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MSc Experimental Medicine (Cancer)
MRes Experimental Medicine (Cancer)
This course will enable you to work within a leading Phase 1 cancer clinical trials unit.

MRes Experimental Medicine (Cancer)

Year of entry: 2018

Course unit details:
Assembling pre-clinical and early clinical development strategies for a new candidate drug

Unit code MEDN66212
Credit rating 15
Unit level FHEQ level 7 – master's degree or fourth year of an integrated master's degree
Teaching period(s) Semester 2
Offered by Division of Cancer Sciences
Available as a free choice unit? No

Overview

 

The purpose of this module is to provide a foundation and appreciation of what has to be considered in planning and designing the pre-clinical and early clinical strategy for a new candidate drug. A wide range of issues has to be considered before a drug is dosed in man. Amongst these is whether the pre-clinical toxicity supports entry into man, and if so, whether the first in man study should be performed in patients or healthy volunteers and what the initial starting dose should be, escalation dose increments and setting an upper dose limit?. A basic understanding of drug handling will also be provided, along with the pre-clinical pharmacokinetic and pharmaceutical development packages required to support an application to the regulatory authorities to gain approval to dose the drug in man. Key objectives of any early clinical development programme are the determination of (a) drug exposure- pharmacokinetics (b) drug safety (c) drug effect- pharmacodynamics and clinical efficacy. Understanding these three elements is critical if clear go/no-go criteria for progression of the drug into further clinical development are to be put in place and adhered to.

 

This unit will cover the following indicative content:

  • An introduction to drug manufacture, formulation development, stability testing of the pharmaceutical product
  • Pre-clinical pharmacology and toxicological studies pivotal to the design of the first in human experiment
  • Basic pharmacokinetic parameters
  • Understand the regulations surrounding first-in-human studies from the Expert Scientific Committee report from the TeGenero incident
  • Inform students on how to conduct a site audit to appraise the feasibility of a clinical trials unit to conduct the 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 trial
  • Using real datasets to determine whether specific drugs should/should not progress into further clinical testing

Aims

 

This unit aims to:

 

 

  • Understand the safety, pharmacology and drug disposition data in animals which is required prior to commencing human clinical trials
  • Understand the pharmaceutical manufacturing issues which need to be addressed to ensure the quality of the pharmaceutical product for human administration
  • Understand the requirement for and basic design of pre-clinical safety studies required to assist clinicians in determining the likely range of safe exposures to the candidate drug, and the possible consequences if these doses are exceeded
  • Provide practical guidance to balance the importance of a range of pre-clinical toxicities to safely entering man. If considered suitable for clinical testing, students will calculate the safe starting dose, dose increments and determine criteria for ceasing dose escalation
  • Experience the platform of evidence data required to justify progressing a compound forward for further development incurring the significant resource and human exposure implications of the decision or whether to cease drug development
  • Provide basic design considerations for first in human administration designs along with how to determine early tolerability, pharmacokinetics and efficacy of a candidate drug in the clinic
  • 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

 

Knowledge and understanding

LO1: Understand the pre-clinical package of information to support a MHRA application

LO2: Explain basic pharmacokinetic parameters and how these relate to safety and efficacy implications.

LO3: Discuss issues surrounding whether or not to progress a drug into further development

LO4: Appreciate data which is derived from each phase of clinical development

LO5: Discuss the challenges in setting a safe starting dose

LO6: Understand the role of quality manufacturing systems underpinning the pharmaceutical product

LO7: Discuss and understand concepts for alternative designs of first-in-human trials

Intellectual skills

LO8: Identify the key data which governs whether  a new drug should/should not progress into further clinical testing

LO9 Balance findings revealed during an audit of a clinical trials unit to inform the decision whether or not to place a clinical study

LO10: Critically review a the recommendations from the Expert Scientifc committee report into the TeGenero incident and discuss the relevance to cancer trials

LO11: Apply pharmacokinetic knowledge to dose setting decisions

LO12: Design approaches and queries to retrieve data

Practical skills

LO13: Perform and communicate how to assemble a pre-clinical strategy to support entry of a drug into man

LO14: Construct a concentration-time plot and derive basic pharmacokinetic parameters

Transferable skills and personal qualities

LO16: Work collaboratively within a team

LO17: Present ideas and work in a verbal and written format

LO18: Understand about resource allocation and project planning

LO19: 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 ~20x 0.5-1.5h lectures over 2 weeks, and ~7 x 1.5--5h workshops. The workshops will allow the students (as groups) to actively participate in the different stages of pre-clinical and clinical development. The first will ask each student to individually prepare a proposal for a pre-clinical development package of a compound based on early physiochemical data and initial concepts for clinical testing. Students will be provided with a number of pre-clinical tests which can be conducted to support entry into man (and a limited budget which will not support conducting all tests) and will be required to prioritise those tests most informative to support the proposed clinical plan. In preparation for the second workshop, students will be provided with the Duff report from the TeGenero incident and each student will be allocated to defend the actions of one of the stakeholder groups. During the third 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 fourth 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. For the fifth workshop, students will be presented with data from the early clinical studies for several drugs and be asked to justify their rationale as to whether to continue or discontinue the drug from further development.  A sixth 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. The seventh workshop will introduce students to the principles of human pharmacokinetics

.

Employability skills

Analytical skills
through data interpretation and literature review
Group/team working
through delivering research project 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

Assessment methods

Method Weight
Written assignment (inc essay) 33%
Report 34%
Set exercise 33%

Feedback methods

Feedback to students will be made through Turnitin.

 

Study hours

Scheduled activity hours
Lectures 50
Independent study hours
Independent study 100

Teaching staff

Staff member Role
Andrew Hughes Unit coordinator

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