STRAND B (Ethics) Flashcards
clinical trial
interventional study with IMP’S
clinical study
research with human volunteers/ participants intended to add to medical knowledge, can be observational or interventional.
IMP
investigational medicinal products
types of NIH clinical trials
mechanistic
exploratory/ development
pilot/ feasibility
behavioural
other interventional
basic experimental
2 types of study design
experimental
observational
experimental study
researcher intervention and observation
randomised/ non-randomised
observational study
observational no action
cohort studies, case-control, cross-sectional, ecological
randomised control trials
bias elimination
units randomised to experimental/ comparison group with dummy intervention
non-randomised trials
inc. observational/ interventional/ single arm
cohort studies
defined group studied over time
observational
associations between interventions received and subsequent outcome
(prospective > recruitment prior to intervention/ retrospective> recruitment from past records)
case control studies
observational for possible causes of a disease/ condition
compare similar patients with controls
cross-sectional studies
snapshot of set at 1 time
description of variable not measurement > assesses cause and effect and symptom comparison
positives of cross-sectional studies
simple
cheap
quick
minimal error margin
negatives of cross-sectional studies
bias?
doesn’t determine cause/ effect
ecological studies
relationship between outcome and exposure at a population level with same characteristic
phases of a clinical trial
- pre-clinical research
phase I
phase II
phase III
phase IV
pre-clinical research
model desired bio effect of drug
predict treatment outcome in patients
analyse safety
In vitro/ vivo
computer model drug profile
phase1
test in small group of people (safety/ side effects)
months
phase2
larger group testing (100-300)
emphasis on efficacy
preliminary data
years
phase3
large group testing (1000-3000)
safety/ efficacy/ dosage
FDA approval
NDA submission
phase4
post-marketing monitoring
public availability
why did covid vaccines bypass the 10 year journey
previous, tested vaccine technology platform
phase 1/2 combined with previous dosage knowledge
clinical trials considerations
ethics
consent
controls
randomisation
blinding
sample size
statistics
ethics
moral principles governing a person’s behaviour or conducting of an activity
consent
entering research freely with full information
must: understand premise, info supplied with no coercion, time given for consideration, withdrawal rights at any time
bias
systematic errors encouraging one outcome over others
> treatment effect over-estimation
control group
participants not receiving experimental treatment
how are control groups allocated
clinician’s choice
patient choice
consenting vs refused
hospital/ consultant differences
randomisation
process by which treatments are assigned to participants by chance to avoid bias
stratified/ simple/ block
simple randomisation
based on single sequence of random assignments
:) simple/ easy to implement
:( unequal no. among groups
block randomisation
equal sample sizes, balanced in random combinations
:) sample size balance
:( can predict blocks
:( may not be comparable in terms of covariates
stratified
separate blocks generated for each covariate combo and assigned to appropriate covariate block
simple randomisation within each block
:) simple for small trials/ covariate consideration
:( complicated in large groups/ prior identification of subjects
single-blinded
only researcher knows which intervention is being received
doubleblinded
neither researcher/ participant know
what does blinding affect?
patient management
dosage decision
therapy intensity
discharge decision
trial compliance
expectations
assessment outcome
true endpoint
clinically meaningful endpoint directly measuring patients
surrogate endpoint
specific outcome measurement used in place of another as a predictor
result dissemination
releasing findings to maximise benefit of research without delay
- stakeholder engagement
- format
-context
-utilise opportunities
1947 Nuremberg trials code of 10 principles
- voluntary consent
- research for societal good
- previous knowledge justification
- no unnecessary suffering
- avoided if could be fatal
- mitigated and proportionate risk
- adequate facilities
- qualified conductors
- subject withdrawal
- discharged if injury likely
1964 Helsinki declaration
guidance for dual role doctors as clinician/ researcher
ICH-GCP routed
Human participant examples
embryo
recently deceased
living human
foetuses
stored tissues/ fluids
informed consent stages
- giving info
- discussion/ clarification/ review
- written/ verbal consent
- process consent
informed consent in children
16+ can give consent
child’s assent / guardians informed consent
informed consent in vulnerable adults (temp/ permanent)
mental capacity act 2007
medicine for human use regs 2004
common law
HeLa cells (immortal human cells)
helped polio vaccine/ chemo/ cloning/ IVF/ gene mapping
mimicked living human experimentation
Henrietta Lacks (d. 1951) prior to adeno-carcinoma death
no benefit to fam despite commercial billions
Alder-hey organ retention scandal
pathologist collecting organs from children without permission
human tissue act 2004
storage and use of human tissue regulated from deceased
inducement
provision of incentive to entice a person to carry out an action
Tuskagee syphilis study
US public health service
600 poor black males offered free healthcare/ meals/ burial insurance
400 w syphilis and monitored for 40 years
no treatment despite penicillin cure
GDPR
general data protection regulation
7 GDPR principles
- lawfulness, fairness and transparency
- purpose limitation
- data minimisation
- accuracy
- storage limitation
- integrity and confidentiality
- ‘accountability’ principle
medicines act 1968
- after thalidomide scandal
legal standard on supply/ manufacture on 3 classifications of medicine (prescription/ pharmacy/ general
Northwick park 2006
healthy males> experimental antibody drug TGN1412 for rheumatoid arthritis/ autoimmune conditions
Parexel managed
multi-organ failure
ontology
philosophical study of entities
2 ontologies dominating Western philosophy
mechanistic materialism
dualism
mechanistic materialism
ontology that reality is formed of components acting in machine-like fashion
- no consciousness/ free will
- accepts ‘determinism’
- billiard ball universe
determinism
all events determined by causes lacking free will
dualism
view that reality is composed of 2 fundamentally distinct things with minds / without
panexperientialism
view that mind is a fundamental and ubiquitous feature of reality
> differing levels of agency w levels of material and mental complexity
speciesism
treating members of one species morally more important than other species
example of animal rights philosopher
tom Regan
‘view animals as our resources’
animal acts 1986
demands some forms of protection should be applied to ‘any living vertebrate other than man when gestation/ incubation period has elapsed and capable of independent feeding
alternatives to non-human animal research
micro-dosing
observational studies
randomised controlled trials
use of human tissue
computer testinge
examples of misconduct in research
falsification
fabrication
plagiarism
self-plagiarism
gift authorship
4 principles approach for good biomedical research
respect for autonomy
beneficence
nonmaleficence
justice
ethical review process 3R’s
replacement (of sentient w non-sentient)
reduction (no. animals to minimum w/o compromising precision/ value)
refinement (decreasing incidence/ severity of inhumane procedures, suffering evaluation)
ASPA 1986
animals scientific procedures act 1986
- cost benefit analysis
- larger EU legislation
- regulation
- protected species
what does ASPA control?
PPL
People researching w PIL in designation certified place
PPL
purpose of research via project license
PIL
Personal license
- required to carry out reg. procedures
PPL project license
work programme specification for allowable purpose under license holder control
what must a research proposal have
RRR consistent to objectives
knowledge outweighs harm
sufficient knowledge of applicants
clear objectives/ methods
EL
establishment license
named people involved in animal research
EL holder
NVS (Named vet surgeon)
NACWO (Named animal care/ welfare officer)
NIO (info officer)
NTCO (training/ competency officer)
AWERB
animal welfare ethics review board
- assigned per institute
sub-threshold considerations for animal research
less pain than insertion of a hypodermic needle
ASPA schedule 1
humane killing methods
schedule 2
lab animal supply codes of practice
