PHASE-IV STUDY OF PROPOFOL - VALIDATION OF THE DATA SET

In 1989-1990, Stuart Pharmaceuticals conducted a Phase IV study of pro pofol on over 26,000 patients, later making the large data base availa ble to a team of epidemiologists and anesthesiologists for analysis. W e now describe the process of verifying the data to provide a sound ba sis for further analyses. Original data were collected by 1819 physici ans at 1761 hospitals. In that study, anesthesia was induced by bolus injection of propofol and was maintained by inhaled drug and N2O-O2 (S tep 1), or by propofol (either intermittent bolus injection [Step 2] o r continuous infusion [Step 3]) and N2O-O2. Forty-six recorded variabl es described history, physical examination, course and quality of anes thesia and recovery, and adverse events. Data were scrutinized for ina ccuracy or bias regarding adverse events, completeness of data, data e ntry, and violations of the study protocol. The initial data set perta ined to 26,841 patients (10,698, Step 1; 8886, Step 2; and 7257, Step 3). Because we excluded data if 25% of the items were missing from the data set, 3.2% of the case reports were eliminated: the final data se t used for subsequent analyses contained 25,981 patients (10,184, Step 1; 8672, Step 2; and 7125, Step 3). Inaccuracy of data entry was not excessive, and violations of study protocol were less frequent than in similar studies. The nature and frequency of adverse events were simi lar to those reported in Phase II and III clinical trials of propofol. Analysis showed that missing data occurred randomly and did not intro duce obvious bias. We conclude that the data set was valid and most li kely represents perioperative events occurring in similar patients; th at Phase IV studies can be valuable because of the range of patients s tudied and the ability to detect even rare events; and that future Pha se IV studies could be improved by more efficient design of data colle ction forms for both hypotheses to be tested and the entry of data ont o forms.