering from maladies, and of hundreds of billions of useful life years lost by premature disabilities and deaths, as well as of hundreds of billions of dollars spent worldwide, by the state and private agencies, laboratories and companies, and non governmental organizations.

1. World Health Organization. Medical Research. Priorities and Responsibilities. [Proceedings of a Round Table Conference Organized by CIOMS with the Assistance of WHO and UNESCO, Geneva 8-10 Oct. 1969]. Geneva: WHO Scientific Pub, 1970.

2. World Health Organization. A Research Policy Agenda for Science and Technology to Support Global Health Development. Synopsis and Background Document of WHO Research Policy Strategy Division and Advisory Committee on Health Research, Geneva: WHO Scientific Pub, 1997.

3. Callahan D. The Goals of Medicine. Setting New Priorities. An International Project of the Hastings Center. Hastings C Rep 1996;Spec Suppl:S1-S27.

4. Engelhardt Jr HT. The Foundations of Bioethics. 2^nd ed. New York, NY: Oxford University Press, 1996.

5. Weatherall D. Science and the Quiet Art. The Role of Medical Research in Health Care. 1^st ed. London, UK: W.W. Norton & Co., 1995.

6. Temple NJ. Medical research - A complex problem. In: Temple NJ, Burkitt DP, eds. Western Diseases: Their Dietary Prevention and Reversibility. 1^st ed. Totowa, NJ: Humana Press, 1994;419-436.

7. Matthews JR. Quantification and the Quest for Medical Certainty. 1^st ed. Princeton, NJ: Princeton University Press, 1995.

8. Feinstein AR. Clinical Judgment. 1^st ed. New York, NY: RE Priege Pub. Co., 1967.

9. Feinstein AR. Clinical Judgment revisited: the distraction of quantitative models. Ann Intern Med 1994;120:799-805.

10. Kelner MJ, Taylor KM. Strengthening medical research through an integrated approach. Acad Med 1995;70:566-567.

11. Baum F. Researching public health: behind the qualitative-quantitative methodological debate. Soc Sci Med 1995;40:459-468.

12. Eisenberg L. Science in medicine: Too much or too little and too limited in scope? Am J Med 1988; 84: 483-491.

13. Stüsser RJ. Complex induction of unifying principles to assist the formulation of medical and health integral hypotheses. In review in a Journal.

14. Wulff HR, Pedersen SA, Rosenberg R. Philosophy of Medicine: An Introduction. 2^nd ed. Oxford: Blackwell Scient., 1990.

15. Farrel GC. Career paths for clinical scientists. J Gastroent Hepatol 1996;11:891-894.

16. Feinstein AR, Koss N, Austin JH. The changing emphasis in clinical research. I. Topics under investigation: an analysis of the submitted abstracts and selected programs at the annual "Atlantic City Meetings" during 1953 through 1965. Ann Inter Med 1967;66:396-419.

17. Fletcher RH, Fletcher SW. Clinical research in general medical journals. A 30-years perspective. NEJM 1979;301:180-183.

18. McDermott MM, Lefevre F, Feinglass J, Reifler D, Dolan N, Potts S, Serger K. Changes in study design, gender issues, and other characteristics of clinical research published in three major medical journals from 1971 to 1991. J Gen Intern Med 1995:10:13-18.

19. Susser M. Causal Thinking in the Health Sciences: Concepts and Strategies of Epidemiology. 1^st ed. New York, NY: Oxford University Press, 1973.

20. Buck C, Llopis A, Najera E, Terris M, eds. The Challenge of Epidemiology. Problems and Selected Lectures. Washington, D.C.: PAHO/WHO, Scientific Pub. 505, 1988.

21. Lafferty KJ. Annual Report 1995. John Curtin School of Medical Research. The Australian National University. Canberra, National Capital Printing, 1996.

22. Simes RJ, on behalf of the PPP and CTT Investigators. Prospective meta-analysis of cholesterol-lowering studies: The Prospective Pravastatin Pool (PPP) Project and The Cholesterol Treatment Trialists (CTT) Collaboration. Am J Cardiol 1995;76:122C-126C.

23. Selway CN, Terrett NK. Parallel-compound synthesis: methodology for accelerating drug discovery. Bioorg Med Chem 1996;4:645-654.

24. Hunter DJW. The Cochrane Library 1996 (CD-ROM). Can Med Ass J 1997;156:1751-1752.

25. LeQuellec A. Clinical research in hospitals and daily care for patients: The risks of an imminent divorce. Revue Med Intern 1996;17:283-285.

26. Stüsser RJ. The creation of new family medicine research spaces. In review in the WHO.

27. Susser M. Editorial: The tribulations of trials--intervention in communities. Am J Public Health 1995;85:156-158.

28. Hovde M, Seskin R. Selecting U.S. Clinical Investigators. Appl Clin Trials 1997;8:34-42.

29. Ward M. Myths and realities in clinical research. J Gastroent Hepatol 1996;11:887-891.

30. Howie JGR. Research in General Practice. 2^nd ed. London, UK: Chapman & Hall, 1992.

31. Friedman LM, Furberg CD, DeMets DL. Fundamentals of Clinical Trials. 3^rd ed. St. Louis, Mo.: Mosby-Year Book, 1995.

32. Horrobin DF. Orbituaries: Linus Pauling and Karl Popper. Med Hypotheses 1994;43:43:359.

33. Bole TJ. John Brown, Hegel and Speculative Concepts in Medicine. Texas Rep Biol Med 1974; 32:288-297.

34. Shaffner KF. Theory change in immunology part 1: Extended theories and scientific progress. Theor Med 1992; 13:175-182.

35. Engelhardt Jr HT, Erde EL. Philosophy of Medicine. In: Durbin PT, ed. A Guide to the Culture of Science, Technology, and Medicine. 1^st ed. New York, NY: Free Press, 1980:364-461.

36. Murphy ER. Logic of Medicine. 1^st ed. Baltimore, Mar.: The John Hopkins University Press, 1976.

37. Engel GL. Physician-scientist and scientific physician. Resolving the humanism-science dichotomy. Am J Med 1987;82:107-111.

38. US Dept. of Health and Human Services, US Dept. of Energy. Understanding Our Genetic Inheritance. The US Human Genome Project: The First Five Years, FY 1991-1995. Springfield, Va.: National Technical Information Service, NIH Pub No. 90-1590, 1990.

39. Engel LW. The Human Genome Project. History, goals, and progress to date. Arch Pathol Med 1993;117:459-465.

40. Miller PL, Nadkarni PM, Kucherlapati R, Krauter KS, Kidd KK, Ward DC, Shepherd GM, Berkowicz D. Network-based informatics support of research collaborations in the Human Genome Project and the Human Brain Project. Medinfo 1995;8:1541-1544.

41. United Nations Organization. Report on International Definition and Measurement of Standards and Levels of Living. New York, NY: United Nations Pub., 1954.

42. World Health Organization. Measurement of levels of health. Technical Report Series 1957;132:6.

43. Stalker DF. Evidence and alternative medicine. Mt Sinai J Med 1995;62:132-143.

44. Stüsser RJ. Medical Scientific Research, Intervention and Development at the Clinic, Health System and Laboratory. A Unified Methodological Approach. . In review in the WHO.

45. Meyers MA. Science, creativity, and serendipity. Am J Roentgenol 1995;165:755-764.

46. Peters R, Sikorski R. Digital dialogue: sharing information and interests on the Internet. JAMA 1997;277:1258-1260.

Rodolfo J. Stusser, M.D.

Integration Science Program for Medicine, Nursing, Technology & Health
Back to the Index Page