682 Abs~a~s

Clinical data are at the core of both remote data entry applications and electronic medical record appli- cations. Nevertheless both worlds do not communicate well technically and methodologically.

We have developed MEDAR, a clinical applications generator which is used to create both remote data entry applications and electronic medical record applications. Data entry for the clinical trial can be integrated within the daily routine of clinical practice. This has many advantages other than those of remote data entry:

1. OptimalizaUon of patient recruitment • each collaborating site's clinical database can be searched with the inclusion and exclusion criteria to

estimate each site's expected recruitment rate based on exact numbers from past clinical practice. • each patient whose clinical data from the practice database match the criteria can be solicited actively

to participate in the study. • Ineligible patients will be excluded before active medication is started.

2. Integration of data entry for clinical trials in the automated medical record is the sole guarantee for data completeness and data validity, since data validation is done automatically for the own medical record (source data equal study data).

P39 MANAGEMENT OF STUDY PROPOSALS: FROM AN IDEA TO A MANUSCRIPT

Sandra Forman and Peggy Noble for the TIMI Investigators

Maryland Medical Research Institute Baltimore, Maryland

Large multicenter studies collect data to answer the scientific question for which the study was designed. In the process a large amount of additional data are collected, investigators in multicenter studies are encouraged to submit proposals for further analysis of the database.

The Thrombolysis in Myocardial Infarction (TIMI) Tdal is a NHLBI supported multicenter randomized trial designed to determine whether intravenous thrombolytic therapy given in the early hours of myocardial infarction should be followed by percutanecus transluminal coronary angioplasty. In TIMI, three types of analysis proposals were identified: end-point studies, data bank studies and ancillary studies.

The final goal is a presentation at a scientific meeting and eventually a manuscript. A review procedure at each step: proposal, analysis request, abstract, presentation, and manuscript, is important to protect the integrity and scientific merit of the entire study. These procedures are intended to protect the interests of all participants in the trial, namely, to assure that study data conform to the requirements of study design, are accurately presented, authorship is appropriately acknowledged, and the text of all publications is well written.

Since the beginning of TIMI in 1984, there have been 106 presentations and 45 publications. This pre- sentation will describe the steps from proposal receipt at the Coordinating Center to manuscript publication.

P40 IMPLEMENTING THE EUROPEAN COMMUNITY (EC) GOOD CLINICAL PRACTICE GUIDELINES IN

CANADA: A NATIONAL COOPERATIVE GROUP'S REPORT

Nancy Paul National Cancer Institute of Canada

Queen's University Kingston, Ontario, Canada

The guidelines "Good Clinical Practice for Trials on Medicinal Products in the European Community" (GCPT) are due to come into operation July 1, 1991. The impact of the GCPT will be felt worldwide. The NCIC CTG coordinates large multicenter clinical trials in cancer therapy in Canada and internationally, and is the only such group in Canada with a national base. In an effort to promote global consistency of standards and ensure its own compliance to them, the NCIC CTG has set out to incorporate the GCPT into its own standard operating procedures (SOP).

The five sections of the GCPT--(1 ) Protection of Trials Subjects and Consultation of Ethics Committees, (2) Responsibilities, (3) Data Handling, (4) Statistics, and (5) Quality Assurance---will be reviewed early in 1991 point by point and compared with current NCIC CTG policies and practice. It is anticipated that the exercise will prove extremely valuable. Most importantly, it will provoke a thorough self-examination. Existing requirements will be questioned; ideas for improvement will be generated and discussed. A reconsideration of fundamentals may reveal activities carried out through habit or mistaken assumption. Certainly, an intensive comparative review of the GCPT with our own SOP could help clarify our interaction with the Canadian

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regulatory authority (the Health Protection Branch of the Federal Government) as well as with authorities in the United States and of course Europe--not to mention the multinational pharmaceutical companies with which we often share study coordination.

The self-evaluative process, highlights of the resulting critique, and plans for corrective or affirmative initiatives will be presented.

P41 CONDUCTING CLINICAL STUDY OF GCP STANDARDS IN THE SOVIET UNION-CASE ANALYSIS

J. Vuorlnen, A. HaJbe and H. Kiipyllt Orion Corporation Farmos

Turku, Finland

A phase III clinical study on a novel antiestrogenic agent, Toremifene, aimed to be pivotal documentation for international registration purposes, is in progress in the Soviet Union.

In order to meet all the requirements of a GCP (Good Clinical trial Practise) standards many aspects had to be taken into account, among others: questions of the national legislation, level of the general health care system, ethical questions, attitudes of the patients and the investigators, conceptual differences and practical preconditions.

After a successful run-in period the main study proceeds according to the requirements of the protocol, full fulling all GCP regulations. At the time being the half time interim report is under preparation.

Ethical, regulatory and practical aspects due to the extraordinary conditions, as well as some statistical considerations will be discussed.

P42 A FUNDING MECHANISM FOR CLINICAL TRIALS: THE CLINICAL TRIAL PLANNING GRANT

Natalie KurlnlJ, Richard L. Mowery and Donald F. Everett National Eye Institute Bethasda, Maryland

The Clinical Tdal Planning Grant (CTPG) was created by the National Eye Institute (NEI) to assist inves- tigators in preparing clinical tdal applications for peer review. The CTPG provides one year of funding support ($50,000 direct costs) and has two pdmary advantages: (1) provides early peer review of the rationale for the trial; and (2) supports development of the Manual of Procedures (MOP). The CTPG also enables inves- tigators to form planning committees, conduct feasibility studies, and document recruitment. Investigator- initiated NEI clinical trial applications require a detailed MOP. Preparation of the MOP is both timeconsuming and costly particularly when the trial concept has not been peerreviewed. The CTPG provides early peer review of the trial rationale, exporimental design, planned procedures and analyses, and recruitment potential. Since inception of the CTPG in mid-1989, the NEI has received and peer-reviewed five applications. The funding rate is 80% indicating high enthusiasm for the CTPG by peer-reviewers and the National Advisory Eye Council. Both U.S. and foreign investigators may apply for this grant. Application procedures, the review process, and the advantages and disadvantages of the CTPG will be presented.

P43 USE OF INTERIM ANALYSES TO DESIGN FURTHER STUDIES IN DRUG PROGRAMS

Katherine Llpachullz, Albert Getaon, Robert Davis and Balasamy ThlyagaraJan Merck and Company

Blue Bell, Pennsylvania

Interim analyses are most often implemented as ethical safety nets for large mortality trials. Interim analyses can also be useful in the development of a broad range of drugs where the assessment of efficacy involves end-points other than mortality. This paper describes a situation in which the clinical development of a new analgesic compound was initiated with a large full scale trial efficacy trial instead of a smaller pilot study. An intedm assessment of the pivotal study was planned to confirm the efficacy results predicted by pharmaco- kinetic studies and to identify appropdate doses to be used in subsequent trials. Thus when the feasibility of the program was supported by the intedm assessment, one of the required well-controlled tdals was already underway. Instead of formal hypothesis testing, the intedm look consisted of summary statistics and an assessment of the probability that the tdal would yield appropriate significant results at its conclusion.