Randomized clinical trials in surgery.

When it is well conducted, a randomized clinical trial provides the strongest evidence available for evaluating the comparative effectiveness of the interventions tested. Over the last two generations, we have learned much about various devices for strengthening them and about methods of avoiding pitfalls in their design, execution, analysis, and reporting. In a trial, we seek evidence for a causal link between treatments and observed outcomes. Because the controlled trial depends on an argument based on exclusion (i.e., no other causes or differences affected the experimental groups), we strengthen its inference by taking steps to exclude any such differences. This article discusses a number of issues that deserve consideration: problems and generalizability, devices for strengthening trials, issues of power and sample size, the relationship between study design and reported gains, when to undertake a trial, the role of collaborative trials, and ways to make trials more feasible in clinical settings.

Quality of life variables in surgical trials.

Clinical trials are commonly performed in surgery to assess the efficacy of one or more treatments. Many therapies result in only partial or temporary improvement, rather than cure. Others sharply affect the quality of patients' lives or of their deaths. For most interventions, it is important to document effects on quality of life as well as morbidity and mortality rates. yet, a review of the literature reveals that very few surgical trials consider quality of life variables as outcome measures. Surgical investigators in areas like cancer, inflammatory bowel disease, end stage renal disease, and cardiac disease have examined quality of life issues extensively using a variety of scales and indices. However, most studies on quality of life are hampered by poor design and inadequate methods of assessment. Failure to evaluate quality of life variables prevents the recognition and full use of potentially beneficial therapies and the rejection of potentially harmful ones.

Reporting clinical trials in general surgical journals.

Readers need information about the design and analysis of a clinical trial to evaluate and interpret its findings. We reviewed 84 therapeutic trials appearing in six general surgical journals from July 1981 through June 1982 and assessed the reporting of 11 important aspects of design and analysis. Overall, 59% of the 11 items were clearly reported, 5% were ambiguously discussed, and 36% were not reported. The frequency of reporting in general surgical journals is thus similar to the 56% found by others for four general medical journals. Reporting was best for random allocation (89%), loss to follow-up (86%), and statistical analyses (85%). Reporting was most deficient for the method used to generate the treatment assignment (27%) and for the power of the investigation to detect treatment differences (5%). We recommend that clinical journals provide a list of important items to be included in reports on clinical trials.

Reporting on methods in clinical trials.

A clinical trial cannot be adequately interpreted without information about the methods used in the design of the study and the analysis of the results. To determine the frequency of reporting what we consider 11 important aspects of design and analysis, we surveyed all 67 clinical trials published in the New England Journal of Medicine, the Lancet, and the British Medical Journal from July through December 1979 and in the Journal of the American Medical Association from July 1979 through June 1980. Of all 11 items in the 67 trials published in all four journals, 56 per cent were clearly reported, 10 per cent were ambiguously mentioned, and 34 per cent were not reported at all. At least 80 per cent of the 67 trials reported information about statistical analyses, statistical methods used, and random allocation of subjects, yet only 19 per cent reported the method of randomization. Loss to follow-up was discussed in 79 per cent of the articles, treatment complications in 64 per cent, and admission of subjects before allocation in 57 per cent, but eligibility criteria for admission to the trial appeared in only 37 per cent. Although information about whether patients were blind to treatment was given in 55 per cent, information about whether there was blind assessment of outcome was reported in only 30 per cent. The statistical power of the trial to detect treatment effects was discussed in only 12 per cent of the articles. The clinical trials published in The New England Journal of Medicine reported 71 per cent of the 11 items, those in the Journal of the American Medical Association 63 per cent, those in the British Medical Journal 52 per cent, and those in the Lancet 46 per cent. These rates are significantly different (P less than 0.001). We recommend that editors improve the reporting of clinical trials by giving authors a list of the important items to be reported.

Preventable anesthesia mishaps: a study of human factors.

A modified critical-incident analysis technique was used in a retrospective examination of the characteristics of human error and equipment failure in anesthetic practice. The objective was to uncover patterns of frequently occurring incidents that are in need of careful prospective investigation. Forty-seven interviews were conducted with staff and resident anesthesiologists at one urban teaching institution, and descriptions of 359 preventable incidents were obtained. Twenty-three categories of details from these descriptions were subjected to computer-aided analysis for trends and patterns. Most of the preventable incidents involved human error (82 per cent), with breathing-circuit disconnections, inadvertent changes in gas flow, and drug-syringe errors being frequent problems. Overt equipment failures constituted only 14 per cent of the total number of preventable incidents, but equipment design was indictable in many categories of human error, as were inadequate experience and insufficient familiarity with equipment or with the specific surgical procedure. Other factors frequently associated with incidents were inadequate communication among personnel, haste or lack of precaution, and distraction. Results from multi-hospital studies based on the methodology developed could be used for more objective determination of priorities and planning of specific investments for decreasing the risk associated with anesthesia.

PIP: This study attempted to quantitate anesthesia mishaps related to human error rather than to operative procedures, the patient's disease, age, physical status, or other factors. This risk study collected information by interview with staff and residient anesthesiologists in a large metropolitan teaching hospital. The analysis technique, called critical-incident, was used to determine patterns of frequently occurring incidents leading to anesthetic failure or patient injury. 47 interviews were conducted, and 359 preventable accidents were described. There were 23 categories of details gleaned from these descriptive interviews which were computer analyzed for trends and patterns. The incidents ranged in seriousness from laryngoscope malfunctions to breathing-circuit disconnections resulting in death. Human error was involved in 82% of preventable accidents, and equipment failure accounted for 14%. The remaining 16 incidents did not fall in either category. The 10 most frequently occurring incidents (human error and equipment failure combined) were: 1) breathing circuit disconnection; 2) inadvertent gas flow change; 3) syringe swap; 4) gas supply problem; 5) intravenous apparatus disconnection; 6) laryngoscope malfunction; 7) premature extubation; 8) breathing circuit connection error; 9) hypovolemia; and 10) tracheal airway device position changes.

Development of two indices of postoperative morbidity.

Two indices of postoperative morbidity, Nursing Assessment Index and Observed Treatment Index, are described and evaluated in this study of 4,182 consecutive anesthetics. The use of these indices in studies of the quality and effectiveness of surgical and anesthetic care should increase the economy and precision with which the causes of unsatisfactory outcome are identified. Specific illustrations of the relationship of the preanesthetic status of patients to their postoperative morbidity as measured by these indices and mortality rates are given. In addition these two indices of morbidity measured on the seventh postoperative day are shown to be strongly co-related with subsequent in-hospital deaths. Thus, of the 100 patients with a Nursing Assessment Index worse than 3, 19 percent died; only 0.4 percent of the 550 patients who had no morbidity as measured by this index died. Although they ultimately survive, about an equal number of patients become seriously ill as die follow operations.

Onset of postoperative jaundice related to anaesthetic history.

A review of 182 cases from the U.S. National Halothane Study showed the interval to the onset of jaundice after one exposure to halothane (91 cases) to be slightly shorter than the interval for those having had multiple exposures to the agent. These findings are in sharp contrast to other recently published results. Thirty-three cases of jaundice after the use of other anaesthetic agents are also reported.