Good Publication Practice for Communicating Company-Sponsored Medical Research: GPP3.

This updated Good Publication Practice (GPP) guideline, known as GPP3, builds on earlier versions and provides recommendations for individuals and organizations that contribute to the publication of research results sponsored or supported by pharmaceutical, medical device, diagnostics, and biotechnology companies. The recommendations are designed to help individuals and organizations maintain ethical and transparent publication practices and comply with legal and regulatory requirements. These recommendations cover publications in peer-reviewed journals and presentations (oral or poster) at scientific congresses. The International Society for Medical Publication Professionals invited more than 3000 professionals worldwide to apply for a position on the steering committee, or as a reviewer, for this guideline. The GPP2 authors reviewed all applications (n = 241) and assembled an 18-member steering committee that represented 7 countries and a diversity of publication professions and institutions. From the 174 selected reviewers, 94 sent comments on the second draft, which steering committee members incorporated after discussion and consensus. The resulting guideline includes new sections (Principles of Good Publication Practice for Company-Sponsored Medical Research, Data Sharing, Studies That Should Be Published, and Plagiarism), expands guidance on the International Committee of Medical Journal Editors' authorship criteria and common authorship issues, improves clarity on appropriate author payment and reimbursement, and expands information on the role of medical writers. By following good publication practices (including GPP3), individuals and organizations will show integrity; accountability; and responsibility for accurate, complete, and transparent reporting in their publications and presentations.

Bivalirudin: a review of its potential place in the management of acute coronary syndromes.

UNLABELLED: Bivalirudin, a synthetic analogue of hirudin, is a specific and reversible inhibitor of thrombin which binds directly with both fluid-phase and clot-bound thrombin. In patients with unstable angina undergoing percutaneous transluminal coronary angioplasty (PTCA), results from a large well designed study and its reanalysis (n = 4312) indicate that bivalirudin is more effective than heparin in the prevention of ischaemic complications for up to 90 days after the start of treatment. In addition, among patients undergoing PTCA for post myocardial infarction (MI) bivalirudin may be more effective than heparin in preventing ischaemic complications for up to 180 days after treatment was started. Data from dose-finding studies indicate bivalirudin has potential in the treatment of patients with unstable angina not undergoing percutaneous coronary intervention (PCI); however, well designed comparative studies are needed before firm conclusions can be made. Among patients with acute ST elevation MI, randomised trials have demonstrated bivalirudin to be significantly more effective than heparin in improving early patency in patients receiving thrombolytic therapy with streptokinase. Data from the Hirulog and Early Reperfusion/Occlusion (HERO)-1 trial (n = 412) indicate that bivalirudin recipients were significantly more likely to have Thrombin Inhibition in Myocardial Ischaemia (TIMI) grade 3 flow at 90 to 120 minutes than heparin recipients. In addition, data from the HERO-2 trial (n = 17 073) show bivalirudin was significantly more effective than heparin in reducing adjudicated 96-hour reinfarction and 30-day investigator-reported death/reinfarction than heparin. Bivalirudin was as effective as heparin in reducing 30-day mortality. Data from a meta-analysis of four randomised trials among patients undergoing PTCA or treatment for acute coronary syndromes indicate that, at after 30 to 50 days of follow-up, bivalirudin was significantly more effective than heparin in reducing the incidence of nonfatal MI and the combined endpoint of death or nonfatal MI. The most significant adverse events associated with bivalirudin are bleeding complications. In individual trials, bivalirudin was as well tolerated as heparin with, in general, a reduced incidence of bleeding complications. Additionally, bivalirudin provides a more consistent, predictable anticoagulant response. In 4312 patients with unstable angina undergoing PTCA the incidence of retroperitoneal bleeding, blood transfusion and major haemorrhage was significantly lower in bivalirudin than heparin recipients. Data from the HERO-2 trial in patients with acute MI indicate that although bivalirudin recipients had a significantly higher incidence of mild or moderate bleeding than heparin recipients, there was no difference in intracranial haemorrhage, severe bleeding or transfusions. Data from a meta-analysis among 5674 patients with ischaemic heart disease show bivalirudin recipients were at a significantly lower risk of haemorrhagic events than heparin recipients. CONCLUSIONS: Bivalirudin is an effective alternative to heparin in the prevention of ischaemic complications in patients with unstable angina undergoing PTCA. In addition, the drug has shown potential in the treatment of patients with unstable angina not undergoing PCI. For patients with MI, it is clear that bivalirudin can replace heparin in the management of MI where streptokinase is used as the thrombolytic agent. Further data are required on the efficacy of bivalirudin in patients undergoing thrombolysis with newer thrombolytics.

Losartan in diabetic nephropathy.

Losartan is an orally active, selective, nonpeptide, angiotensin II AT(1) receptor antagonist. Losartan 50 or 100 mg/day was significantly more effective than placebo in reducing the incidence of a doubling of serum creatinine, end-stage renal disease (ESRD) or death (43.5% vs 47.1%, p = 0.02) in a pivotal, well designed trial (Reduction of Endpoints in Non insulin dependent diabetes mellitus with the Angiotensin II Antagonist Losartan [RENAAL] study) in 1513 patients with type 2 diabetes mellitus and proteinuria. Losartan also significantly reduced the incidence of doubling of serum creatinine level (p = 0.006), ESRD (p = 0.002), ESRD or death (p = 0.01) and doubling of serum creatinine and ESRD (p = 0.01) compared with placebo in the RENAAL trial. There were similar incidences of overall mortality and morbidity and mortality from cardiovascular causes between treatment groups. In addition, data from several nonblind and double-blind studies indicates that losartan effectively reduces the mean albumin excretion rate. Two double-blind studies show that losartan has similar effects to enalapril on kidney function. Data from 4058 patients (3300 with essential hypertension) who have received losartan (10-150 mg/day) in clinical trials indicate it is well tolerated. In the RENAAL study 17.2% and 21.7% of losartan and placebo recipients discontinued treatment because of adverse events, but causality was not determined.

Bicalutamide: in early-stage prostate cancer.

Bicalutamide is an oral, once-daily nonsteroidal antiandrogen. Its efficacy in localised or locally advanced prostate cancer is currently being investigated as part of the Early Prostate Cancer (EPC) programme. In the EPC programme, bicalutamide 150 mg/day, as an adjunct to radiotherapy, radical prostatectomy or watchful waiting, significantly reduced the risk of objective disease progression, the incidence of bone metastases and the risk of prostate specific antigen progression compared with placebo (p < 0.0001 for all three parameters) after a median follow-up of 3 years. Survival data are currently immature, with an overall mortality rate of 6% in both treatment arms. On two nonblind, randomised trials, bicalutamide 150 mg/day monotherapy was as effective as medical or surgical castration in terms of overall survival in patients with locally advanced nonmetastatic prostate cancer. After a median follow-up of 6.3 years, median survival was 63.5 and 69.9 months for bicalutamide and castration, respectively; time to disease progression was also similar between treatment groups. Bicalutamide recipients reported a significantly smaller loss in sexual interest and a better physical capacity than recipients of castration (p

Rosuvastatin.

Rosuvastatin is a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor used in the treatment of patients with dyslipidaemia. Rosuvastatin is not extensively metabolised and has a low propensity for drug interactions. In well designed trials of between 6 and 52 weeks' duration, rosuvastatin was superior to atorvastatin, simvastatin and pravastatin in improving the lipid profile of patients with hypercholesterolaemia. In a 1-year dose-titration study, rosuvastatin 13.4mg daily (mean dose) allowed more patients to achieve US National Cholesterol Education Program (Adult Treatment panel II)[NCEP] target low-density lipoprotein (LDL)-cholesterol levels than atorvastatin 20.8mg daily (98 vs 87%) with the difference most marked in high-risk patients (97 vs 61%). Similarly, when compared with pravastatin and simvastatin 20 mg/day in a further 1-year trial, 88% of rosuvastatin recipients [9.5 and 13.8 mg/day (mean doses)] achieved NCEP target serum LDL-cholesterol levels compared with 60 and 73% of pravastatin and simvastatin recipients, respectively, with the difference more marked in high-risk patients. In further clinical trials, rosuvastatin improved the lipid profile of patients with heterozygous or homozygous familial hypercholesterolaemia, hypertriglyceridaemia or mixed dyslipidaemias. Rosuvastatin was well tolerated in clinical trials of up to 1 years' duration.

A comparison of two experimental design approaches in applying conjoint analysis in patient-centered outcomes research: a randomized trial.

BACKGROUND: While the application of conjoint analysis and discrete-choice experiments in health are now widely accepted, a healthy debate exists around competing approaches to experimental design. There remains, however, a paucity of experimental evidence comparing competing design approaches and their impact on the application of these methods in patient-centered outcomes research. OBJECTIVES: Our objectives were to directly compare the choice-model parameters and predictions of an orthogonal and a D-efficient experimental design using a randomized trial (i.e., an experiment on experiments) within an application of conjoint analysis studying patient-centered outcomes among outpatients diagnosed with schizophrenia in Germany. METHODS: Outpatients diagnosed with schizophrenia were surveyed and randomized to receive choice tasks developed using either an orthogonal or a D-efficient experimental design. The choice tasks elicited judgments from the respondents as to which of two patient profiles (varying across seven outcomes and process attributes) was preferable from their own perspective. The results from the two survey designs were analyzed using the multinomial logit model, and the resulting parameter estimates and their robust standard errors were compared across the two arms of the study (i.e., the orthogonal and D-efficient designs). The predictive performances of the two resulting models were also compared by computing their percentage of survey responses classified correctly, and the potential for variation in scale between the two designs of the experiments was tested statistically and explored graphically. RESULTS: The results of the two models were statistically identical. No difference was found using an overall chi-squared test of equality for the seven parameters (p = 0.69) or via uncorrected pairwise comparisons of the parameter estimates (p-values ranged from 0.30 to 0.98). The D-efficient design resulted in directionally smaller standard errors for six of the seven parameters, of which only two were statistically significant, and no differences were found in the observed D-efficiencies of their standard errors (p = 0.62). The D-efficient design resulted in poorer predictive performance, but this was not significant (p = 0.73); there was some evidence that the parameters of the D-efficient design were biased marginally towards the null. While no statistical difference in scale was detected between the two designs (p = 0.74), the D-efficient design had a higher relative scale (1.06). This could be observed when the parameters were explored graphically, as the D-efficient parameters were lower. CONCLUSIONS: Our results indicate that orthogonal and D-efficient experimental designs have produced results that are statistically equivalent. This said, we have identified several qualitative findings that speak to the potential differences in these results that may have been statistically identified in a larger sample. While more comparative studies focused on the statistical efficiency of competing design strategies are needed, a more pressing research problem is to document the impact the experimental design has on respondent efficiency.