We are pleased to announce that the Editorial Committee of Rinsho Hyoka (Clinical Evaluation) has set to work to revise the Instruction for Authors which will start from this issue of the Journal. Further, in light of the recent world trend in evidence- based medicine (EBM) we shall use this opportunity to review the mission of the Journal within the context of this trend and to consider what is an ideal format for the publication of clinical trials.

　The publication of articles on pharmaceuticals especially those relating to clinical trials is undergoing drastic change. This situation require the establishment of an editorial policy that would allow the publication of quality, well-written, evidence-based articles which could be validly evaluated on a global perspective. The "Rinsho Hyoka" (Clinical Evaluation) cannot keep itself out of this trend.

　The Rinsho Hyoka started out as a voluntary study group around 1970 comprising of experts with strong interests in, and regards as crucial, the state of clinical trials in Japan. The group is composed of physicians and clinicians in various fields of medicine (e.g. psychiatrist, internist, ophthalmologist, gerontologist, gynecologist, etc.) as well as pharmacologist, lawyer, statistician and pharmacist. In its pursuit of ethically and scientifically-sound design and practice of clinical trials and of maintaining fairness and reliability of results of such trials, the study group, in 1972, established the "Rinsho Hyoka" to enable its members to organize their activities and to practice their ideals with strong sense of duties and to provide a forum for the publication of clinical trial results.

　Since the establishment of the Journal, we have published not only results of clinical trials but also various articles on issues relating to methodology, statistics, ethics, legislation and domestic and foreign guidelines relating to or affecting clinical trials. We also endeavored to promote the double-blinding method which is now widely known and practiced in Japan. Efforts were focused on the publication of negative trials, reports on adverse reactions and articles pertaining to ethical problems which inevitably arise during the treatment period under probabilistic expectation or problems of significance and limitation in various methods of statistical tests analyses where the objects of study are human beings. This is a very unique and important editorial policy. We exerted efforts to publish trials even if the results are negative (i.e., no findings could be obtained as to the drug's efficacy or the investigation was terminated due to safety problems). Through these efforts, our Journal has been regarded as a pioneer in the publication of articles in the general fields of clinical study in Japan.

　We have established and maintained close relationships with specialists and experts in Europe and the United States particularly with the staff of the U.S. Food and Drug Administration who have been very helpful in providing information to answer our questions enabling us to comprehend their current situation. We have conveyed these information to the public through the Journal and through communications with the Ministry of Health and Welfare. We believe that these efforts resulted in the improvement of the quality of clinical trials in Japan putting it at par with international standards.

　The rapid technological advancement in the fields of science especially the development of electronic media as a communication tool necessitates a demand for global reconstruction and coordination. This holds true also in the area of drug investigation. The ICH (International Conference on Harmonization of Technical Requirements for the Registration of Pharmaceuticals for Human Use) movement provided the forum to promote global coordination in this area through the standardization of each country's regulations pertaining to the registration and approval of pharmaceuticals with a view to avoiding the useless duplication of clinical trials during the new drug approval process thereby facilitating the approval and registration of new drugs. Accordingly, there is now a pressing need to improve the quality of clinical trials conducted in Japan as well as in the publication of such trials based on scientifically-sound judgments to meet international standards.

　Evidence-based medicine has become a world trend since the second half of 1990s. David L.Sackett and colleagues, in 1996, gave a more concrete definition that EBM is "the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients". The current best evidence can be obtained through critical appraisal and systematic research now made more fast and accurate by the development in computer science and information technology. This best external evidence is integrated with individual clinical expertise as well as the quality of health facilities and patients' value system and preference so as to suit actual circumstances and meet patient real need. In this context, a drastic reformation in the publication of clinical studies and medical literatures have become a required undertaking.

　The "ACP Journal Club" and the "Evidence-Based Medicine" are examples of undertakings following this trend. These are secondary information journals which select from biomedical literatures original and scientifically reliable articles and reviews on clinical trials. These articles are then summarized in value-added abstracts and commented on by clinical experts. Another example is the "Study Project for Educating Research Librarians to Support EBM" sponsored by the Japanese Ministry of Health and Welfare and spearheaded by Dr. Hiroshi Nakajima, Director of the International Research Institute of Health and Welfare. The aim of this study project is to train research librarians as medical information specialists in the collection, selection and organization of medical information and articles from electronic databases journal, literatures and abstracts, summarizing and disseminating these information in a timely fashion to alert clinicians and health practitioners on important advances in medicine.

　Archiebald Cochrane (1909-1988),who was a British physician-epidemiologist, once stated that -- "It is surely a great criticism of our profession that we have not organized a critical summary, by specialty or sub-specialty, updated periodically, of all relevant randomized controlled trials." His dream came to be true in the form of the CDSR (Cochrane Databases of Systematic Reviews) which is provided in "The Cochrane Library" CD-ROM , as well as through the website. The CDSR initially covered limited topics but is gradually expanding to cover more and more topics. It is highly expected that it will play an important role in the promotion of EBM in the future.

　The criterion in selecting articles under EBM is based on the levels of the evidence which are ranked according to study design. These are: meta-analysis > RCT (randomized controlled trial) > CCT (controlled clinical trial) > cohort study > case-control study > case series > case report. In 1993, the AHCPR (Agency for Health Care Policy and Research) in the U.S. provided a grading scale which is also based on the same concept. Therefore, from the EBM standpoint, evidences derived from meta-analysis or RCTs are regarded to be the most reliable.

　In light of these developments and to keep pace with international trends particularly with regard to the EBM as described above, we are accordingly revising our publication guidelines as follows:

1) Adoption of the format of describing reference listing from the URM (Uniform Requirement for Manuscripts Submitted to Biomedical Journal) (also called the Vancouver-style). The URM formulates the criteria/guidelines for submission of manuscripts and articles. It was established by a group of editors of medical journals during their meeting in 1978 in Vancouver, British Columbia. The group became known as the Vancouver Group, and they evolved into the ICMJE (International Committee of Medical Journal Editor) which meets annually to review and update the URM guidelines. The ICMJE published the fifth edition of the URH in 1997.

2) Adoption of the CONSORT (Consolidated Standards for Reporting Trials) which was an undertaking resulting from meetings which comprised various working groups (i.e. SORT Working Group, Asilomar Working Group, etc.) to sort out problems and improve the quality of reporting of randomized controlled trials (RCTs). Referred to as the "CONSORT Statement", it was published as a Special Communication in the August 28, 1996 issue of the JAMA (Journal of the American Medical Association) and other international journals. The CONSORT encourages the structured reporting of RCTs and provides standards so that these reports are able to convey to the reader relevant information concerning the design, conduct, analysis and generalizability of the trial. The thorough evaluation of these reports can have a powerful and immediate impact on health and medical care. Therefore, the information included therein should provide the reader with the ability to make informed judgments regarding the internal and external validity of the trial.

The CONSORT provides a checklist of 21 items and flow diagram to be used in reporting of clinical trials. While an optimally reported trial will address the items on the checklist, these important items can essentially be summarized and introduced according to the following headings:

a) Title: The title should be concise and informative (i.e. clearly identifying the trial as an RCT)
b) Abstract: Use a structured format
c) Introduction: State the objectives of the study. Summarize the rationale for the study or observation. State prospectively defined hypotheses
d) Method: Describe all major elements of the study (i.e. protocol, assignment, methods of masking (blinding). Identify all methods and procedures used in sufficient detail.
e) Results: Provide a trial profile summarizing participant flow, follow-up and analysis.
f) Comments: State specific interpretation of study findings and general interpretations of the data in light of the totality of the available evidence.

3) Require the submission of structured abstracts not only for reports on RCTs as described in the second item above but also for other original articles and reviews. Abstracts and citations of RCTs are now being processed in the Medline, EMBASE and in the CENTRAL /CCTR (Cochrane Controlled Trials Register), a sub-project of the Cochrane Library which processes all RCTs submitted from around the world. Furthermore, RCTs are systematically examined and reviewed through the Cochrane Collaboration. The results of the meta-analysis are integrated into the CDSR and then disseminated to clinicians around the world thereby contributing to the practice of EBM worldwide. Therefore, structured abstracts will provide essential benefits to clinicians and researchers around the world since these abstracts can directly provide information on high quality RCTs that are useful to them and can be easily scanned or searched through various kinds of electronic databases.

　We are pleased to inform that the abstracts and citations of RCTs published in the Rinsho Hyoka are now in the process of being integrated into the CENTRAL/CCTR (Cochrane Controlled Trials Register).

4) Acceptance of submissions from the public. Though not exactly described in our former instruction for authors, in the past years, we only accept and publish articles or reports of RCTs on which we can provide quality assurance based on the participation of our members in such trials. Our quality assurance, therefore, on the scientific and ethical validity and reliability of the trial is based not only on the review of literatures but also on the actual experience of our members. But from now on, we will accept submissions of high quality clinical reports or articles locally or abroad.

　We are providing with this issue the preliminary guidelines, referred to as "Instruction for Authors", for the submission of manuscripts and articles.

　The Ministry of Health and Welfare (Koseisho) in its announcements under PAB (Pharmaceutical Affairs Bureau) Notification No. 481 and PAB Notification No. 666 (both dated April 8, 1999) provides among others the requirements for submission of new drug applications and items to be submitted in support of such applications. Koseisho, in its attempt to expedite new drug approval process, have deregulated industrial activities by expanding flexibility in the management and approval of new drug applications based on scientific rationality without sacrificing quality, efficacy and safety of drugs products. Under this scenario, a major change in the new drug approval process was made, that is, the abolishment of the publication requirement for clinical trials.

　On the other hand, Koseisho announced that all "Shinsa Shiryou Gaiyo" (Approval Summary) and documents relating to the process evaluation should be integrated into the "Shinyaku Shonin Shiryoushu" (NDA Approval Information Catalogue) which would be opened to the public through the internet.

　About 2,500 medical journals are published in Japan, 300 of which are included either in the Medline or EMBASE. However, since it is difficult for foreigners to access and read articles written in Japanese, only a small portion of Japanese RCTs can be referred to internationally. Because of this language barrier, results of clinical studies conducted in Japan are seldom utilized in global systematic reviews like those carried out by the Cochrane Collaboration. This situation results in a publication bias and significantly gives rise to the problem of promoting EBM on a global perspective.

　At the moment, it is not clear how Koseisho can integrate the information on new drug applications into international databases such as Medline, EMBASE and CENTRAL in the future.

　We are inevitably faced with various kinds of problems in the field of clinical practice, but we are trying our best to develop and promote EBM in Japan through the establishment of infrastructures and up-to-date editorial policy for the publication and dissemination of important articles on clinical trials. This is the primary mission of Rinsho Hyoka.

　We will endeavor to develop our communication technology and editorial expertise so that information on Japanese clinical studies are constructed within a global perspective and distributed in such a way that it will reach those who need them. Our Journal has been regarded as one of the major journals contributing to the improvement of medical science and treatment in Japan. We will continue to provide our readers with various kinds of evidence-based information that will help them in their decision-making and clinical practice.

　In Japan, it is the duty of the chief investigator to voluntarily publish worldwide the results of clinical trials to the extent that such publication will not violate or conflict with the intellectual proprietary rights of the sponsor-company. This is primarily done as an expression of appreciation to the patients and who participated participants in the trial.

　In the past years, our Journal only published results of clinical studies where some of our editorial staff participated in as members of the "Controller Committee" (an affiliate of Rinsho Hyoka). In line with the preliminary revision of the Instruction for Authors, we will accept articles from the public only if these articles will contribute to the promotion of EBM. This means that we will welcome articles which can provide useful information in the field of clinical trials. For example, those articles which "Tsukuru" (generate) evidence or information in the field of clinical practice which "Tsukau"(use) evidence, or information in the field of information sciences which "Tsutaeru"(distribute) the evidence.

　Additionally, it will be possible for us to take up the role of providing communication network linking the Institutional Review Boards (IRBs) all over the country for the promotion of proper and valid clinical trials.

　With the revision of the Japanese Good Clinical Practice and the Guideline of Statistics in line with the ICH agreements, we believe that the development in our editorial policy, which recognizes the significance of disseminating evidences and information acquired from high quality clinical trials, will contribute to the attainment of the goal of spreading the concept of rational drug use. In the spirit of this principle, we wish to create fresh features so as to make reading our Journal pleasant and comprehensible for a wide range of readers.

September, 1999.

The Editorial Board of Rinsho Hyoka (Clinical Evaluation)
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