Mendelian Randomization Course

The course comprises four half-days’ worth of content plus the final hackathon, and will take place over 3 weeks (plus a preliminary week 0). It consists of some on-demand pre-recorded content and some timetabled (live) content. The first day of Week 1 will be Monday 6^th November 2023. All the core content of the course is pre-recorded - live sessions are not compulsory to attend, but are supplementary to the core content. They represent a chance to engage with the course tutors. Several of the live sessions will be recorded.

Each half-day can be done whenever is convenient. A half-day of content includes three pre-recorded talks (around 20-30 minutes each) and one practical session (around 1-1.5 hour). Each of the three computer practicals should be performed individually, but there is an associated live drop-in session to come and ask questions. There is also a recorded debrief session that runs through the practical content. In terms of live content, in addition to the practical drop-in sessions, paper discussion, and hackathon, there is also a question and answer session each week to ask your questions. Questions can be asked during the week on a dedicated Slack channel, or you can ask questions live (Q+A sessions will be recorded).

The hackathon is an opportunity to perform your own Mendelian randomization investigation to use the skills you have gained during the course. This can be done individually or as part of a group.

Participants should choose one of the papers for the timetabled paper discussion (Practical 3), and one hackathon session, based on their availability and preference.

Genetics in Drug Development

The majority of biologic and small molecule drugs perturb protein targets to exert their effects. With the recent explosion in the availability of large-scale genetic association data, it is increasingly feasible to identify genetic variants that proxy the effect of perturbing a protein drug target. Leveraging such genetic data thus offers an efficient and cost-effective approach for identifying drug targets and studying their effects.

This short course “Genetics in drug development” will provide theoretical and practical advice on using genetic data to:

1. Identify drug targets
2. Investigate the effects of drug target perturbation for different indications
3. Explore potential adverse effects and repurposing potential for drug targets
4. Identify biomarkers to explore drug efficacy in early stage clinical trials
5. Identify population subgroups for which drug effects may vary
6. Explore interactions between different drugs and exposures

The course will be held online over one week and will consist of a series of recorded video lectures, live interactive sessions with practical examples, and participation in an online community that allows for interaction with peers and tutors throughout the course.

While this course is entirely self-contained, it follows on naturally from the Mendelian randomization course held in March. Participants who are interested in both topics may wish to apply for both courses.

Early phase trials are recognised to have a major impact on later phase confirmatory trials. This course presents state of the art methodology for Phase I dose-escalation studies that are delivered a mixture of lectures and practical sessions. The topics include model-based dose-escalation in-patients studies (such as Continual Reassessment Method [CRM], Bayesian logistic regression model [BLRM], Escalation with Overdose Control [EWOC]), model-free and model-assisted designs, and implementation of these designs in a software (specifically, R).

Therapies using a combination of drugs have become the mainstream approach in many therapeutic areas. They, however, require more advanced designs to establish the best dose for further study compared to single-agent trials. This course presents novel dose-finding designs for combinations and dose-schedule trials that are delivered a mixture of lectures, practical sessions, and discussion. The topics will include:

• Model-based and model-free Phase I dual-agent and dose-schedules designs;
• Phase I/II designs for molecularly targeted agents;
• Randomised dose-escalations trials;
• Inclusion of covariates into Phase I dose-escalation;

Throughout the course, the examples of implemented in practice designs will be used to demonstrate the methodology. The workshop will involve practical sessions in R on these designs implementations and discussions on the practical aspects. By the end of the course, you will design your own combination or dose-schedule trial.