Barriers to conducting clinical research in reproductive medicine: Latin America Fernando Zegers-Hochschild, M.D. Unit of Reproductive Medicine, Clinica las Condes, Santiago, Chile
Societies in Latin America are not scientifically driven and therefore, the allocation of human and economic resources to research is meager, as a reflection of this as well as other cultural and economic realities. (Fertil Steril 2011;96:802–4. 2011 by American Society for Reproductive Medicine.)
Latin America is a puzzle of 20 countries with a variety of economic, social, and cultural identities, which strongly influence the way science, and technology, is perceived by society. In the majority of countries, decisions are triggered by emotional and religious influence rather than using the evidence provided by science and technology. In Chile, the public discussion in areas such as embryo cryopreservation and emergency contraception (EC), has been centered almost exclusively in whether the ‘‘rights of embryos’’ were adequately protected, when exposed to the risks of freezing in IVF or the risks of impaired implantation in (EC). The rights of women to prevent multiple births while maintaining reproductive efficiency, and the right of adolescents to avoid unwanted pregnancies received very little attention, in spite of the fact that among other problems, the prevalence of adolescent deliveries is 19% of all births. Societies in Latin America are not scientifically driven and therefore, the allocation of human and economic resources to research is meager, as a reflection of this as well as other cultural and economic realities. In order to answer this survey, five regional directors of the Latin American Network of Assisted Reproduction (www.Redlara.com) were asked to give their opinion from a regional perspective. Whenever needed, regional similarities and differences will be mentioned. From another perspective, we asked Fertility & Sterility to provide the names of institutions and country of origin of publications from Latin America during 2009 and 2010. Only 73 communications were published in these two years; 49 (67%) from Brazil, 13 (17.8%) from Argentina, and 11 (15.1%) from Chile. Overall, 40% of these contributions correspond to clinical research while the majority of them are basic research resulting from universitybased institutions. It is worth mentioning that altogether, 206 papers were submitted (which include 4 from Peru and 2 from Colombia). Thus, 68% of studies submitted for publication by Brazil and almost half of those submitted by Argentina and Chile were rejected. There are many possible reasons for this inefficiency in communicating research findings. One possibility is poor quality of research, another is poor capacity to communicate good quality research, due to language barriers and inexperience in scientific writing. Whatever the reasons, when submissions are repeatedly followed by rejection, there is a feeling of frustration and many of these studies are then published in Spanish or Portuguese and never reach the English speaking reader.
Received August 31, 2011; accepted August 31, 2011. F.Z.-H. has nothing to disclose. Reprint request: Fernando Zegers-Hochschild, M.D., Unit of Reproductive Medicine, Clinica las Condes, Lo Fonticella 441, Santiago 6770128, Chile (E-mail: [email protected]
What do you see as the most significant barriers to research? There are four significant barriers to research. First, there are limited funds allocated to research and development. The amount of economic resources and facilities allocated to research influence scientific productivity but most of all, they contribute to increase the critical mass of scientists, which at the end of the day, make science progress by a factor greater than 1. There is a great disparity in the proportion of GDP that different countries allocate to research and development (Fig. 1). There are many reasons for this disparity and dealing with basic needs, such as the prevention of maternal death, infant mortality and fertility regulations occupy a great deal of the wealth of every developing country. Thus, resources for science and technology are not a priority in Latin America as it is in a large proportion of countries in Europe and Asia. Furthermore, the total amount of public funds available for health research show enormous disparity between some wealthy countries and countries in Latin America. In the U.S., the budget of the National Institutes of Health alone is in the order of 31 billion USD; and a similar organization in Japan assigns 24 billion, and 17.5 billion USD in Sweden. In Latin American countries, the budget of the national agencies for research is in the order of 400 million USD in Argentina and Chile, and 2.6 billion USD in Brazil; which partly explains the larger scientific productivity of Brazil when compared with the rest of Latin America; but it also explains the abyss between scientific productivity in rich and poor countries. In the last decade,
FIGURE 1 Expenditure on research and development as percentage of GDP, 2008 or latest available year.
Zegers-Hochschild. Conducting clinical research in Latin America. Fertil Steril 2011.
Fertility and Sterility Vol. 96, No. 4, October 2011 Copyright ª2011 American Society for Reproductive Medicine, Published by Elsevier Inc.
Brazil has placed considerable efforts in diverting funds for research, and this policy is starting to flourish; in fact, today Brazil is one of the 5 countries having the most abstracts accepted for the Annual Meeting of the ASRM. This is an example of how promoting and facilitating research increases the scientific critical mass of researchers and their productivity increases in similar proportion. Second, there is limited capacity to conduct research studies and inexperience in scientific writing. All regional directors agreed there is a lack of appropriate education and training in devising and conducting research protocols in reproductive medicine. Research is not part of an active curriculum in the majority of medical schools nor in post graduate training activities. This capacity is built mainly through sporadic tutorial activity. Furthermore, English, as a scientific language is more than just being able to write in English; it has to do with structure and precision in the way ideas are expressed. Acquiring this capacity can take quite awhile and constitutes a serious handicap when English-speaking scientists review papers from Spanish or Portuguese speaking professionals. Third, institutions providing service with modern reproductive technologies are mostly situated in the private sector; less than 10% are university based. Although many of these private institutions have the capacity and facilities to conduct clinical and applied research, there is little motivation and stimulus or technical assistance to do research. In spite of this, approximately 40% of the clinical research published in Fertility and Sterility derives from private institutions. Fourth, the type of research that can be done in reproductive medicine is also influenced by law and religion. There is strong influence of Catholic morality, which states that personhood begins with fertilization. As such, the use of human embryos for stem cell research is not possible. This is indeed a limiting factor for research in this revolutionary field. Do institutional review boards/ethic panels, represent a significant barrier to your research? In general, institutional review boards and ethic panels are very apprehensive with research initiatives, which have to do with preimplantation embryos and/or women treated with ART. Several regional directors expressed that when it comes to reproduction, decisions by institutional review boards are politically motivated. They all agreed on the benefit of having an external body to evaluate whether ethical principles such as non-malefiscence, autonomy, and justice, were appropriately taken care off, however, most believe that institutional review boards represent a difficult barrier and take a mean of 4 to 6 months before a project is cleared. From a personal perspective, after discussing research projects with several ethic panels in Chile, I believe the most difficult barrier is the use of a morality influenced by religious beliefs instead of secular morality which centers the objective in how well are risks and benefits taken care for the protection of research individuals. Furthermore, in many private institutions, ethic panels depend on higher institutional authorities, such as board of directors or medical directors. In this way, their judgment is influenced by the balance between risks and benefits for the institution rather than the scientific and ethical merits of the research itself. How are research personnel and projects generally funded? How much research is self-initiated as opposed to solicited by industry or pharmaceutical companies? Most research projects in Latin America are self-initiated, with little funding. There are few institutions outside universities, which have professionals where part of their time is allocated to clinical and/or basic research. The reality in most private institutions and in univerFertility and Sterility
sities is that the initiation of research projects is the result of good will and curiosity more than the availability of funds. As opposed to most Latin American countries, in Brazil, several federal or state foundations promote and fund research initiatives, which contributes to the formation of young clinicians. In general, multicenter research offered by pharmaceutical industries are well received because they provide funds for young scientists and contribute to ‘‘group working’’, however, in recent years the research contracts have become extremely complicated when it comes to insurance and other international regulations which are sometimes difficult to accept by the institution where research is to take place. Do the hospitals and medical facilities where you do research represent a barrier to your research (e.g., by charging you for use of facilities), are they neutral, or do they actively support your research efforts? In general all institutions, public and private, recognize an added value when they are involved in research and subsequently recognized in scientific publications, but there are no facilities to do research. Clinicians do not have time allocated for research or scientific writing. There are few institutions with secretarial assistance to help in the review of literature and writing. All this additional work is mainly done by the staff, after hours and during week-ends. In the clinical field, there is little correlation between the number of research projects and academic positions. Although there is no specific cost for the use of clinical and laboratory facilities, many institutions charge an overhead, which is 10 to 15% of the budget excluding the costs of equipments. What challenges do you face in recruiting research subjects? There are no challenges in recruiting research subjects except for the time taken to explain the type of research to a person who is simultaneously being part of a medical treatment. In general, the clinician does the first recruitment and the research subject/patient is sent for an appointment with the research coordinator for a full explanation of the purpose of the study, the risks and benefits and the review of consent forms. Could you describe the informed consent process you generally follow? Is the principal investigator allowed to consent his/her patient to participate in a trial and is the principal investigator allowed to treat the patients once enrolled in the trial? In a research team, there are a restricted number of professionals allowed to discuss consent forms with research subjects and most of the time it is the principal investigator and a professional acting as a research coordinator. The review of consent forms with research subjects/couples, follows a thorough explanation of the type and purpose as well as their role in the study. This is followed by the potential risks involved as well as benefits for themselves or for humanity. Compensation is also discussed when participation requires time and absence of work. Consent forms used in my institution follow guidelines adopted by the World Health Organization. A principal investigator or associate investigator can recruit one of his patients as research subject; but the actual review of the project and the process of consent are done by another professional. After agreeing to participate, the responsible clinician can be part of the research staff. What if any, are the barriers to collaboration in multicenter trials? There are no special barriers to collaborate in multicenter multinational trials in Latin America. In fact, the Latin American Registry
of ART which includes 145 centers in the region is a vivid example of multicenter multinational research which has been ongoing for 21 years. Other examples of multicenter research studies conducted by Redlara can be found on its website (www.Redlara.com). The major difficulty in participating in multicenter research sponsored by pharmaceutical industries is the lack of flexibility to adapt legal contract to each local reality. Many institutions are reluctant to contract insurance policies that will fit with the sponsor’s regulatory needs. At least, in my institution, this has proved to be a barrier. How are junior investigators trained in doing research? Are investigators required to have specific training by institutional review boards? As referred before, most of the training of junior investigators is tutorial and a large part of their actual training in research results from their involvement as research as co-investigators in clinical trials. Because there is no formal education in research, very few young professionals bridge the gap between the ability to participate as research assistants and being capable of writing a research proposal. Are you prohibited from doing some types of research? In my country as in the majority of Latin America, any research that involves the death of embryos is not accepted. Stem cell research using human embryos, or any form of cloning of human embryos is unlawful. Furthermore, in many countries, PGD cannot
be performed because even chromosomally abnormal embryos cannot be destroyed. If you could, what would you change to enhance research opportunities and productivity? I propose the establishment of a north-south program for the strengthening of research capacity consisting of a network of institutions from developed countries with strong academic background, and willing to collaborate in providing short term (%6 months) research training to young scientists and/or clinicians from academically strong institutions in developing countries. In this north-south interaction, young scientists and clinicians from institutions in developed countries should also benefit by working under different social and cultural settings. These ‘‘twin institutions’’ bridged by the relationship established with these visiting professionals, could start collaborative research through multicenter/multinational research trials in areas of mutual interest. Funds for travel and accommodation could perhaps be available through educational grants from the industry and pharmaceutical companies as well as other non-govermental organizations. Furthermore, this program could be administered and coordinated by a working group within ASRM. As part of this north-south initiative, small group learning activities to acquire tools for ‘‘scientific writing’’ should help in getting research studies published in English speaking journals.
Conducting clinical research in Latin America
Vol. 96, No. 4, October 2011