WHICH PRODUCT IS MOST LIKELY TO BE BIOEQUIVALENT
APS helped our company work through a series of potential oral generic drug formulations, designed to match reference-listed drug products. They used statistical methods to compare the results of in vitro and pilot bioequivalence study results to allow us to make an informed choice from among the test products. The best candidate was then carried forward and found to be bioequivalent. Thank you.
ALLOWING RISKS TO COMPETE WITHIN A CLINICAL TRIAL
Our oncology start-up was performing a time to event clinical trial, with survival analysis methods used for the efficacy assessment. As the study moved forward it became very important for us to accurately predict the time of trial completion to allow for better management of the clinical trial sites, employee resources, and finances. APS put together a competing risks model, based on data from the ongoing trial (still blinded) that allowed us to accurately predict when the study endpoint would be reached.
CLINICAL TRIAL SIMULATIONS
Our oncology startup was in the midst of performing a clinical trial with a survival endpoint. Some recent publications drove us to perform a sensitivity analysis around our primary trial endpoint, to address questions such as: What if the timing of events was very different than anticipated between the two treatment groups? That is, what if one treatment group reported events very early while the other reported events late? How could this change the overall median time to event (median survival) for the two treatment arms? How might the different enrolled patient phenotype subgroups impact the primary study outcome, based upon more recent data? How quickly were study endpoints accruing, and is the observed rate consistent with our Statistical Analysis Plan assumptions? APS worked with us to develop a very detailed, blinded, enrollment report, that was used to gauge trial progress on a monthly basis. The report included tables and graphs that broke the information down in an manner in an easy to follow format. As the trial continued we came up with new questions, and APS was able to add additional tables and graphs to the report, which made them even more useful. With this information we were able to provide more accurate reporting to our patients, investigators, clinical sites and others. Thank you APS.
APS is working with us on an ongoing basis to develop protein-based biosimilar products. With the help of APS we have put together a series of in vitro test methods that characterize the products, some of which test for equivalence between our products and the RLD products. APS not only monitors and reports on the projects, they’ve been able to advise us on choosing the laboratories to work with (i.e. outsourcing). The breadth of experience at APS has been a huge asset to our program. Thank you APS.
CLINICAL TRIAL MATERIAL PACKAGING FOR PHASE 2/3
Our CDMO focuses on commercial formulation development. For an NDA client, we were asked to put together a clinical trial material (CTM) program for planned Phase 1, 2, and 3 studies. These varied from single site to multi-year, multi-product, international, randomized, blinded, and controlled clinical trials. We clearly needed help to meet the client’s needs.
APS developed a series of SAS programs and a data collection tools, into which key clinical protocol information and finished product information was extracted and combined to create a single master packaging plan (MPP) for sponsor review. The MPP covered all studies and development phases. The detail in the MPP was exquisite and included finished product specifications, all label fields for all countries, all packaging specifications and other key information. The programs developed produced critical GMP batch record pages to guide packaging, including for the pre-randomized and blinded products.
APS also put together the randomization codes, for all protocols, patient strata, and sites. APS worked directly with label printers and the packaging material manufacturers to get these clinical packaging supplies to our CDMO in time for the packaging runs to start. Once packaging was complete APS was able to work with our statisticians, regulatory staff, and the IVRS system vendor to assist with trial startup. They also developed a protocol enrollment and progress report for the Sponsor. Their unique understanding of clinical trial packaging requirements and GMP procedures, in addition programming and reporting allowed our project to move forward as planned.
HOW TO PERFORM AN INTERIM CLINICAL TRIAL ANALYSIS
We included an interim analysis for efficacy and futility into our phase III oncology protocol and SAP. However, as the interim analysis milestone approached, it became clear that additional guidance was needed for both the CRO and the DSMB. As study Sponsor, we wanted to prospectively verify that the CRO/DSMB unblinded statistician was able to perform the necessary analysis procedures, given the importance of this analysis to study patients, and our company. APS setup a quality control program in advance of the analysis, working directly with the CRO statisticians. Together they established and verified the analysis programs, verified calculated results, and settled on the printed output that would be provided to the DSMB. Ultimately, the interim analysis moved ahead very smoothly to the satisfaction of all, which was very important for us.