Search

The cost of research and development (R&D) for a new medicine is an essential element in the debate about fair prices. In a recent study, we estimated R&D costs at an average of around 1.1 billion euro per drug; that is a lot of money, but more than 50% lower than the usual estimate of 2.4 billion euro. There is a need for more transparency about R&D costs, so that proposed prices for medicines can be better assessed on their fairness.

The ultimate aim of investigations into the costs of research and development (R&D) is to inform societal discussions on drug affordability. The premise is that knowing R&D costs will help when setting 'reasonable' drug prices. While high R&D costs may explain why prices are high, these costs need not justify paying those prices when health gains are limited. Value-based pricing models that explicitly take health gains into account also have limitations, most notably that they ignore R&D costs and consider prices to be 'reasonable' simply because other high costs of care can be avoided. Both cost-based and value-based pricing models are necessary to determine whether prices are reasonable; however, redesigning the drug innovation ecosystem could bring a more relevant contribution to reasonable drug prices than evaluation of the reasonableness of the price.

In 1999 the Advisory Council on Health Research reported that research in mental health care in the Netherlands was poorly developed in comparison to other medical disciplines. In response, The Netherlands organization for health research and development (ZonMw) initiated a euro 24 million stimulation programme over a 10-year period, which started in 2003. Long-term follow-up studies were initiated for anxiety and depressive disorders (NESDA), psychotic disorders (GROUP) and child psychiatric disorders (TRAILS, Generation R). In addition, 41 practice-oriented projects and 35 PhD projects were funded. The programme has resulted in four unique databases, a multitude of additional grants and a large number of international publications and PhD theses. Perhaps more importantly, many clinical practitioners had the opportunity to participate in research projects and to develop a more critical and evidence-based attitude. The programme demonstrates that financial stimulation can effectively improve the practitioner's evidence-based attitude.

The NOSTRADAMUS study (ISRCTN07836779) was prematurely terminated due to low inclusion rates. There were several causes for this low inclusion: delay of approval by medical ethics committees, competition with industry-initiated intervention studies with a higher financial compensation, and the lack of study staff and allowance of expenses. We advise restraint with respect to testing for thrombophilia in patients with a first deep vein thrombosis or pulmonary embolism, as the benefit of this procedure has yet to be demonstrated.

The pharmaceutical industry is not basically interested in knowledge about diseases and their treatment--its main interest is selling drugs. Hence, its research may even be aimed at shifting the border between health and disease in order to produce more indications for which drugs can be prescribed. In contrast, non-industry sponsored research can be aimed at solving medical problems that really matter and problems for which other forms of treatment are indicated than medication. Therefore, industry-sponsored research is bad for medical science.

The conflicts of interest dominate discussions on collaborative research between academic institutions and the pharmaceutical industry. Although one should not be blind to such possibilities and remain critical, the advantages outweigh the risks by far. The remaining diseases for which adequate pharmacotherapy is lacking are complex and require an expensive research infrastructure. Therefore, progress will benefit from collaboration and should not be hindered by short-sightedness.

Psychotropic medication has brought about far-reaching changes in psychiatry: in its nature and practice, its image of man and its public image. Never before have so many psychotropic drugs been prescribed for young people. 'Difficult' children are now referred to as ADHD children and moody youngsters are given antidepressants. In adult psychiatry treatment is being dictated more and more by protocols and guidelines: very often medication is the treatment of choice. The reasons for this are largely economic. Increasingly 'research' is being sponsored by the pharmaceutical industry. Published research results are often skewed so as to favour the sponsor. Some scientific journals owe their survival to drug advertisements. Even some patient organisations are supported by the pharmaceutical industry. How will psychiatry and mental health care be able to escape from this 'straightjacket' in the future? The purpose of this polemical essay is to draw the attention of health care professionals and researchers to this rather worrying development.

Biomedical science in the Netherlands and other continental European countries is lagging behind scientific research in English-speaking countries. A comparison between the two systems reveals several crucial differences. Although levels of government funding of scientific research are approximately equal, the rigid, non-quality-based funding system of continental universities compares badly with the flexible quality-based funding systems in the USA and the U.K. The rigid, hierarchical organisation and indistinct career structure that are found in the continental European system lead to problems in funding strategy and a lack of independence among young researchers. Moreover, equalized funding by national governments to state universities has hampered the creation of centres of excellence. It is proposed that the broad introduction of a peer-review-based funding system would solve these problems and would put European science back on its feet.

Despite over 1,000 randomised controlled trials (RCTs) evaluating the efficacy of antidepressants, their effectiveness in important subgroups of depression is almost unknown. Around 40% of patients with depression do not respond to treatment with selective serotonin-reuptake inhibitors, the most frequently used type of antidepressant in The Netherlands. Only 3 RCTs have studied whether another type of antidepressant is effective in these patients. Two other examples are psychotic depression and bipolar depression. While these conditions account for 15% and 20% of all depressed patients, respectively, their treatment has been studied in only 10 and 12 RCTs, respectively. The main reason for this lack of research is lack of funding. Therefore, it is argued that a special Dutch research programme for comparative drug studies is warranted. Funds for such a programme should become available from The Netherlands Organisation for Health Research and Development (ZonMw), the pharmaceutical industry and health-insurance companies.

Less money is spent on medical research in the Netherlands than in other industrialised countries, even though Dutch science, and certainly Dutch medical science, scores qualitatively among the best in the world. Part of the explanation is that a relatively large part of scientific research in the Netherlands is financed directly by the government. As a result of several rounds of cutbacks in government spending, that were executed each time by cutting research that performed less well, the remaining research groups are at high qualitative level and highly competitive. In countries that surpass the Netherlands, there is an important second stream of government funding via Medical and Health Research Councils. In the same countries, the pharmaceutical industry also provides more money for medical research. The other side of the coin is that medical research in those countries seems more or less 'for sale'. Too heavy dependence on market oriented research leads to doubts regarding the independence of medical research. International observers judged that the direct financing of research by government in the Netherlands was an enormous bonus since it leads to flexibility to start new topics and at the same time stability of positions. However, a major concern for Dutch science is that there are too few possibilities to attract and hold promising young people. It is especially difficult to keep promising young women; though this is true for all industrialised countries, the Netherlands lags behind its major competitors as far as the position of women in the higher ranks of science is concerned. These problems will have to be solved by stimulation programmes for young researchers and flexibility of the higher echelons. The educational system must not be directed only at the production of more doctors for medical practice, but also at sufficient scientific training for these doctors so that they will be able to comprehend new developments. The ordinary daily practice of medical science is to verify the usefulness of new developments--which is just as important as breakthroughs at the top. This means that there should be new investments, not only for top ranking scientists in fashionable areas, but also to maintain sufficient numbers of medical scientists at all levels. It cannot be foreseen where the next new developments will arise, and even in a small country, active research should be ongoing in many areas to maintain contact with the international research community. New investments should primarily be in direct government financing and in augmentation of streams of money via Medical and Health Research Councils.

Objective: To compare the expenditures on health research in the Netherlands with those in other Western countries., Design: Descriptive., Method: The expenditures on health research in 1997 were determined for the Netherlands, the United Kingdom, Germany, Norway, Denmark, Sweden and the USA and subsequently classified into: governmental funding for research in medical faculties or clusters; grants from MHRCs and other bodies; and private funding from industry and charities. The sources of information were the total research budgets 2002 of the Dutch Ministry of Education, Culture and Science, annual reports from charities, the Dutch Central Statistical Bureau and, for foreign countries, MHRCs or comparable institutions., Results: In 1997, the Netherlands spent the equivalent of 855 million US dollars on health research (extremes of the investigated countries: 382 (Norway)-32,283 (USA)). This was less than in the other countries, whether calculated per capita, in US dollars (55 (Netherlands)-159 (Sweden)), as a promillage of the gross national product (2.27 (Netherlands)-5.84 (Sweden)), or as a percentage of the total expenditures for health care (2.62 (Netherlands)-7.54 (UK)). Especially the industrial expenditures on health research in the Netherlands were low, but the governmental expenditures were also lower than in the other countries.

The editorial board of the Nederlands Tijdschrift voor Geneeskunde (Dutch Journal of Medicine) has decided to disclose at the end of each article conflicts of interest (financial and otherwise), the sponsor of the research or its publication, and whether the authors were independent in their investigations, analysis and reporting of the data.

In 1995, the Health Research Council of the Netherlands (RGO) published a report on the efficiency and efficacy of medical research in the Netherlands. One of its conclusions concerned the formation of multidisciplinary research institutes around various themes. The medical faculties and university hospitals responded by forming integrated university medical centres, which placed a considerable emphasis on patient care during their first few years of existence. However, the deans of the respective medical faculties realised that these organisational changes might form a threat to fundamental research, due to a lack of financial resources. They produced a common statement to protect and support fundamental research. This was discussed at a meeting of the Royal Netherlands Academy of Arts and Sciences in December 2000. Several speakers addressed the question as to whether (fundamental) research in these university medical centres should be regulated in a 'top-down' manner whereby directions and priorities are formulated by a centre's management, or whether the (clinical) researchers should formulate the direction of the research ('bottom-up'). Managers wanted a 'top-down' approach and researchers a 'bottom-up' approach.

The 'Ethiopia-Netherlands AIDS Research Project' (ENARP), started in 1994, is a long-term collaboration between AIDS researchers in Amsterdam and the Ethiopian Health and Nutrition Research Institute in Addis Ababa. The ENARP's primary objectives include conducting studies on HIV and AIDS in Ethiopia, especially by means of some large-scale prospective cohort studies, training Ethiopian scientists in PhD programmes in epidemiology, immunology and virology and establishing a reference laboratory for HIV and AIDS in Ethiopia and neighbouring countries. External funding for ENARP amounts to 32 million Dutch guilders for two periods of four years and is being provided by the Dutch Government. ENARP is the largest third world biomedical project supported by the Dutch Government. In 2000 two Ethiopian students obtained their doctorates from the University of Amsterdam. Five new PhD students commenced their training in 1999. ENARP hopes to set up HIV-1 vaccine phase I and phase II trials in the near future.

A number of aspects must be kept in mind when interpreting cost-effectiveness ratios; it is important to realise, for example, that a cost-effectiveness ratio is a relative and not an absolute measure of efficiency. A cost-effectiveness ratio always involves a comparison of two interventions; therefore, the choice of the competing alternative has great impact on the reported, 'incremental', cost-effectiveness ratio and requires careful study. Furthermore, a cost-effectiveness ratio is meant to support a choice or decision. A check must be done to see whether the study context and the resulting cost-effectiveness ratio are appropriate for the choice or decision under consideration.