L10: Ethics in clinical trials Flashcards
recap: what is GCP?
good clinical practice, the international ethical and scientific quality standard for designing, conducting and reporting clinical trials
what is the Hippocratic oath about?
” to never do harm”
recap: what is the US Food drugs and cosmetic act 1938 about?
as harmful drugs were available OTC, FDA require manufacturers to test drugs for safety and report evidence to FDA before marketing
what is the basis for the Nuremberg Code 1946?
during WW2, german physicians experimented on prisoners. Code ensures that there is scientific basis for research on human subjects, and there is voluntary consent and protection of human participants. must have INFORMED CONSENT
what is ICH GCP?
International conference harmonisation’s guideline for good clinical practice–> helps to overcome inconsistencies in GCP internationally
Declaration of Helsinki was developed by ___?
World Medical Association
what are the 3 MAIN POINTS of Belmont Report?
- Respect for persons aka autonomy: need consent
- Beneficence: do no harm and maximise benefits aka non-maleficence
- Justice: equitable selection and recruitment, fair treatment of subjects
recap: what is IRB?
Institutional review board; independent committee established within the university that conducts scientific and ethical review on research involving human subjects
IRB consists of people part of the research team that helps to review research proposal. T/F?
false. they are NOT part of research team [if not will have bias]. but yes they help to review proposal before research is conducted
state the 3 descriptions that guides how IRB operates.
- Nuremberg Code: require scientific basis of clinical trial + voluntary consent
- Declaration of Helsinki: ethical principles to guide physicians in medical research involving human subjects
3.Belmont Report: autonomy/respect, justice, beneficence
it is not compulsory for drugs to be tested on animals before doing clinical trials on humans. T/F?
False. must be tested on animals first to check for safety before trying on humans. use as few animals as possible
describe the diff phases of clinical trials [4]
phase 1: first in man. determine DOSING, how drug is metabolised, identify ADVERSE EVENTS
phase 2: safety + efficacy
phase 3: efficacy-> try on greater number of participants and monitor side adverse effects
phase 4: for approved products. find out about long term risks
what is a protocol for clinical trial?
a document that describes the objectives, design, methodology, statistical considerations and organisation of trial
For clinical trial protocol, the general info segment should include: [4]
- title, identifying number, date, amendment number&date
- sponsor’s details: name, address, signee and medical expert details
- investigator details: name title address phone number
- contact deets of doctor responsible for all trial site related medical decisions
For clinical trial protocol, the background info segment should include: [6]
- name and description of IP
- summary of relevant non-clinical and clinical studies
- summary of known/potential risks and benefits
- Treatment details: description, justification of administration route, dosage and duration
- statement that trial will be conducted in compliance with protocol, GCP and regulatory requirements
6, description of study population
For clinical trial protocol, the trial design segment should include: [6]
- primary/secondary endpoints
- type/design
- diagram of procedures and stages
- measures to reduce bias: eg. randomisation and blinding
- trial treatment, dosage, regimen
- dosage form, packaging, labelling
to assess efficacy of drugs in clinical trials, we need to measure __
efficacy parameters: methods and timings for assessment, recording and analysis of efficacy parameters
In the case study regarding Schizophrenia and Tony LaMadrid, what was the problem? [to observe behaviour of patients when taken off medication]
There was no control environment and participants were not taken care of and properly monitored. Did not prioritise beneficence of patient. Who decides that patient is not well?
In the case study of Nicole Wan and airborne chemicals, what was the problem?
Lidocaine was inhaled at high dose, which was never done before
in the case study about Jesse Gelsinger and gene therapy, what was the problem?
informed consent signed by Jesse did not include the word ‘death’, unlike that reviewed by IRB
in the case study of elephant man trial, where 1 dose of drug containing monoclonal antibody was injected in human subjects, what was the problem?
preclinical studies failed to consider what constituted to a safe dose for use in humans
In the case study of Ellen Roche and asthma/hexamethonium inhalation, what was the problem?
Drug name was not mentioned explicitly in the consent. most people will not join study if they know the drug and its side effects
what is the method to justify intervention has therapeutic efficacy?
randomised controlled trial
features and challenges of RCTs [3]
- randomisation: participants are ASSIGNED into experimental or control groups
- control group given placebo or a standard intervention [if study is studying NEW intervention]
- blinding/masking: reduce potential bias. single or single blind
