The Staburo Managing Directors Josef Hoefler and Roland Stieger had the opportunity to join the AGAH Annual Meeting in April 2018, here in Munich.

The conference focused on how to prevent or predict adverse drug reactions in early phase drug development. The major target organ systems were liver, kidney, CNS, cardiac function. Further sessions were dedicated to local tolerance and immunotoxicity.

The following questions were addressed in excellent expert talks and panel discussions.

• How can animal models and in vitro data help to estimate risk regarding human administration?
• How can kidney and liver function best be monitored in the settings of early phase trials?
• What do we need to know to assess potential CNS adverse drug reactions early on?
• What are the pathophysiological mechanisms leading to potential cardiac toxicity?
• What are the guidelines on non-clinical local tolerance testing?
• How to monitor immunotoxicity in novel immunological therapies?

The conference gave participants the opportunity to discuss these and additional questions with expert speakers, regulators and ethic committees members as well as colleagues from pharmaceutical industry, CRO and academia.

The meeting started with a one-day pre-conference workshop about basic terms and key concepts of pharmacovigilance with a strong focus on early phase drug development. This workshop offered an excellent preparation for the annual meeting for those who are not yet experts in the field.

Staburo participated in the conference and the networking opportunities and we were very happy to get to know new people in the field of clinical trials and to catch up with partners from client companies. Thank you for this great event in Munich!

Staburo at the Biometric Colloquium 2018 in Frankfurt

Staburo participated in the 64th Biometric Colloquium 2018 in Frankfurt, the annual meeting of the German Region of the International Biometric Society (IBS-DR). The conference was hosted by the faculty of medicine at the Goethe University and statisticians from pharmaceutical industry, academia and regulatory agencies from all over the world attended. The Colloquium’s main topic was “Biometry: Living Diversity”, which promised interesting talks, great discussions and new insights to a variety of topics. Some of the themes were “Bayesian Approaches”, “Survival Analysis”, “Adaptive Designs” and “Meta Analysis”, but also hot emerging topics as “Estimands and Missing Values in Clinical Trials” and “Health Technology Assessment” were discussed with statistics experts. On the other hand, more technical presentations about “Machine Learning”, “Multiple Testing” or “Non-parametric Methods” were held.

The reception in Frankfurt’s town hall and the conference dinner in the “Eisenhower Rotunde” at the Goethe University Frankfurt offered a great opportunity to meet participants and speakers of the conference, in a very festive environment. We are looking forward to next year’s conference!

Tumour growth over time

Longitudinal Data, Joint Models, and Surrogate Endpoints for Survival Analysis

Tumour burden has been shown to be associated with clinical outcomes in many oncological indications. To explore the impact of treatment on tumour growth over time, all available tumour measurements can be used. Patients with at least two valid tumour images and corresponding sum of diameters of target lesions, measured by RECIST, contribute to the Tumour-growth-Model. Mixed-effects models can be used to quantify the non-linear individual relationships between time from randomization and tumour burden. The model needs to be flexible, allowing for a wide range of different shaped growth curves (u-shaped, j‑shaped, n-shaped, linear-shaped). Finding the optimal parameterisation via AIC and visual inspection of all individual fits, is time consuming but crucial. Such a Tumour-Growth-Model can be used to

• better understand the mode of action and investigate other factors influencing tumour growth
• investigate the influence of tumour kinetics on survival
• develop new (additional) surrogate endpoints for overall survival to improve future phase II go/no-go decisions
• improve future early PFS estimation in the same indication and line.

If you are interested in this topic, feel free to contact us anytime!

Biomarkers that help patients to choose the best treatment option, play a key role in drug development and precision medicine. The talk introduced the Virtual Twin Method by Foster et al. (2011). It is a multivariate, tree-based method that identifies patients who may benefit from a certain treatment. The close relationship to prognostic and predictive biomarkers was illustrated, and the advantages and disadvantages compared to univariate methods were highlighted. This internal Staburo training was a great opportunity to share knowledge within our team and to start a very fruitful discussion about the Virtual Twin Method!

The Engaged Database – TED

With TED, users have access to a straightforward tool, based upon the European Medicines Agency (EMA) inspection database, which allows the comparison of the results of one or more audits, to a large number of audit results. The Engaged Database is owned and managed by Dr. Barbara Heumann, who also owns the independent auditing company, GXP Engaged Auditing Services.

Staburo’s contribution to TED

Staburo was already involved early in the development of TED, and majorly responsible for the creation of the PDF reports. The benefit for the users of TED is putting their audit results in context to all other entries in TED. These reports are created automatically, using the R programming software, implemented directly in an interface within the SQL data base. Staburo programmed the automatic creation of reports, and implemented it together with a data base programming provider. We communicated with and between the involved parties (GXP Engaged Auditing Services, data base programming, design expert, validation), provided statistical advice for the various elements inside the reports, balanced design and scientific soundness, implemented style requirements, and did (in parts) data validation.

Welcome our teammates Hans and Bobby!

We are very glad to welcome Hans Bauer and Bobby Reidy in our team. Hans and Bobby are both professionals with work experience and excellent education from first-class universities. They will support our clients in the areas of biostatistics & statistical programming. We are very happy and lucky to have you guys in our team!