General Flashcards
Who does GCP apply to?
Only technically applies to CTIMPs = with drugs
CTIMP = Clinical trial of investigational medicinal products
Who provides GCP training?
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)
What can CTIMPS be testing?
Efficacy
Safety
Absorption, distribution, metabolism, excretion
Who regulates CTIMPs
Medicines and Healthcare products Regulatory Agency (MHRA)
What guides Non-CTIMPS?
UK Policy Framework for Health and Social care Research
Describe the following roles of sponsor, CI and PI
Sponsor
Initiation, management and financing of study
Ensure insurance, approvals and registrations in place
Can be an organisation
Retains overall responsibility
May outsource functions to CI, contact research organisation (CRO) or clinical Trials Unit (CTU)
Chief Investigator
Responsibile for conduct of study
Management and oversite
Extensive and found in UK Policy Framework for Helth adn Social Care
Principal Investigator
At site, takes responsibility for initiation anf conduct e.g recruitment,
Make a delegation of futies log - who is doing what and are they competent?
Mainatian recordds
Where to go for CTIMP ethical approval?
Health Research Authority, part of DoH.
MHRA also
What does the HRA do?
protect and promote interest of patients and public, provide national governance system
Governance of health research
Decision tool to tell you if ou need approval from NHS research ethics committee
(REC).
Check compliance with legislation, exit strategy, funding, insurance.
What is a REC used for?
REC needed for almost all research. Also for change of protocolos
What does a site file keep?
Site file keeps all neccessary doccuments
Delegation of duties and/or authorisation logs
What safety issues are recorded?
Safety of individual prevail over science and society
Safety monitioring needed of everything that happens to a participant
Anything that MAY have been caused
Also serious or unintended consequences
Explain some of the principles of GCP
1.Clinical trials should be conducted in accordance with the ethical principles that have their
origin in the Declaration of Helsinki, and that are consistent with GCP and the applicable
regulatory requirement(s).
2. Before a trial is initiated, foreseeable risks and inconveniences should be weighed against
the anticipated benefit for the individual trial subject and society. A trial should be initiated
and continued only if the anticipated benefits justify the risks.
3. The rights, safety, and well-being of the trial subjects are the most important considerations
and should prevail over interests of science and society.
4. The available nonclinical and clinical information on an investigational product should be
adequate to support the proposed clinical trial.
5. Clinical trials should be scientifically sound, and described in a clear, detailed protocol.
6. A trial should be conducted in compliance with the protocol that has received prior
institutional review board (IRB)/independent ethics committee (IEC) approval/favourable
opinion.
7. The medical care given to, and medical decisions made on behalf of, subjects should always
be the responsibility of a qualified physician or, when appropriate, of a qualified dentist.
8. Each individual involved in conducting a trial should be qualified by education, training, and
experience to perform his or her respective task(s).
9. Freely given informed consent should be obtained from every subject prior to clinical trial
participation.
10. All clinical trial information should be recorded, handled, and stored in a way that allows its
accurate reporting, interpretation and verification.
11. The confidentiality of records that could identify subjects should be protected, respecting
the privacy and confidentiality rules in accordance with the applicable regulatory
requirement(s).
12. Investigational products should be manufactured, handled, and stored in accordance with
applicable good manufacturing practice (GMP). They should be used in accordance with the
approved protocol.
13. Systems with procedures that assure the quality of every aspect of the trial should be
implemented.
14. Provision has been made for insurance or indemnity to cover the liability of the Investigator
and Sponsor, which may arise in relation to the clinical trial
What guides CTIMPS
GCP
UK Policy Framework for Health and Social care Research 2017
Medicines for Human Use (Clinical Trials) Regulations 2004
Give some principles of consent
Need a patient information sheet approved by research ethics committee
Is a process
Receive not take
Person taking consent should be part of medical team
Within Integrated research application system IRAS, if data is accessed without consent outside of the clinical team then a confidentiality advisory group (CAG) may be required.
Willingness to participate should be continually checked throughout the study
What is source data? What is sent to sponsor?
Source data (original form) gets transcribed to case report forms to send to sponsor.
How does sponsor insure quality of data control?
Sponser appoints monitor at each site who ensures quality – performs source data vertification
What if protocol is not adhered to?
Need to keep a study deviation log- when protocol is not adhererd to or diaviated form
What is a serious breach of the study protocol?
likely to effect significatly:
Safety or physicla or mental integritiy of subjects or
Scientific value of the study
What should happen if there is a serious breech?
Reported to REC
What is a Serious adverse event?
Result in: Death Life threatening Hospitalisation disability or incapacity (persistent Congenital abnormality/birth defect
Is it attributable to intervention
How do you know if adverse event is unintended or not?
Look at the Investigator Brochure, provided by sponsor, all known clinical info about non-licenced medicine
Summary of product characteristics, as above but if licenced
Then, expected or unexpected according to reference safety info (RSI), in protocol
What is a likelihood ratio
Independent of prevelance
Single figure from sensitivity and specificity
LR = how many times more (or less) likely a positive test result is ti be found in disease vs non diseased
Positive = Probability of having disease with a positive test result
Negative = probability of having disease with a negative test result. (so want to be low)
So both you take probablity of (either +ve or -ve) with disease/ probability without disease
Postiive = sensitivity/ (1-specificity)
Sensitivity = % true positive Specificity = % true negative 1-Specificity = % false postive
Neative =false negative/ true negative
=1-sensiitvity/ Specificity
Therefore
Postivie liklihood ratio = probability of true positive/ false positive
What is a meaningful likelihood ratio result
For positive (ruling in disease) then >1 For negative (ruling out disease) then <1
What is pretest probablility
Be subjective or objective.
Can use prevelence of disease in age group
How to work out pretest odds vs pretest probability
Pretest prob/ 1-Pretest prob (chances you do/ chances you dont)
Posttest odds?
Accounts for prevalence (pretest prob) and for liklihood ratio of test.
= pretest odds x likelhood ratio
Posttest probablility
Postest odds/ (1+postest odds). This makes sense because in betting odds if its 1 in 4 chance, then (simplified) 0.25/1 = 0.25 then 0.25/ 0.25 +1
What is a confusion matrix
For regression. HOw many were and wernt correctly classified based on regression,
Can be used to calculate specificity and sensitivity
Explain why ROC graphs are needed.
For a test you always need a cut off. Increasing threshold decreases true positive but also false positive i.e. less sesnitive but more specific. Decreasing threshold decreases false negative but also true negative - more sensitive but less specific. SO how do you deside threshold? ROC curve`
Axis of ROC
Sensitivity (True pos rate) = y
1- Specificity (False pos rate) = x
What does x=y signify on ROC curve
True postive = false postive
