Reporting bias in medical research - a narrative review

Reporting bias represents a major problem in the assessment of health care interventions. Several prominent cases have been described in the literature, for example, in the reporting of trials of antidepressants, Class I anti-arrhythmic drugs, and selective COX-2 inhibitors. The aim of this narrative review is to gain an overview of reporting bias in the medical literature, focussing on publication bias and selective outcome reporting. We explore whether these types of bias have been shown in areas beyond the well-known cases noted above, in order to gain an impression of how widespread the problem is. For this purpose, we screened relevant articles on reporting bias that had previously been obtained by the German Institute for Quality and Efficiency in Health Care in the context of its health technology assessment reports and other research work, together with the reference lists of these articles

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Charged-particle multiplicity distributions over a wide pseudorapidity range in proton-proton collisions at root s=0.9, 7, and 8 TeV

We present the charged-particle multiplicity distributions over a wide pseudorapidity range ( $-\,3.4<\eta <5.0$ ) for pp collisions at $\sqrt{s}= 0.9, 7$ , and 8 TeV at the LHC. Results are based on information from the Silicon Pixel Detector and the Forward Multiplicity Detector of ALICE, extending the pseudorapidity coverage of the earlier publications and the high-multiplicity reach. The measurements are compared to results from the CMS experiment and to PYTHIA, PHOJET and EPOS LHC event generators, as well as IP-Glasma calculations.We present the charged-particle multiplicity distributions over a wide pseudorapidity range ($-3.4<\eta<5.0$) for pp collisions at $\sqrt{s}=$ 0.9, 7, and 8 TeV at the LHC. Results are based on information from the Silicon Pixel Detector and the Forward Multiplicity Detector of ALICE, extending the pseudorapidity coverage of the earlier publications and the high-multiplicity reach. The measurements are compared to results from the CMS experiment and to PYTHIA, PHOJET and EPOS LHC event generators, as well as IP-Glasma calculations

Charged-particle multiplicity distributions over a wide pseudorapidity range in proton-proton collisions at root s=0.9, 7, and 8 TeV

We present the charged-particle multiplicity distributions over a wide pseudorapidity range ( $-\,3.4<\eta <5.0$ ) for pp collisions at $\sqrt{s}= 0.9, 7$ , and 8 TeV at the LHC. Results are based on information from the Silicon Pixel Detector and the Forward Multiplicity Detector of ALICE, extending the pseudorapidity coverage of the earlier publications and the high-multiplicity reach. The measurements are compared to results from the CMS experiment and to PYTHIA, PHOJET and EPOS LHC event generators, as well as IP-Glasma calculations.We present the charged-particle multiplicity distributions over a wide pseudorapidity range ($-3.4<\eta<5.0$) for pp collisions at $\sqrt{s}=$ 0.9, 7, and 8 TeV at the LHC. Results are based on information from the Silicon Pixel Detector and the Forward Multiplicity Detector of ALICE, extending the pseudorapidity coverage of the earlier publications and the high-multiplicity reach. The measurements are compared to results from the CMS experiment and to PYTHIA, PHOJET and EPOS LHC event generators, as well as IP-Glasma calculations

Multicenter Study on Spreading of the tet(M) Gene in Tetracycline-Resistant Streptococcus Group G and C Isolates in Argentina

A prospective multicenter study on invasive infections caused by beta-hemolytic streptococci was performed over 6 months and involved 42 centers from 16 cities in Argentina. Among 33 isolates recovered, 9 group G Streptococcus isolates (39.1%) and 2 group C Streptococcus isolates (20%) exhibited resistance to tetracycline and harbored the tet(M) gene. Genealogical analysis revealed that tetracycline resistance has a polyclonal origin in Argentina