TY - JOUR
T1 - Confronting the issues of patient safety and investigator conflict of interest in an international clinical trial of myocardial reperfusion
AU - Topol, Eric J.
AU - Armstrong, Paul
AU - Van de Werf, Frans
AU - Kleiman, Neal
AU - Lee, Kerry
AU - Morris, Douglas
AU - Simoons, Maarten
AU - Barbash, Gabriel
AU - White, Harvey
AU - Califf, Robert M.
AU - Global Utilization of Streptokinase, Utilization of Streptokinase
N1 - Funding Information:
Disclosure to ACC If >30(i No Dsclosure with publication Doslos a with lectures Disclosure if invited speaker. Comminee -Proposed guidelines September 1989. BARI = Bypass Angioplasry Revascularization Investigation : CABO = coronary artery bypass grant GUSTO = Global Utilisation of Sueptokinase and n-PA for Occluded Coronary Aoeries NIHIADAMHA = National Institutes of Health and Alcohol . Drug Abuse, and Mental Health Administration; No = not permitted; ref. = reference : TIMI = Thrombolysis in Myocardial Infarction .
Funding Information:
be no remuneration for a consultancy arrangement, expertise or service during the course of the trial. Such guidelines apply not only to the investigator but to his or her spouse, dependents and family . This "freedom from equity or employment" rule, adopted by several designers of clinical trials and organizations suet, as the American Medical Association (10) and the American Federation for Clinical Research and institutions such as Harvard Medical School (9). appears to represent an emerging consensus . There is continued debate, however, exemplified by the subsequent rejection as draconian of the draft guidelines from September 1989 of the National Institutes of Health and the Alcohol . Drug Abuse and Mental Health Administration (21-25) . On the other hand, the limitations of simple disclosure are well recognized (26) . The GUSTO Steering Committee decided to significantly extend the standard criteria. By unanimous vote, it banned honoraria paid by the trial sponsors for educational activities or lectures and reimbursement for travel expenses. Investigator travel related to the research project is being reimbursed from the study's budget. In recognition of the critical time period after completion of the trial and dissemination of the data . along with the possibility that any financial ties during the phase of presentation of data might delicately affect the tone or interpretation of a lecture, the Steering Committee also extended the period for avoidance of any financial ties to I year after formal publication of the trial's primary results . In contrast, many other trials either have not specified the duration of potential conflict of interest or have ceased applying guidelines as soon as the data have been publicized (Table 2). The guidelines are applicable to all of the sponso s, which in this trial include Bayer (New York, New York) ; CIBA-Corning Diagnostics (Medfield, Massachusetts) ; Genentech (South San Francisco. California); ICI Pharmaceuticals (Wilmington, Delaware) and Sonofi Pharmaceuticals (Paris, France) . In addition, these safeguards were adopted by the Steering Committee and the Data Safety and Monitoring Committee and all members of the Data Coordinating Center. At the level of participating site principal investigators, written documentation is required that acknowledges the lack of any equity interest in the sponsors . We believe that such stringent guidelines, albeit not absolutely necessary, are important to ensure the highest level of integrity for the project throughout its execution and dissemination phases.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 1992/5
Y1 - 1992/5
N2 - The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial is a large scale international trial of new myocardial reperfusion strategies. The primary hypothesis is that early and sustained coronary artery recanalization will be associated with a significant reduction in mortality. The four regimens that are being tested are 1) streptokinase with subcutaneous heparin; 2) streptokinase with intravenous heparin; 3) accelerated recombinant tissue-type plasminogen activator (rt-PA) with intravenous heparin; and 4) combination streptokinase, rt-PA and intravenous heparin. The planned recruitment of 41,600 patients in 1,500 sites from 15 countries is expected to be completed by December 1992 and will enable detection of a 15% reduction or 1% absolute difference in mortality compared with that associated with standard therapy (streptokinase and subcutaneous heparin). In designing the trial, two important issues were directly addressed. First, a strategy was developed to provide assurance of patient safety during large scale investigational use of an aggressive thrombolytic regimen. This includes fascimile transmission of a one-page safety summary form to the Data Coordinating Center within 24 h of death or discharge, acceptance of the concept of "net clinical benefit" and close surveillance of the trial's progress by the independent Data and Safety Monitoring Committee. Second, to avoid potential conflict of interest beyond elimination of any position of financial equity, the Steering Committee unanimously voted to prohibit any honoraria for speaking engagements, payment for consultancy or travel or reimbursement of any kind from any of the five corporate sponsors until 1 year after publication of the results. Incorporation of these approaches may facilitate the design of future large scale randomized trials in cardiovascular medicine.
AB - The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial is a large scale international trial of new myocardial reperfusion strategies. The primary hypothesis is that early and sustained coronary artery recanalization will be associated with a significant reduction in mortality. The four regimens that are being tested are 1) streptokinase with subcutaneous heparin; 2) streptokinase with intravenous heparin; 3) accelerated recombinant tissue-type plasminogen activator (rt-PA) with intravenous heparin; and 4) combination streptokinase, rt-PA and intravenous heparin. The planned recruitment of 41,600 patients in 1,500 sites from 15 countries is expected to be completed by December 1992 and will enable detection of a 15% reduction or 1% absolute difference in mortality compared with that associated with standard therapy (streptokinase and subcutaneous heparin). In designing the trial, two important issues were directly addressed. First, a strategy was developed to provide assurance of patient safety during large scale investigational use of an aggressive thrombolytic regimen. This includes fascimile transmission of a one-page safety summary form to the Data Coordinating Center within 24 h of death or discharge, acceptance of the concept of "net clinical benefit" and close surveillance of the trial's progress by the independent Data and Safety Monitoring Committee. Second, to avoid potential conflict of interest beyond elimination of any position of financial equity, the Steering Committee unanimously voted to prohibit any honoraria for speaking engagements, payment for consultancy or travel or reimbursement of any kind from any of the five corporate sponsors until 1 year after publication of the results. Incorporation of these approaches may facilitate the design of future large scale randomized trials in cardiovascular medicine.
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M3 - Article
C2 - 1564212
AN - SCOPUS:0026521772
VL - 19
SP - 1123
EP - 1128
JO - Journal of the American College of Cardiology.
JF - Journal of the American College of Cardiology.
SN - 0735-1097
IS - 6
ER -