BCG vaccination and leprosy protection: review of current evidence and status of BCG in leprosy control.

The bacillus Calmette-Guérin (BCG) vaccine, initially developed to provide protection against TB, also protects against leprosy; and the magnitude of this effect varies. Previous meta-analyses did not provide a summary estimate of the efficacy due to the heterogeneity of the results. We conducted a meta-analysis of published data including recently published studies (up to June 2009) to determine the efficacy of BCG protection on leprosy and to investigate whether age at vaccination, clinical form, number of doses, type of study, the latitude of study area and year of publication influence the degree of efficacy and explain the variation. In the light of the results, we argue for more emphasis on the role of BCG vaccination in leprosy control and research

A pivotal registration phase III, multicenter, randomized tuberculosis controlled trial: design issues and lessons learnt from the Gatifloxacin for TB (OFLOTUB) project

<p>Abstract</p> <p>Background</p> <p>There have been no major advances in tuberculosis (TB) drug development since the first East African/British Medical Research Council short course chemotherapy trial 35 years ago. Since then, the landscape for conducting TB clinical trials has profoundly changed with the emergence of HIV infection, the spread of resistant TB bacilli strains, recent advances in mycobacteriological capacity, and drug discovery. As a consequence questions have arisen on the most appropriate approach to design and conduct current TB trials. To highlight key issues discussed: Is a superiority, equivalence, or non-inferiority design most appropriate? What should be the primary efficacy outcome? How to consider re-infections in the definition of the outcome? What is the optimal length of patient follow-up? Is blinding appropriate when treatment duration in test arm is shorter? What are the appropriate assumptions for sample size calculation?</p> <p>Methods</p> <p>Various drugs are currently in the development pipeline. We are presenting in this paper the design of the most recently completed phase III TB trial, the OFLOTUB project, which is the pivotal trial of a registration portfolio for a gatifloxacin-containing TB regimen. It is a randomized, open-label, multicenter, controlled trial aiming to evaluate the efficacy and safety of a gatifloxacin-containing 4-month regimen (trial registration: ClinicalTrial.gov database: NCT00216385).</p> <p>Results</p> <p>In the light of the recent scientific and regulatory discussions, we discuss some of the design issues in TB clinical trials and more specifically the reasons that guided our choices, in order to best answer the trial objectives, while at the same time satisfying regulatory authority requirements.</p> <p>Conclusion</p> <p>When shortening TB treatment, we are advocating for a non-inferiority, non-blinded design, with a composite unfavorable endpoint assessed 12 months post treatment completion, and added trial procedures specifically aiming to: (1) minimize endpoint unavailability; and (2) distinguish between relapse and re-infection.</p