A Survey of Clinical Trials of Antibiotic Prophylaxis in Colon Surgery: Evidence against Further Use of No-Treatment Controls

To evaluate the use of antibiotics given prophylactically in colon surgery, we examined 26 trials published from 1965 to 1980 in which patients given various antibiotic regimens were compared with controls given no antibiotic treatment. In 22 (85 per cent of these trials) antibiotics reduced postoperative wound infection (P<0.05 in 14). Combining the results of the trials published from 1965 to 1975 reveals a 95 per cent confidence interval for the true difference in infection rates of 14±6 per cent (36 per cent for control group vs. 22 per cent for treatment group) and the true difference in death rates of 6.7±4.4 per cent (11.2 per cent for control group vs. 4.5 per cent for treatment group). Yet trials employing control groups given no treatment continue to be reported. Since the use of such controls is justified only when no effective alternative therapy exists, we believe that any further trials of antibiotic prophylaxis in colon surgery should employ a previously proved standard. However, steadily increasing efficacy of treatment means that comparisons of new therapies with standard therapies will become prohibitively expensive because of the large number of patients required. (N Engl J Med. 1981; 305:795–9.) THE use of prophylactic antibiotics in colon surgery has been the topic of at least 50 randomized controlled trials in the last 16 years. As a result, the subject has become an apt one for the construction of peer-review guidelines.¹ Several detailed reviews of the subject have discussed the relative merits of various antibiotic regimens.^{2 3 4 5} Our study began as an investigation of the quality of the trials evaluating antibiotics, but this report concerns both the continuing use of no-treatment control groups in the trials and the possibility that accumulating evidence of drug efficacy has not received sufficient attention from all.