Redundant surgical publications: tip of the iceberg?

BACKGROUND: A redundant publication is one which duplicates previous, simultaneous, or future publications by the same author or group or, alternatively, could have been combined with the latter into one paper. As there is no information about the extent of this problem in the surgical literature, we set out to assess the incidence, spectrum, and salient characteristics of redundant publications in 3 leading surgical journals. METHODS: Original articles (excluding reviews, editorials, abstracts, and letters) published during 1998 in the journals Surgery, The British Journal of Surgery, and Archives of Surgery were searched by using the on-line search engine PUBMED. Each original article was scrutinized to identify redundancy by combining the names of the first, second, and last authors with a few key words from the title. Papers were defined as "suspected" redundant publications if they were found to address the same topic as the "index" article and shared some or most of the elements of methodology, results, or conclusions. The full versions of all suspected papers were retrieved and compared with the index articles. A grading system was developed to define several types of redundant publications: A. "dual"; B. "potentially dual"; C. "salami-slicing." RESULTS: A total of 660 articles were screened. There were 92 index articles (14%) leading to 147 suspected papers found in other journals, representing some potential form of a redundant publication. The vast majority of suspected papers were published within approximately a year of the index paper and were not cited by the latter. Most (69%) of the suspected papers were also published in surgical journals. Only 12 (8.1%) appeared in, or originated from, a "local-foreign" journal. Twenty (13.6%) of the suspected papers met the criteria for dual publications, 50 (34%) for potentially dual publications, and 77 (52.4%) were considered products of salami-slicing. CONCLUSIONS: Almost 1 in every 6 original articles published in leading surgical journals represents some form of redundancy. Current on-line search technology provides an effective tool for identifying and tracing such publications, but it is not used routinely as part of the peer review process. Redundancies occur in several well-defined patterns; the phenomenon is widespread, and it cuts across the entire spectrum of surgeons in the United States and abroad. Redundant publications must be recognized not as a mere nuisance but as a real threat to the quality and intellectual impact of surgical publishing.     

Is it still ethical to conduct clinical trials against a placebo? A review of the ethical and methodological controversy

A DEVELOPING CONTROVERSY: The marketing authorization for new drugs from the regulatory authorities'and ethical point of view, is only possible following convincing proof of their efficacy and safety. Between the drug registration authorities, who underline the necessity of early assessment against a placebo, on the one hand, and the ethical and consumer committees that disapprove of the use, the controversy has developed. FOR METHODOLOGISTS: Comparisons with reference drugs provide less credible results that comparisons versus a placebo. This is why their exclusive use may have deleterious effects on the reliable assessment of products to be launched on the market, in terms of efficacy and safety. Equivalence trials do not provide the expected solution since their internal validation requires a placebo arm. RETICENCE BUT NO PROHIBITION: The fifth revision of the declaration of Helsinki by the World medical association in the year 2000, which led to violent controversy regarding the drawing-up of section 29 and its clarification note, does not really help the debate progress: the authors of the texts confirm their reticence to the use of a placebo, but do not prohibit it. They have chosen a "middle of the road" solution. IN PRACTICE: The decision to conduct or not a placebo-controlled study should take into account the aims of the study (within the context or not of a marketing authorization submittal by an industrial), the early stage of the development of the drug or not and, above all, the level of efficacy and safety of the drugs already available versus the anticipated effects of the new product.     

Negative results of randomized clinical trials published in the surgical literature: equivalency or error?

HYPOTHESIS: We hypothesized that review of randomized controlled clinical trials (RCTs) with nonstatistically significant or "negative" results published in the surgical literature do not have appropriate statistical power to demonstrate equivalency between treatment arms. DATA SOURCES AND STUDY SELECTION: The MEDLINE database was searched to obtain reports of all RCTs with negative results published in 3 surgical journals from 1988 to 1998. Manual review of one year (1997) of publications for each journal was performed to validate our search strategy. Equivalency was evaluated using the Two One-Sided Tests Procedure and post hoc power calculations. DATA SYNTHESIS: Ninety reports of RCTs with negative results were identified in the surgical literature between 1988 and 1998. The manual review of 1997 showed a 100% retrieval rate for our search strategy. After applying the Two One-Sided Tests Procedure, 35 reports (39%) met the criteria for demonstrating equivalency. The other 55 reports (61%) contained at least a 10% absolute difference in the 90% confidence interval of Delta. Using the power calculation method, only 22 (24%) articles had a power greater than.80 to detect a 50% difference in therapeutic effect. Only 29% of the reports included a formal sample size calculation and these studies were more likely to demonstrate equivalency than those without a sample size estimate (P<.01). CONCLUSIONS: Many reports from negative RCTs published in the surgical literature lack sufficient statistical power to establish that clinically important differences are not present. Surgeons should perform appropriate sample size calculations when designing RCTs and recognize the utility of confidence intervals when reporting negative results.     

Dent’s disease manifesting as focal glomerulosclerosis: Is it the tip of the iceberg?

Dent’s disease is an X-linked proximal tubulopathy. It often manifests in childhood with symptoms of Fanconi syndrome and low-molecular-weight proteinuria. We describe four boys from three unrelated families whose only presenting symptoms of Dent’s disease were nephrotic-range proteinuria and histological findings of focal segmental and/or global glomerulosclerosis. In all families, a causal mutation in the CLCN5 gene, encoding a voltage-gated chloride transporter and chloride-proton exchanger, was identified. All three mutations are pathogenic: two are novel (p.Asp727fs and p.Trp122X), and one is a recurrent mutation, p.R648X. Given the atypical phenotype of these patients with Dent’s disease, it is possible that this clinical entity is markedly underdiagnosed and that our report represents only the tip of the iceberg. The diagnosis of Dent’s disease should be considered in all patients with nephrotic-range proteinuria without hypoalbuminemia or edema. Establishing the diagnosis of Dent’s disease will prevent the administration of unnecessary immunosuppressive medications with their undesirable side effects.     

Mesh erosion into the urinary bladder following laparoscopic inguinal hernia repair; is this the tip of the iceberg?

A 67-year-old man presented with recurrent sepsis, groin swelling, and lower urinary tract symptoms 12 years after bilateral TEP inguinal hernia repair. Diagnosis of mesh migration and erosion into the urinary bladder was made by cystoscopy. Exploration of the groin confirmed Prolene mesh erosion into the lateral wall of the urinary bladder. This is the second reported case following TEP repair. A review of the literature reveals eight reported cases following laparoscopic repair since 1994. The factors contributing to mesh migration and erosion are discussed. With large case series of mesh non-fixation being reported in world literature, it may be that the incidence of this complication will increase in the future. A lower diagnostic threshold and reporting of this complication should be encouraged.     

Is it ethical to conduct placebo-controlled clinical trials in the development of new agents for osteoporosis? An industry perspective.

To represent industry on the topic of this conference, position papers were obtained from six pharmaceutical and biotechnology companies. Despite their holding a wide range of positions in the market with regard to prevention and treatment of osteoporosis, all companies were unanimous in their concerns about the ability to conduct randomized placebo-controlled clinical trials (PCTs) in the future. The clinical research environment contains conflicting directives. Regulatory agencies strongly prefer (even insist on) PCTs as a requirement for drug approval, while many physicians, human studies institutional review boards, and informed patients believe that it is no longer ethical to place osteoporotic patients on placebo because effective therapies are now available. PCTs offer the best means of calibrating the absolute efficacy of a new agent and identifying its side effects against a "neutral" background. Are comparison-controlled clinical trials (CCTs) using an approved drug the answer? No. Examples are given that illustrate that such trials require very large numbers of patients to show "non-inferiority" (approximately 15,000-20,000) or "superiority" (approximately 30,000) compared with an existing approved therapy. Such studies are not only impractical, but also accumulate a greater number of fractures during the course of clinical research in both the new treatment and control (active comparator) groups than would occur in PCTs. Total adverse experiences and exposure of patients to investigational agents is considerably greater when CCTs rather than PCTs are used. Based on this analysis, industry recommends that regulatory approval of new agents for osteoporosis be based on (1) conduct of PCTs in patients at low risk for fracture (e.g., T-score < -2.5 and no previous osteoporotic fracture); (2) use of bone mineral density as an end-point for the indication "to preserve or improve bone mass"; (3) a 2-year, rather than 3-year, trial period; (4) demonstration of no adverse effect on bone quality preclinically; (5) extrapolation of clinical trial results to higher risk patients; (6) an option for the sponsor to perform additional fracture end-point studies postapproval to obtain an indication for "treatment to reduce the risk of fractures specifically in the spine, hip, or both"; and (7) the option to file for a "prevention" claim before a "treatment" claim.