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Rev. Bras. Anestesiol. vol.57 no.3 Campinas May/June 2007
Clinical research on pediatric patients
Careful and conscientious observation of the facts has always been used to acquire scientific knowledge in medicine. Thus, two other words are implicit in the word research: search and investigation. To search and investigate a certain knowledge. However, scientific research is based on the obedience to the method, the proper way of communicating the results, and the technique. Therefore, systematization with the production of reproducible and, more important, reliable knowledge should follow at least three requirements: 1) there is no "I think" or "my research". There is only the information or lack of it; 2) results are not invented, protocols are not modified to adjust themselves to the results, and there are no false-true results; 3) it is absolutely necessary to obey ethical norms and laws regarding research, both in animals and in human beings. If anyone of these requirements is not fulfilled, the research should be rejected.
Respected scientific journals, frequent sources of citations, have an Editorial Board to help the Editor chose the works to be published. Those Boards analyze carefully the material submitted by the authors and almost always stop the publication of works that have in some way not respected the three requirements mentioned above or present methodological mistakes that affect the integrity of the results. The stricter the criteria applied by the journals, the greater the reliability of the articles published. This is almost always related to the number of times the articles of such journals are quoted by other authors, constituting what is called the "impact". Not every publication is trustworthy. One can find trash everywhere and in every language. Among Brazilian medical authors it is common, perhaps due to the colonialist influence, the pride to have their work published abroad, in English, in any journal. What matters is in which journal it was published and how many times the work was quoted. For authors, to have their work published in important journals brings the reputation and respect of the results obtained. Since they are not aware of those facts, or because they did not have any scientific training, many authors are annoyed when some of their works are rejected by serious journals. But their attitude should be the opposite: they should take advantage of the experience to redo their method and verify where a mistake was made. Almost always the reviewers offer their opinion. To read and observe them with criteria can be useful to improve the results and methods of the research. Scientific research is rational by definition, and there is no space for emotion. Once, an aspiring writer asked the advice of the great Irish writer Oscar Wilde. Facing with his annoying question, he answered: "if you think you wrote a wonderful text, throw it away, because it most certainly is not worth the trouble." The author itself is the worst reviewer of the scientific text. Therefore, before submitting the material for publication, the author should have it reviewed by people knowledgeable on research and the intricacies of the scientific text.
Clinical research in pediatric patients represents a separate area of research in human beings. In general, research involving children is allowed and supported by several laws, either ours or of other countries; however, one must take extra care. Many researchers who work with children forget to ask authorization to the child itself when it is already capable of understanding the work that will be done. This is delineated in every national and international standard. Those norms can be easily obtained on the address of the Conselho Nacional de Pesquisa (CNPq) on the Internet (www.cnpq.gov.br). Sometimes, referring to those norms avoids confusion, irritation, and loss of time resulting from the rejection of the work for publication. How many of our researchers are aware of the Nuremberg Declaration, Helsinki Declaration, and Resolution 196/96 of the Conselho Nacional de Saúde? What will be the reaction of an adjunct editor of a journal when, examining the methodology of the work finds out that many articles of those Conventions were not observed? How many national medical researchers follow the Medical Ethics Code when designing the study protocol?
Besides representing a special segment in every law and resolution, pediatric patients have special characteristics according to their age group. These characteristics include physiological and anatomical details that differ from that of adults, and developing systems that often times behave differently than those of adults. The data referring to the pharmacodynamics of anesthetic agents and adjuvant drugs are incomplete and they are almost non-existent when we treat children younger than one year old. This is partly due to ethical issues regarding research in pediatric patients, which forces us to extrapolate adult data to children. However, this is not always considered a proper conduct. In view of this fact, it is difficult to understand and accept that several drugs that were not submitted to adequate safety tests in adults that produce fleeting effects in the prolonged postoperative pain or are associated with clear and unacceptable side effects are still the focus of research in children. An unequivocal example is the use of neostigmine in the neuroaxis of pediatric patients. Some of those papers present a prevalence of nausea and vomiting greater than 30% in children submitted to this treatment. The conclusion of those authors is at best questionable: "Further studies should be conducted to confirm the use of neostigmine as spinal analgesic in clinical practice." If 30% of pediatric patients presented vomiting in the presence of neostigmine and this incidence is close to zero in the control groups, in which morphine or ketamine were used, I think there is little doubt that neostigmine should be used for what it has always been used: reversion of neuromuscular block. The information provided by works published could not be enough to justify the routine use of a certain drug or technique. The use of midazolam in the caudal space of children for the treatment of postoperative pain can be included in the example of neostigmine.
The size of the study population is a frequent problem among the works of our clinical anesthesiology researchers. The sample population should be validated when conclusions are based on statistics. The number of individuals in the study population, called "N" in the statistical jargon, should be validated. It is not just any group of 20 to 30 patients that will provide unquestionable results regarding an observed phenomenon. And the opposite is also true; 1,000 or 5,000 patients, which is frequently interpreted as a very important datum, do not make the study population reliable if the method is flawed. Authors who present such exuberant casuistic have great difficulty in accepting the rejection of their work or the criticism of more attentive readers. Besides, if we were to focus on the statistical methods used in thousands of published works, it would be possible to write a book on the mistakes made. Research methodology is learned at school. Without this training, the results will always be disastrous, and results and conclusions will be rejected by more demanding journals. The same is applied to the scientific work. It deserves a critical reading even after the editorial review, or if it were published in obscure journals. No one is authorized to apply in clinical practice, with children, information published without the proper screening. Brazilian and foreign authors frequently submit the same work to several journals until their work is finally accepted. Since there are hundreds of journals, those works will eventually be published. One should be aware that not every journal that publishes works in English has an Editorial Board, while others allow the "author" to chose the reviewer. If you are an author, avoid them. The aim of those journals is commercial, may it be by receiving financial support from the industry or selling signatures. We cannot include here the analysis of electronic journals, since the list is very extensive.
Novice authors, or arrogant ones, have the habit of emitting personal opinions about their results or conclusion, such as: "safe and effective method "; "in our experience, we observed that "; "our patients were thankful ". That is the reason for editorials and letters to the editor; they are the adequate forum for opinions, and not the pages of scientific articles or conclusions. This type of thing will be refused by editors and readers versed in scientific publications.
I close my comments with the teachings of Professor Gastão Fernandes Duval Neto, MD, in an editorial of the Revista Brasileira de Anestesiologia: "The educational and cultural behavior of future Brazilian anesthesiologists will improve the critical competence, both of the projects elaborated for scientific works and of new concepts of clinical practice preconized by the current literature."
José da Conceição
Member of the Editorial Board of the Revista Brasileira de Anestesiologia
Associated Editor Regional Anesthesia and Pain Medicine
Editorial Advisory Board Member Pediatric Anesthesia
01. D'Acampora AJ Investigação Experimental: do Planejamento à Redação Final. 1ª Ed, Florianópolis, Papa Livro Editora, 2001.
02. Camon VAA A Ética na Saúde. São Paulo, Pioneira, 1997.
03. Vasquez AS Ética. 19ª Ed, Rio de Janeiro, Civilização Brasileira, 1999.
04. Vieira SHWS Experimentação em Seres Humanos. São Paulo, Moderna, 1987.
05. Coucil for International Organizations of Medical Sciences International Ethical Guidelines for Biomedical Research Involving Subjects. Geneva, WHO, 1993.
06. Brasil. Ministério da Justiça. Conselho Nacional dos Direitos da Criança e do Adolescente (CONANDA) Resolução n° 041 de outubro de 1995. Direitos da criança e do adolescente hospitalizado.
07. Conselho Nacional de Saúde (Brasil) Resolução n° 251 de 05 de agosto de 1997. Diretrizes e normas regulamentadoras sobre pesquisa envolvendo seres humanos.
08. Conselho Nacional de Saúde (Brasil) Resolução n° 196 de 10 de outubro de 1996. Estabelece normas sobre pesquisas envolvendo seres humanos. Diário Oficial da União, Brasília, 16 out 1996:21082-21085.
09. Almenrader N, Passariello M, D'Amica G et al. Caudal additives for postoperative pain management in children: S(+)-ketamine and neostigmine. Pediatr Anesth, 2005;15:143-147.
10. Khan FA, Memon GA, Kamal RS Effect of route of buprenorphine on recovery and postoperative analgesic requirement in paediatric patients. Paediatr Anaesth, 2002;12:786-790.
11. Duval Neto GF Anestesiologia na era da medicina baseada em evidências. Rev Bras Anestesiol, 2004;54:141-144.