Drug Discovery and Development + Clinical Trials Flashcards
Includes interactions between the Pharmaceutical Industry and Patients and Patient organizations
What is an Inclusions Criteria?
Defines the patients who have the condition (severity/type) for whom the trial is intended
And always includes confirmation that the patient freely gives their consent
(note: emergency research without consent is possible in life threatening situations)
What is an Exclusion Criteria?
- Excludes the patients who have the above condition but for whom participation in the trial would
- be unsafe (concomitant disease/treatment),
- be unethical (not on standard of care already?) or
- provide unreliable data (previous treatment could confound results / patient not likely to comply for other reasons … alcohol / drugs etc..)
What are the phases of clinical trials?
- Phase I: Approx 50-200 subjects are usually healthy but can be patients who are not expected to benefit from the investigational medical product (IMP)
- safe in humans?
- pharmacokinetics/pharmacodynamics
- might it work in patients
- Phase II: Aprrox 100-400 patients with the target disease
- is it safe in humans? same as phase I
- Phase III: Aprrox 1000-5000 patients with the target disease
- is it really safe in humans and doe it really work in patients
- does it work better than other medications for the same disease
- Phase IV: many thousands or millions of patients with the target disease
- how safe is the medication (pharmocovigilance)
- does it work in the real world
- how does it compare with similar medicines
What is a sponosr in a clinical trial?
An individual, institution, company or organization (for example, a contract research organization) that takes the responsibility to initiate, manage and/or finance the clinical trial
Who is the investigator in a clinical trial?
Individual responsible for the selection and care of subjects/patients participating in the clinical trial
What is the responsibility of the Sponsor?
- Trial design and review
- Investigator selection
- Training of the Investigator/Site staff
- Funding of the trial (it can be very expensive!)
- payments for site/volunteer participation (patients are never paid except out of pocket expenses, unlike health volunteers)
- providing trial insurance/enabling compensation of subjects for research associated injury
- Investigational product supply
- All approvals for the start and continuing conduct of the trial
- Providing safety information to the investigators to enable patient management and reporting adverse drug reactions (SUSARs) to regulatory authorities
- Monitoring each participating site
- protocol compliance
- accuracy of data collection / no fraud
- Trial analysis and reporting of results
What should be involved in a protocol?
- The need for the trial including a rationale for the therapy being investigated (and any proposed comparison)
- Compliance with Declaration of Helsinki
- The subject type (eg HV or patient) and eligibility criteria (inclusion and exclusion criteria)
- The outcomes to be assessed to meet the trial objective (both efficacy and safety)
- The data to be collected to enable these outcomes to be assessed
- The sample size required to meet the trial objective (superiority, non inferiority, equivalence etc)
- Stopping rules – for individual subject and/or cohort and/or trial
- Instructions for management of adverse effects (if appropriate) and for reporting safety data to the regulatory authority and ethics committees
- Planned analysis of trial data including any interim analysis (futility/efficacy/safety)
- Publication plan
What is the responsibility of Investigators in clinical trials?
- The Investigator must be suitably qualified to assume responsibility for the trial at the site
- Must be familiar with the Investigational Product (IP)
- Responsible for submitting the protocol to and communicating with the independent ethics committee prior to and as relevant data arise during the study
- Recruiting subjects in compliance with the eligibility criteria defined in the trial protocol
- Obtaining written informed consent from trial participants prior to starting trial treatment(s)
- Ensuring training of site staff on the protocol requirements and patient care needs
- Ensuring accurate recording of data collected for the study
- Compliant reporting of any adverse drug reactions to the sponsor according to regulatory requirements
- Ensuring compliance with Good Clinical Practice (GCP requirements) including permitting monitoring of trial data reported on the case report form, and facilitating audits and inspections as required to validate trial information
- Keep records of patient participation and progress in the trial for required periods post study completion
- Some responsibilities can be delegated to an appropriately trained person ( e.g. qualified study nurse or research physician)
- completing the case report forms
- bloods for safety tests
- conducting physical examinations as required
- Overall responsibility for the conduct of the trial at the site (and of any site staff to whom tasks are delegated) remains with the investigator
What are endpoints in a clinical trial?
-
Safety and tolerability: Adverse events regardless of drug causality, specific laboratory tests, liver functions
- Biomarker: a biological characteristic that is objectively measured and evaluated as an indicator of - normal biological processes, pathogenic processes, or pharmacologic response to a therapeutic intervention
- Surrogate: a biomarker which is accepted by the regulatory agencies to correlate to a meaningful clinical outcome
- Efficacy: Disease outcome, surrogate endpoint/biomarker
- Mortality/morbidity endpoints:
What is the EU Clinical Trials Directive 2001/ 20/EC
- Framework which sets out how a clinical trial investigating the safety or efficacy of a medicinal product in humans must be conducted
- Provides greater protection to participants
- Ensures quality of conduct
- Harmonise regulation and conduct of clinical trials in Europe
What are patient organisations?
Patient organisations (sometimes also called patient groups or patient associations) advocate on behalf of patients, often in a particular disease area. They may fund medical research and/or provide information and support for patients and their families and carers and/or influence health policy on behalf of patients.
What are expert patients?
Expert patients are patients who are skilled and knowledgeable in the management of their disease.
Some patients also develop expertise in understanding medicines research and development, clinical trials and the regulatory process.
What is the Patient Engagement Quality Guidance?
A practical guide to planning, developing and assessing the quality of patient engagement (PE) activities and projects throughout the development and lifecycle of medicines.
What is the EUPATI and what are it’s objectives?
European Patients’ Academy on Therapeutic Innovation
- Develop and disseminate objective, credible, correct and up-to-date public knowledge about medicines R&D
- Build competencies & expert capacity among patients & the public
- Facilitate patient involvement in R&D to collaborate in academic research, industry research, regulatory and HTA authorities and ethics committees
What is the role of the NAtional Institute for Health Research (NIHR)
NIHR provides a standardised, industry-wide approach to engaging patients earlier in the clinical development process and instils a culture of partnership working between the pharmaceutical industry and patient organisations.
