Success stories

Situation: Rho was contracted to run a phase II bunionectomy trial where managing timelines was critical to our sponsor.

Rho’s solution:The keys to their success:

• Strong site relationships and experienced CRAs helped them complete enrollment of the trial's 500 subjects 7 weeks ahead of schedule.
• A dedicated study start-up team ensured that all IRB pprovals were in place within three months and that site contracts were negotiated and fully executed within 2 weeks of IRB approval.
• Through the highly coordinated efforts of our data anagement professions, the database was locked a full month ahead of schedule.

Situation: Rho supported an FDA post-submission safety review on a short timeline.

Rho’s solution: We created Study Data Tabulation Model (SDTM)–compliant data sets for nine clinical trials conducted over the past 10 years, a challenging feat with limited documentation concerning old data. Because of the urgency of the request, Rho successfully created the data sets in 1 month. To further support the review, Rho created six meta-analysis data sets for 41 studies in 2 months. Rho’s immediate response and turnaround enabled the client to respond to FDA queries with information leading to a satisfactory safety review result.

Situation: Rho was asked to support two ongoing phase 3 pivotal trials. Our investigation discovered that a lack of oversight and management and poor protocol execution and compliance had led to inaccuracies that put this trial at risk.

Rho’s solution: We provided oversight and guidance to ensure site compliance, quality data, as well as statistically sound analysis. We expedited all monitoring activities as enrollment was complete and provided efficient collection and editing of the data. As issues arose and major regulatory violations were found, Rho created a risk analysis plan to help guide the client through the multitude of issues. At the request of the client, Rho provided advice on how to repair their relationship with the FDA and assisted in drafting response letters to the FDA. After completion of the analysis, Rho collaborated with the client to appropriately communicate the final study results in the serial investigational new drug (IND) submission.

Situation: The FDA removed a previously approved medical device from the market because of safety concerns. The length of and decisions surrounding the original approval process, combined with safety concerns that were not yet substantiated, resulted in rejection of the client’s attempts to regain marketing authorization from the FDA.

Rho’s solution: We proposed a cascading study design that definitively addressed the FDA’s concerns and met the agency’s criteria for approval. After approval and the client’s implementation of this study design, the FDA allowed this device back on the market.

Situation: Another of Rho’s clients was attempting to develop a drug for traumatic brain injury. A Rho senior scientist advised that the client’s sample size could be reduced by two thirds through the use of mixed-model analysis, an approach new to the central nervous system (CNS) division of the FDA at that time.

Rho’s solution: The Rho scientist accompanied the client to the FDA, taught the lead statistician of the CNS division how to use mixed-model analysis, and convinced him of its viability. Though the drug eventually proved unsuccessful, Rho saved this client a significant amount of money and time by reducing their sample size while increasing the number of statistical methods allowed by the CNS division.

Situation: Recently, one of Rho’s clients submitted a common technical document (CTD) application to the Therapeutic Goods Administration (TGA)—Australia’s regulatory agency. After their application was denied three times, the client appealed to the Parliamentary Secretary to the Minister for Health and Aging, a cabinet-level position. The project would be canceled if this last appeal was not successful.

Rho’s solution: During this rescue, our Chief Scientific Officer assisted in the final appeal. This statistician perused the client’s entire dossier. After reviewing the TGA’s responses and the sponsor’s trial results, Rho confirmed which TGA concerns were valid, and we corrected prior assumptions and conclusions that were incorrect. We presented our findings in an 80-page report. After submission of the revised report, the drug was approved and is currently on the market in Australia.

Situation: A client’s competitor was about to publish a paper reporting that our client’s medical device could be linked to a serious health condition in patients who used the device.

Rho’s solution: Our Chief Scientific Officer and staff worked around the clock investigating methods used in the upcoming article. We soon discovered that the authors of the article were erroneously using an inappropriate statistical model in the analysis. We repeated the analysis using appropriate methods for handling small sample sizes and the correct sample subjects and proved that the risk of the serious health condition was not significantly different from the risk in subjects who did not use the device. Our expertise and quick response to our client enabled them to defend the safety of their medical device.

Situation: A client developing a drug for chronic pain was concerned that informative censoring would occur in their clinical trial. Informative censoring is common in this therapeutic area. The FDA, taking a conservative approach, preferred an imputation technique wherein missing observations for a subject who withdrew from the trial were imputed with that subject's baseline observations. This imputation method has the potential to introduce a large bias against the active treatment.

Rho’s solution: Our team employed simulations based on a masked snapshot of the trial data to compare the bias of the FDA’s recommended imputation method to other viable, state-of-the-art methods for missing data. The simulation scenarios were designed to assess the methods under a variety of increasingly complex circumstances. While this is still a work in progress, Rho is helping this client convince the FDA that there are alternative analytical methods that will increase accuracy, reduce bias, and thus increase the chances that a potentially valuable new drug will reach market.