Clinical pharmacology scientist

KSBs

Knowledge

K1: Theoretical principles of drug action- How drugs interact with their targets, including drug-receptor theory and mechanisms of action – The principles pharmacokinetics (including Absorption Distribution Metabolism and Excretion), toxicokinetics and pharmacodynamics and their inter-relationship- The principles of toxicology, their application in safety assessment and in determination of the therapeutic index (the balance of safety versus efficacy in relation to dose)• How a drug’s formulation and characteristics (e.g. bioavailability, permeability, solubility, formulation, gastrointestinal pH, prandial state) can affect how it performs in the body and impact upon dose selection Back to Duty

K2: Dose determination- The principles of pre-clinical safety testing, determination of safety margins and how they affect selection of appropriate clinical dose levels – The principles of using pre-clinical data to predict both human Pharmacokinectic/Pharmacodynamic (PKPD) and determine the appropriate dose- The principles of starting dose calculation and trial progression (including dose escalation) Back to Duty

K3: Study design and delivery- The types of pharmacology studies that are required/optional and whether to include and conduct them- How the following impact upon on dose selection, study design and outcomes: a) Drug-drug interactionb) Organ impairmentc) Aged) Intrinsic factors (e.g. population)e) Extrinsic factors (e.g. food)- Pharmacology-related stopping criteria employed in the early phase studies- How to evaluate, monitor and address relevant risks to study delivery- The principles of risk-benefit analysis in relation to patient management- Standard, adaptive and other novel study designs, when to use them and the associated risks- The impact of immunogenicity on the PKPD of biotherapeutics- Optimisation of sampling timepoints- Trial progression strategies and how to use them appropriately (e.g. dose escalation)- Common types of protocol deviations that confound study results, impact the interpretation of results and may put subjects at undue risk- The principles of go-no-go decision matrices- The resource associated with clinical pharmacology studies (e.g. cost, timeframes) Back to Duty

K4: Study reporting and documentation- Content and generation of study documents (design synopsis, protocol, study report synopsis, clinical study report)- Reporting guidelines and best practice for documenting data, analysis processes and archiving to ensure reproducible results- Common types of protocol deviation that can impact on results and data interpretation Back to Duty

K5: The appropriate use of statistics- Essential statistical principles and tests used in the life sciences (e.g. sample size, power calculations) and in the design of clinical trials- Statistical concepts and tools for data analysis and data interpretation in different situations (e.g. big data, sparse data, missing data)- The principles of powering, estimation and modelling approaches including when to apply them to a particular study Back to Duty

K6: Analysis and interpretation- The role of data visualisation, summarisation and analysis – The role of an analysis plan and its component parts – The principles, limitations and appropriate application of various standard quantitative techniques (e.g. non-compartmental analysis, population modelling, physiologically based pharmacokinetic modelling)- The scope and capabilities of both typical and innovative bioanalytical techniques used for endpoint analysis- Methods of data research, review and synthesis Back to Duty

K7: Legal and regulatory principles- The principles of Good Clinical Practice (GCP), Good Manufacturing Practice (GMP), Good Laboratory Practice (GLP) and Good Documentation Practice (GDocP) – Laws and relevant regulatory/guidance documents, including regional differences where appropriate- Regulatory processes and review cycle timelines- Licencing requirements- The clinical pharmacology content in drug labelling – The clinical pharmacology components of the marketing application – Data protection and confidentiality requirements when preparing materials (e.g. redaction, re-labelling and referencing public domain case studies)- The principles of quality control, quality assurance and report processes- The principles of ethical business practice and relevant codes of conduct- The principles of research ethics and application to clinical trials and how these may differ for vulnerable populations (e.g. paediatrics, elderly) Back to Duty

K8: The interconnected role of the clinical pharmacology scientist- The impact of clinical pharmacology on key decision points during drug development, and the information required to enable informed decisions- The environments in which clinical pharmacology scientists work- The other roles/stakeholders/bodies that interact with clinical pharmacologists and the exchanges that will need to be conducted – The impact of clinical pharmacology on the success of the project (e.g. scientific validity, commercial, key risk areas) Back to Duty

K9: Drug discovery and development- The stages of drug discovery and development- The principles of preclinical to clinical translation, translational research and experimental medicine. To include how biomarkers relate to disease processes and drug mechanism of action, and can be related to clinical safety and efficacy endpoints- The principles of reduction, refinement and replacement in the use of animals in research- How the principles of clinical pharmacology apply to new therapeutic approaches (e.g. cell-based therapies, antibody-drug conjugates, oncolytic viruses, Ribonucleic Acids (RNAs)- The principles of pharmacogenomics and impact on drug development- Innovative drug delivery and formulations Back to Duty

K10: Learning and development- The principles of learning and developing in the workplace, including ethical and safe practices with regards to coaching and mentoring (e.g. appropriate interactions, confidentiality)- The principles of, and good practice relating to, equality and diversity in the workplace- An awareness of relevant workplace leadership strategies and skills, including matrix leadership and change management in a scientific organisation Back to Duty

K11: Effective communication- How to assess the needs of stakeholders and tailor effective written and verbal communications to them- The scope and impact of different communication methods Back to Duty

Skills

S1: Dose determination- Calculate safe and efficacious human dose predictions (amount and schedule) from pharmacokinetic and toxicokinetics pre-clinical data using quantitative pharmacology methods (e.g. by allometry or physiologically based modelling)- Calculate recommended safe dose for first administration to humans based on pre-clinical data – Make predictions regarding viability/safety of additional dose levels and the likelihood of the effectiveness of a dose reduction strategy relative to maintaining and appropriate therapeutic window – Make recommendations about appropriate trial progression strategies (e.g. dose escalation)- Select and interpret data from a range of relevant sources (e.g. in silico models, biochemistry tests) in order to determine suitable doses for specific populations Back to Duty

S2: Study design and delivery- Perform robust data reviews, including appropriate extrapolation from available knowledge and data, and the use of appropriate techniques to determine the potential for clinically relevant drug-drug interactions – Design efficient, safe, scientifically robust and feasible study protocols and support the design of bespoke clinical pharmacology development plans. Design should consider preclinical data and the impact of external factors (e.g. characteristics of the drug, budgetary, competitive landscape) and use appropriate powering, estimation, modelling and adaptive approaches where applicable.- Optimise study assessments (e.g. the type and timing of pharmacokinetic sampling, biomarkers and other assessments) taking into account both study needs and subject well-being, and including appropriate assessment criteria (e.g. interim and final) for analysis – Consider and propose methods (e.g. physiologically based pharmacokinetic modelling) alternative to clinical studies when appropriate- Contribute to the design and execution of go-no-go decisions Back to Duty

S3: Study reporting and documentation- Write flexible and robust protocols- Make relevant contributions to clinical study reports- Interpret data and contextualise results (Interim and Final) Back to Duty

S4: The appropriate use of statistics- Interpret statistical results appropriately (e.g. when summarising study outcomes)- Use appropriate software and graphical exploration to perform data analysis (e.g. exposure response, exposure safety)- Apply appropriate statistical techniques when analysing and summarising study outcomes, with support from statisticians where necessary Back to Duty

S5: Interpretation of clinical study results- Contribute to analysis plans that describe how data will be analysed, summarised and graphically displayed- Select and apply the most appropriate method of data visualisation and analysis- Interpret data during study delivery for any interim decision points and for final study reporting discussions and conclusions;- Interpret the collated output from across multiple clinical studies Back to Duty

S6: Critical evaluation and decision making- Contextualise results based on other internal and external information- Demonstrate aptitude in integrating information from a range of sources and critically evaluate it- Identify potential gaps in the clinical pharmacology understanding of a new molecular or biological entity- Identify the implications and making appropriate decisions (e.g. about study design and timing) Back to Duty

S7: Legal and regulatory principles- Complete the required clinical pharmacology components of clinical trial application and a licensing application- Contribute to writing the drug label – Develop and write relevant components of regulatory documents (e.g. investigator brochure, protocol, informed consent document)- Interpret questions and feedback from regulatory, ethics and other review bodies and formulate appropriately detailed and clear responses- Data protection and confidentiality requirements and avoid breaches Back to Duty

S8: Effective communication- Communicate effectively about their work and/or the work of their team to specialist and non-specialist audiences (e.g. oral presentation, protocols, consent forms and scientific reports)- Write scientific and technical documents that clearly convey interpretation and impact of findings – Discuss work constructively and objectively with internal and external stakeholders Back to Duty

S9: Study management- Assess risks to delivering a protocol for the clinical pharmacology package and formulate mitigation plans- Redact, relabel and reference public domain case studies to avoid confidentiality breaches Back to Duty

S10: Learning and development- Research, critique and assess new techniques and methodologies – Listen to learners to assess their understanding and adapt techniques to their needs, using ethical and safe practices when mentoring, coaching and training others Back to Duty

Behaviours

B1: Integrity and Reliability: The ability to work with integrity, showing respect for the confidentiality of information, taking responsibility for actions and with an intrinsic ethical stance to all aspects of day-to-day activities, ensuring actions are in the best interest of stakeholders. Work using the principles of the scientific method and with a concern for maximising the scientific value of a study or dataset Back to Duty

B2: Flexibility and Adaptability: A professional approach, no matter what challenges emerge. A willingness to consider the broader context of project and stakeholder needs. A willingness to engage with innovative practices and make suggestions for improvements. An ability to adjust to, function and flourish in a diverse environment. Back to Duty

B3: Team Working: The ability to lead group activities to arrive at a common goal. The ability to listen to a wide range of views and be inclusive when seeking input. An ability to work in a team, demonstrating respect for colleagues and the viewpoints of others. A willingness to share knowledge and expertise with others. The ability to maintain effective working relationships and collaborations. Back to Duty

B4: Advise and support: The ability to address comments or questions by drawing upon clinical pharmacology expertise and the application of broader principles and knowledge. The ability to identify uncertainties when making decisions and to highlight these, including any assumptions and limitations. An awareness of limits of knowledge and competence, operating within those limits. Back to Duty

B5: “Patients First” Attitude: Puts the patient first and respects their contribution by ensuring they are fully informed, and their views inform decision making processes Back to Duty

B6: Planning, Prioritisation and Organisation: Effective time management, organisation, and appropriate prioritisation, setting projects in the wider context and fiscal environment. Takes the initiative, working independently and coordinating effectively with others to deliver. Back to Duty

B7: Continuing Professional Development (CPD): Recognition of the importance of CPD and a commitment to lifelong learning in personal development and the support of others. Demonstrates curiosity, keeps up to date with relevant developments and proactively develops knowledge to ensure that scientific and business decisions are based on strong science. Back to Duty