Bittman Biostat, Inc.

Statistical Consulting for Pharmaceutical & Device Development   

Case Studies

Chair a DSMB. A sponsor required a chair for a Data Safety Monitoring Board whose medical members’ clinical workloads left minimal time for committee work. Dr. Bittman chaired the DSMB and prepared reports, as well as organized the statistical analysis and sourced and supervised the statistical programming.

Mock panel participation. A regulatory consulting organization anticipated challenges by an FDA advisory committee to their client’s device submission. The organization engaged Dr. Bittman to serve as the biostatistician in a mock panel that would simulate the actual committee meeting.

Complex modeling of a functional safety outcome. A client inherited a large observational study for an important side effect of a recently acquired product. Dr. Bittman developed a random coefficients model to predict longitudinal changes in the outcome and assess the effect of treatment exposure on function.

Defining non-inferiority margins. A new therapy may be as efficacious as the standard of care, but have a safer side-effect profile. A non-inferiority trial can demonstrate that the efficacy of the new therapy is within a numerical margin of current therapy. Pre-specifying a margin acceptable to regulatory authorities requires a unique combination of statistical and clinical judgment. Dr. Bittman has helped several companies define margins for cardiovascular outcomes trials.

Interpreting clinical trial results for a legal case. The assessment of clinical trial results depends not only on the data but on how endpoints were specified: Was the horse picked before the race began or when it was near the finish line? To help his trial attorney client evaluate strengths and weaknesses of the case, Dr. Bittman assessed project communications and clinical trial protocols and reports with respect to established principles of clinical research, statistical theory and regulatory practice.

Predicting clinical trial outcomes for investors. Investors and the Board of Directors of a privately held company needed to know the likelihood of success of a key clinical trial. Because the trial was blinded and ongoing, Dr. Bittman prepared hypothetical scenarios to show how the probability of attaining statistical significance depended on key assumptions.

Advisory Committee preparation. Having consulted with a client from inception of a project, Dr. Bittman joined the clinical and regulatory team to prepare for the Advisory Committee. He identified a key supplemental analysis that would solidify the primary finding of the single efficacy study. The result became the key piece of evidence that FDA itself called to the attention of its Advisory Committee. The Committee voted in favor of approval.

Press release. The client, a publicly-traded company, had a short period of time to release results of a completed clinical study with mixed results. Dr. Bittman, who was formerly a newspaper reporter, worked with the clinical and management team to both highlight the promise of the therapy and maintain scientific validity of the reporting.

Remote technical supervision. A small company needed guidance for an on-site junior statistician tasked with unstructured exploratory data analysis. Dr. Bittman provided methodological direction and periodic coaching by telephone and email.

New methodology for efficacy evaluation. A large Pharma client desired to stay in the forefront of methodological research by developing a data analysis technique that could have saved a completed trial, had it been available at the time of protocol development. Dr. Bittman, a company statistician and academic researchers developed a method and published it in a leading statistical journal.

SOPs for ISO 9000 certification. A Contract Research Organization applying for ISO certification needed a complete set of statistics and data management SOPs. Dr. Bittman and client management co-developed the required documents, leading to a successful audit by ISO evaluators.

Retrospective application of guidelines. FDA, while reviewing a client’s NDA submission, asked the client to apply current therapeutic success criteria to several studies completed before the guidelines were published. Collaborating with the project team, Dr. Bittman provided a rational basis for excluding studies for which a retrospective analysis was not feasible and for adapting the criteria to the remaining studies.

Bioequivalence of highly variable drugs. A drug could be so variable that it would not be considered bioequivalent to itself under the traditional 80-125% limits. A proposed FDA guidance defines an alternative criterion. For a client with a potentially highly variable drug, Dr. Bittman compared sample size under the traditional and alternative criteria, using computer simulations and historical data. The comparison pointed the way to the approach the client would use for its bioequivalence study.

 

 

FOR INFORMATION PLEASE CONTACT:
Dr. Richard M. Bittman
9047 Cherry Oaks Trail #202
Naples, Florida 34114
Phone: 239.970.0536
Email: rmb@bittmanbiostat.com