AstraZeneca Secondment for Clinical Pharmacology Training

Lead Research Organisation: Cambridge University Hospitals NHS Foundation Trust
Department Name: Medicine

Abstract

This proposal will provide funding for a trainee doctor to spend 9 months working on clinical trials in the biopharmaceutical industry. Trainee doctors in the NHS are required to undertake specialist training as set out in a training curriculum. However, a number of training activities related to clinical trials are not easily accessible within an NHS setting. The biopharmaceutical industry has a wealth of experience of designing and running early phase clinical trials, so this is an ideal setting in which to undertake training.

The pharmaceutical company AstraZeneca (AZ) has offered to host a trainee doctor for a 9 month placement. This would involve working with a clinical project team to gain experience in a range of activities involved in the design, set up and running of an early phase clinical trial. The trial in question would look at the safety and effectiveness of drugs to treat increased blood pressure in the blood vessels that lead to the liver. This is often caused by liver cirrhosis. There have been no new treatments in this disease area for over 20 years and complication rates are high even with existing treatments, so this is an important trial.

In addition to providing clinical trial experience, this placement will also provide wider access to the whole development pathway for new medicines. There will also be opportunities to interact with other early career researchers through a wide range of scientific meetings and events, plus leadership and management training. In this way, the placement creates a unique opportunity for growth of the trainee's skills, knowledge and professional network which will enhance downstream career choices. In return, the trainee doctor would bring to industry specialist expertise and clinical insight gained through working within the NHS at Addenbrooke's Hospital. This will be extremely useful when designing and running the proposed clinical trial for cardiovascular and liver disease.

With their close geographical location, this placement will create a unique opportunity for AZ, the University and the NHS to work together in Cambridge to develop professional skills and talent. By encouraging transfer of staff and sharing of knowledge between different sectors, it will, in turn, promote career development for the trainee doctor. Collectively, these factors align closely with the aims of the UKRI Innovation Scholars programme bringing a range of benefits to the wider biomedical sciences sector.

Technical Summary

The aim of this secondment is to promote knowledge exchange between clinical teams in the NHS, academia and biopharmaceutical sector via cross-sector engagement on early phase clinical trial activity. This will be achieved through a 9-month secondment of a Specialty Training Registrar in Clinical Pharmacology and Therapeutics from Addenbrooke's Hospital into the clinical project team for a Phase 1 or Phase 2a study within the Cardiovascular, Renal and Metabolic group at AstraZeneca (AZ). The secondment will focus on a Phase 2 cirrhosis study with Zibotentan (an endothelin antagonist), in combination with dapagliflozin, in patients with portal hypertension or cirrhosis, an area of unmet clinical need.

The secondment will provide training for the secondee in key components of the core syllabus for Clinical Pharmacology, a discipline where there is a national skills shortage. Direct exposure to multiple aspects of the drug development pipeline will also provide a deep understanding of industry drivers in the development of a competitive molecule. In parallel, as a study physician, the secondee will bring significant research exposure, clinical acumen and a specific interest in renal disease which will be valuable to AZ in the context of renal aspects of cardiovascular and hepatic drug development.

Overall, this secondment will benefit all parties by promoting transfer of knowledge between sectors. Through direct exposure to the biopharmaceutical industry, it creates an opportunity for the secondee to enhance their professional skills, knowledge and network with opportunities for career development. By focusing on clinical pharmacology, the secondment will boost training in a specialty where there is a national skills shortage and AZ will benefit from the secondee's specialist clinical knowledge. Collectively, these factors align closely with the aims of the UKRI Innovation Scholars programme bringing a range of benefits to the wider biomedical sciences sector.

Publications

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Description SK collaboration with AZ 
Organisation AstraZeneca
Department Research and Development AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution SK contributed to the designing and setting up of the phase 2 study in the area of unmet need. Further set up a collaboration with external/ key knowledge experts within the therapeutic area to identify further knowledge gaps.
Collaborator Contribution This phase 2 study is an AZ-sponsored study. AZ provided adequate training for SK to become proficient at setting up studies
Impact This collaboration was multi-disciplinary- involving pharmacokinetics, statisticians, hepatologists and regulatory colleagues
Start Year 2021
 
Description SK secondment to AZ 
Organisation AstraZeneca
Department Research and Development AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution SK has participated (as part of an internal commercial multidisciplinary team) in setting up and monitoring a single centre, unblinded commercially sponsored. Phase 1b novel combination study of a licensed and unlicensed drug (in Phase 2 development) in healthy volunteers to assess pharmacokinetic parameters and this has progressed to moderately impaired hepatic function patients. Additionally, a commercially sponsored Phase 2b blinded RCT is being set up in a cirrhosis population.
Collaborator Contribution The commercial partner has provided a significant amount training in early phase trial activities, industry standard operating procedures, opportunities to participate in team meetings, and to be able to input into study design, formulation of inclusion/exclusion criteria utilising her own knowledge of clinical medicine combined with novel approaches to drug development.
Impact A review paper has been submitted for peer-review- which includes SK as co-author. This is a multidisciplinary effort involving scientists, pharmacokineticists, clinicians and statisticians.
Start Year 2021
 
Title SK 
Description This is a commercially sensitive area - but the drug is in early phase development for a novel indication 
Type Therapeutic Intervention - Drug
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2022
Development Status Under active development/distribution
Clinical Trial? Yes
UKCRN/ISCTN Identifier NCT05112419
Impact The study will inform future studies in well characterised groups 
 
Title Therapeutic product- a new drug combination 
Description This is commercially sensitive information- the drug is still in the early assessment phase. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2022
Development Status Under active development/distribution
Impact Targets early stages in a common condition, to delay the progression of the disease. 
URL https://clinicaltrials.gov/ct2/show/NCT04724837
 
Title ZEAL clinical trial 
Description This isa Phase 2 clincial trial in liver cirrhosis - a condition with few treatment options. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2022
Development Status Under active development/distribution
Clinical Trial? Yes
UKCRN/ISCTN Identifier NCT05516498
Impact Developed protocol for the ZEAL clinical trial. This employs the novel use of an SGLT2i (dapaglifozin) with Zibotentan. This is a two part Phase IIa/b multicentre, randomised, double-blind, placebo-controlled, parallel group dose-ranging study to assess the efficacy, safety, and tolerability of the combination of zibotentan and dapagliflozin, and dapagliflozin monotherapy versus placebo in participants with cirrhosis with features of portal hypertension. This trial has just commenced and is due to complete in Q3 2024. 
URL https://www.clinicaltrials.gov/ct2/show/NCT05516498
 
Description SK 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact SK participated in multiple internal and externally facing meetings to conceptualise, design and execute early phase trials within industry. This included numerous meetings to discuss study design. drug pharmacokinetics, pharmacodynamics, safety reporting, and study operations. She also had the opportunity to interact with Key Opinion Leaders in the subject area which allowed for the details to be dissected and discussed openly to enhance the quality of the study being designed. She also had the opportunity to interact with a Patient representative who was actively participating in the discussions about study design. This experience has given SK the broad experience of how early phase trials are designed- something she would not have had the experience of seeing in academia.

Additionally, SK has participated in large scientific meetings focussing on renal disease within the company examining new therapeutic modalities, new biomarkers and options for studying these in clinical trials of novel compounds
Year(s) Of Engagement Activity 2021,2022