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MRes Experimental Medicine (Cancer) / Course details

Year of entry: 2020

Course unit details:
Early Clinical Cancer Drug Development

Unit code MEDN66222
Credit rating 15
Unit level FHEQ level 7 – master's degree or fourth year of an integrated master's degree
Teaching period(s) Summer semester
Offered by Division of Cancer Sciences
Available as a free choice unit? No

Overview

 

The purpose of this module is to provide a framework to consider how to optimise the chances of success in the early clinical testing of a novel cancer drug. Despite having a potentially wonderful drug, testing it in the wrong tumour type, or at the wrong schedule or dose; or with the wrong combination of agent- could terminate an otherwise promising drug. Students will gain a foundation for considering what pre-clinical experiments can be done to inform on the optimal options for clinical testing. Students will experience real-life scenarios to the practice of translational medicine within the drug development environment, addressing three common, yet critical scenarios, to ensure a successful transition of the drug into early clinical testing

  • Should the drug enter clinical testing?
  • What pre-clinical data will inform the optimal design thus success of the early clinical plan?
  • How can a first in man study deliver the triad objectives of safety, efficacy and pharmacokinetics?

 

This unit will cover the following indicative content:

  • An introduction to how pre-clinical experimentation can inform on the preferred clinical trial to maximise the success for a new anti-cancer drug.
  • Understand constraints to the application of novel technologies into clinical testing- both from a cost and logistical perspective
  • Understand the types of biomarkers; and notably how pharmacodynamics biomarkers can inform dose and schedule and how predictive biomarkers can inform tumour type and combination
  • Inform students on how to conduct a site audit to appraise the feasibility of a clinical trials unit to conduct the cancer study according to protocol
  • Interpretation of tolerability data from an ascending dose Phase 1 trial in cancer patients, simulating a real-life dose escalation meeting
  • Plot and interpret a pharmacokinetic drug concentration-time data from a Phase 1 cancer trial
  • Understand the steps required to qualify and validate a biomarker to either a clinical decision making biomarker or an exploratory endpoint in a clinical study
  • Understand the different phases of clinical drug development and the studies that go into these phases, including what can be assessed from them, as well as more important what cannot
  • Provide students real-life experience of sitting on a governance body to decide whether or not to progress a pre-clinical drug into clinical testing and if so- how to mitigate for the pre-clinical toxicity signals

Aims

 

The unit aims to:

  • Understand how a good drug can fail due to the choice of the wrong tumour setting, combination, schedule, dose or patient population to conduct the initial clinical trial
  • Demonstrate how pre-clinical experiments can be conducted to inform the choice of schedule, combination, dose, tumour or patient type and thus optimise the chance of a good drug revealing itself
  • Explore pharmacodynamics biomarkers of the hallmarks of cancer, which can be measured early in the programme to demonstrate unequivocal evidence of biological activity
  • Understand the weight of evidence which needs to be assembled before a pharmacodynamics biomarker can be used as a surrogate endpoint; and before a predictive biomarker can be used as a companion diagnostic
  • Understand how the fundamental triad objectives of safety, efficacy and pharmacokinetics can be derived and interpreted from Phase 1 clinical studies
  • Determine the most valuable pieces of pre-clinical data which inform the design of a first in human clinical trial
  • Provide opportunity for students to learn the critical skill of site selection- to enhance the chance of a successful first-in-man study; assembling a site audit programme and then utilise this in a site visit to two first-in-human units to consider their suitability as a site
  • Provide understanding of basic pharmacokinetic parameters

 

Learning outcomes

 

 

 

Category of outcome

Students should/will (please delete as appropriate) be able to:

Knowledge and understanding

LO1: Understand the key design challenges for a first in human experiment which can conspire against a good drug revealing itself

LO2: Explain the types of biomarkers and their application to drug development

LO3: Understand the steps required to qualify and validate biomarkers

LO4: Appreciate available pharmacodynamics biomarkers to demonstrate biological activity against the hallmarks of cancer

LO5: Understand how to interpret pre-clinical toxicological data to inform the safety design of the first-in-human study

LO6: Level of evidence required to credential a putative target as meritous of clinical testing

LO7: Understand the research landscape for conducting experimental cancer medicine studiesi

Intellectual skills

LO8 Balance findings revealed during an audit of a clinical trials unit to inform the decision whether or not to place a clinical study

LO9 Develop and communicate a strategy to recommend whether a dose escalation should/should not proceed in a first-in-human clinical trial

LO10: Critically review which pre-clinical translational experiments most inform the clinical plan in a resource constrained environment

LO11: Apply the framework of biomarker qualification to prioritise putative pharmacodynamics biomarkers from literature review

Practical skills

LO12: Construct a concentration-time plot and derive basic pharmacokinetic parameters

LO13: Construct a schedule of assessments from a protocol synopsis

Transferable skills and personal qualities

LO14: Work collaboratively within a team

LO15: Present ideas and work in a verbal and written format

LO16: Understand about resource allocation and project planning

LO17: Work through the problem-solving cycle

 

Teaching and learning methods

 

This unit will delivered in a blended format combining face-to-face lectures and open discussions to introduce concrete examples and encourage attendees to draw upon their own reading and experience.  Group, problem based learning will show a deeper understanding of the area and encourage collaborative working.  Example case-studies will be drawn from real, anonymised datasets from first in human studies and drug development programmes.  The F2F teaching will be delivered as ~28x 0.5-1.5h lectures over 2 weeks, and ~4 workshops. The workshops will allow the students (as groups) to actively participate in the different stages of pre-clinical and clinical development. In the first workshop students will learn how to appraise a new potential clinical trial protocol and deem whether it is of scientific merit and feasible and identify key risks and mitigation strategies to delivery. The second workshop, data from a dose escalation cohort will be presented and discussed, simulating real-time dose escalation meetings. The limitations of differing definitions for “Dose limiting toxicity” will be demonstrated. The third workshop with introduce students to methods of plotting and interpreting a concentration-time profile on a semi-log plot, with calculation of basic PK parameters which can be used to calculate a loading dose and dosing interval. A fourth workshop will consider what comprises a good phase I unit and features to audit- followed by a visit to 2 of the Manchester CRF’s to determine their suitability for conducting first in human studies.

Employability skills

Analytical skills
through data intepretation and literature review
Group/team working
through delivering research projects to dissertation standards
Innovation/creativity
through designing a plan for clinical research projects
Leadership
taking ownership for defining, delivering, interpreting then communicating research
Project management
of two research projects- RP1 and RP2 at 60 credits each
Oral communication
by summative course assessments
Problem solving
through engagement with patients cancer disease
Research
the fundamental basis of the year programme
Written communication
by summative course assessments
Other
through awareness and engagement with life skills courses at Manchester library taught in module 2

Assessment methods

Method Weight
Written assignment (inc essay) 83%
Oral assessment/presentation 17%

Feedback methods

The students will receive feedback on their work through Turnitin.

Student feedback is the central aspect of how the programmes are organised and developed. Feedback mechanisms include the following:

      I.        Student representation from each year of the programmes on the MRes in Experimental Cancer Medicine Programme Committee

    II.        Online feedback questionnaire on which students rate the quality of teaching in terms of delivery, handouts, presentation etc.

Study hours

Scheduled activity hours
Lectures 50
Independent study hours
Independent study 100

Teaching staff

Staff member Role
Louise Carter Unit coordinator

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