Guest writer Thomas Zwingers part II- Ask the Experts: Late Phase Oncology Trial Design

Prinicipal Biostatistician Thomas Zwingers hosted Part II of his German-language webinar "Statistical Considerations in Oncology". Part II focuses on statistical methods for early decisions in Phases II and III.

 

According to expert biostatistician Thomas Zwingers, how can adaptive trial design be a method for the future of cancer research? 

 

During Phase III development, efficacy of the drug should be confirmed. Many new products have to find a very specific mechanism of effectiveness, so therefore subpopulations are necessary. Flexible study designs that allow for early termination and the use of fewer patients can be a successful solution for determining clinical efficacy. In oncology trials, we need to take into consideration differentiating factors such as slow patient recruitment, the importance of patient genotype, the use of various treatment combinations and the fact that the primary endpoint is overall survival time or time to progression. 

 

Adaptive Designs in late phase cancer research offer the possibility to make modifications to a study while in progress on the basis of new information pulled from accumulated data. While it is well know that there is the possibility to re-estimate the number of patients needed for a study based on observational data in interim analysis, it is less known that design can allow objectives to be achieved in one study that would normally require the scheduling of two distinct studies, so called "seamless Phase II/III designs".

 

Seamless Phase II/III designs combine two sequential and separate studies into one study and allows the use of collected information in the first stage to adapt the design in the second stage. The advantages of in this design are a reduction in overall time in the development of a drug, fewer patients required, and the early availability of long-term safety data. 

 

Another interesting possibility of an adaptive design is to select the right target population for the drug. This is of special interest in the development of highly specific cancer drugs, which are only effective in selected patient populations - for example, monoclonal antibodies. An adaptive study in Phase II/III may allow for the selection of the most promising target population in the first stage for the second stage.

 

Based on CROS NT's experience in oncology trials, their expert biostatisticians recommend the following for late phase adaptive trials:

- Budget more time for planning of an adaptive design as compared to a standard design
- Interact with regulatory authorities in the planning phase especially for Phase II/III studies
- Use simulations to calculate the power of the sample size and the probability of success
- Evaluate whether or not to stop the recruitment of patients for the interim analyses
- Schedule frequent monitoring visits in order to provide as much data as possible for the interim analyses

About Thomas Zwingers

In Thomas' current role, he provides pharmaceutical, biotechnology and medical device companies with statistical methodology advice pertaining to trial design, conduct and reporting including regulatory submissions. Thomas has been working in the clinical trial environment since 1980 in project team management and statistical analysis. He has particular expertise in Adaptive Designs and Bayesian Framework, Meta-Analysis and Non-Inferiority trials with therapeutic expertise in Oncology, Respiratory and Dermatology.

How to Tackle the Most Common Interview Questions (that you will get asked!)

Interviews are nerve-wracking enough, so make them a bit easier on yourself and go in prepared with unique answers to the most commonly answered questions.

Kubo Recruitment has put together a handy list of the most common questions and some helpful tips on how to best answer them.

1. "Tell me about yourself." 

While this is a very open-ended question, it does not give you free rein to tell the interviewer everything, including what you did over the weekend or the current status of your relationship. This is a chance for you to show the employer your personality, so they can see if you fit in to the company culture. Give the employer a brief history of your professional and academic accomplishments to give them an idea of how you got to the point where you are today. You can show the employer hints of your personality in your response by discussing your hobbies as well - like your passion for travel or sport. It's ok to have fun with your answer, but keep it professional.

2. "Why did you leave your last job?"

Number one rule: be honest. If you were laid off or fired, explain why, but always show that you have gained knowledge and growth from your previous role. No matter your response, demonstrate that the job you are interviewing for would be a stepping stone in your career. DO NOT bad mouth your previous employer, as it comes across as childish and unprofessional.

3. "Why did you apply for this job?" 

Similar to question 1, show that you have read up on the job role. Pick out points of the job description that suit you perfectly and explain why by giving examples. Focus on what you can offer the company in terms of skill set and personality traits. Point out positive aspects of the company you are applying to as well; for example mention that you would like to be part of a great work environment or a successful company. Show that you are not only passionate about the job role, but about the company you hope to join.

4. "Where do you see yourself in 5 years?"

Avoid discussing your personal plans when this question comes up. The employer is usually trying to find out if you're going to be a "flight risk" - e.g. are you someone who changes companies every 2 years, do you have trouble settling down, are you planning on starting a family in the near future? Be passionate and realistic about your answer. Demonstrate that you have the intention to grow in your field, but that you are also flexible and adaptable to change. 

5. "What are your weaknesses?" 

This question feels like a trap, doesn't it? Never say that you don't have any. It's simply not true, no one is perfect. Turn a negative into a positive - for example: point out that you are meticulous to detail or that sometimes you find it better to work individually. These are weaknesses that reflect more on your personality rather than your work ethic.

6. "Do you have any questions?" 

Always prepare some questions beforehand by looking at the company's website. Questions show you are interested in the role and the company. Bring up any questions or doubts you may have, but avoid asking about salary until the employer brings it up first. This is the time to show the employer you are genuinely interested in the job role. 

The most important aspect of interviewing you can bring to the table is confidence. Having confidence in yourself shows the employer you'll have confidence in the work you do as well.