Use of inappropriate stopping rules for clinical trials results in an excess of false positive conclusions when no true survival differences exist. Overviews of such trials, however, consist mainly of trials which were not stopped early, plus a few of reduced sample size which were. Simulations confirm that the level of such an overview is minimally elevated. Additional follow-up for survival further corrects the level. In fact, for individual trials conducted according to inappropriate rules, late tests have nearly correct level. On the other hand, publication bias (differential reporting of positive results) can substantially increase the level of an overview if only published studies are included.

Clinical Trials as Topic↗

PubMedDate not supplied

Antiproliferative effect of nonsteroidal antiinflammatory drugs against human colon cancer cells.

Several lines of evidence suggest that nonsteroidal antiinflammatory drugs may be effective in preventing colorectal cancer. These include animal experiments, case-control studies, and clinical experience with sulindac in promoting the regression of adenomatous colon polyps in adenomatous polyposis coli. We determined the antiproliferative activity of various nonsteroidal antiinflammatory drugs, including two sulindac derivatives, against human colon cancer cells in vitro. Ht-29, SW480, and DLD-1 cells were continuously incubated with serial drug dilutions for 6 days prior to fixation. Cell number was determined using the sulforhodamine B assay, and drug concentrations which inhibited cell growth by 50% were estimated for each agent by interpolation. All drugs exhibited antiproliferative activity against Ht-29 and DLD-1 cells, and most inhibited SW480 cells. For Ht-29 cells, the 50% inhibitory concentration varied from 55 microM for diclofenac to 2100 microM for 5-aminosalicylic acid, with three drug groups of high, intermediate, and low potency evident. Inhibition of cell growth by sulindac sulfide was reversible following drug removal. Nonsteroidal antiinflammatory drugs exert an antiproliferative effect against human colon cancer cells with a wide range of potencies. A cytostatic response was demonstrated with sulindac sulfide. These data further support the potential role of these agents for chemoprevention of colorectal neoplasia.

Anti-Inflammatory Agents, Non-Steroidal↗