The retrieval of randomized clinical trials in liver disease from the medical literature. A comparison of MEDLARS and manual methods. National Cooperative Crohn's Disease Study: results of drug treatment. Omega-3 free fatty acids for the maintenance of remission in Crohn disease: the EPIC Randomized Controlled Trials.
Randomized clinical trials (RCTs) provide the most reliable therapeutic information available. Unfortunately, there are no systemic listing of RCTs. We compared a MEDLARS search of 3686 biomedical journals for RCTs with a manual search of the medical literature for the period 1966-1982. For the former search we used subject headings (1) liver disease or (2) biliary tract disease and subheadings (1) drug therapy, (2) surgery, (3) radiotherapy, or (4) therapy, and check tags (1) comparative study or (2) clinical research. For the manual search, the contents of 34 arbitrarily selected, gastroenterologic, hepatologic, surgical, or general journals were perused. The MEDLARS search identified 160 RCTs and 29 others were found in the references of the 160. One hundred fifty-four RCTs were identified by both methods. The manual search identified 208 RCTs and an additional 34 were found in the references of the 208. The MEDLARS search identified only 107 of 208 RCTs found in the references of the 208. The MEDLARS search identified only 107 of 208 RCTs found manually in the 36 journals, an efficiency rate of 51%. We estimate that 330 hepatobiliary RCTs had been published during this 17-year period. Sixty percent of the RCTs found by MEDLARS used the key word "randomized," "double blind," or "controlled" in the title, compared to 36% in those found by the manual search. In order to retrieve RCTs, it is essential that editors require that RCTs be identified in their titles or key words by specific terms such as "controlled," "randomized," and "double blind," that papers be so catalogued and indexed, and that searchers be instructed in appropriate search strategies. The response of active and quiescent Crohn's disease to prednisone, sulfasalazine, or azathioprine has been studied in 569 patients in a placebo-controlled, randomized, multicenter cooperative trial. The response of active symptomatic disease to prednisone or sulfasalazine was significantly better than to placebo. Response to azathioprine was better than to placebo, but the difference did not reach conventional levels of statistical significance. Patients with colonic involvement were especially responsive to sulfasalazine, and those with small bowel involvement were especially responsive to prednisone. Patients' drug therapy immediately before entry to the study significantly affected subsequent response. For patients with quiescent disease, none of the drugs was superior to placebo in prophylaxis against flare-up or recurrence. There is less than a 5% risk that a clinically significant prophylactic effect of any of the drug regimens was missed. Maintenance therapy for Crohn disease features the use of immunosuppressive drugs, which are associated with an increased risk of infection. Identification of safe and effective maintenance strategies is a priority.
                To determine whether the oral administration of omega-3 free fatty acids is more effective than placebo for prevention of relapse of Crohn disease.
                Two randomized, double-blind, placebo-controlled studies (Epanova Program in Crohn's Study 1 [EPIC-1] and EPIC-2) conducted between January 2003 and February 2007 at 98 centers in Canada, Europe, Israel, and the United States. Data from 363 and 375 patients with quiescent Crohn disease were evaluated in EPIC-1 and EPIC-2, respectively.
                Patients with a Crohn's Disease Activity Index (CDAI) score of less than 150 were randomly assigned to receive either 4 g/d of omega-3 free fatty acids or placebo for up to 58 weeks. No other treatments for Crohn disease were permitted.
                Clinical relapse, as defined by a CDAI score of 150 points or greater and an increase of more than 70 points from the baseline value, or initiation of treatment for active Crohn disease.
                For EPIC-1, 188 patients were assigned to receive omega-3 free fatty acids and 186 patients to receive placebo. Corresponding numbers for EPIC-2 were 189 and 190 patients, respectively. The rate of relapse at 1 year in EPIC-1 was 31.6% in patients who received omega-3 free fatty acids and 35.7% in those who received placebo (hazard ratio, 0.82; 95% confidence interval, 0.51-1.19; P = .30). Corresponding values for EPIC-2 were 47.8% and 48.8% (hazard ratio, 0.90; 95% confidence interval, 0.67-1.21; P = .48). Serious adverse events were uncommon and mostly related to Crohn disease.
                In these trials, treatment with omega-3 free fatty acids was not effective for the prevention of relapse in Crohn disease.
                clinicaltrials.gov Identifiers: EPIC-1: NCT00613197, EPIC-2: NCT00074542.
The use of conventional systemic corticosteroids in patients with clinically quiescent Crohn's disease does not appear to reduce the risk of relapse over a 24 month period of follow-up. An updated literature search performed in July 2008 did not identify any new trials.