L10: Ethics in clinical trials

Question 1

recap: what is GCP?

Answer 1

good clinical practice, the international ethical and scientific quality standard for designing, conducting and reporting clinical trials

Question 2

what is the Hippocratic oath about?

Answer 2

” to never do harm”

Question 3

recap: what is the US Food drugs and cosmetic act 1938 about?

Answer 3

as harmful drugs were available OTC, FDA require manufacturers to test drugs for safety and report evidence to FDA before marketing

Question 4

what is the basis for the Nuremberg Code 1946?

Answer 4

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

Question 5

what is ICH GCP?

Answer 5

International conference harmonisation’s guideline for good clinical practice–> helps to overcome inconsistencies in GCP internationally

Question 6

Declaration of Helsinki was developed by ___?

Answer 6

World Medical Association

Question 7

what are the 3 MAIN POINTS of Belmont Report?

Answer 7

1. Respect for persons aka autonomy: need consent
2. Beneficence: do no harm and maximise benefits aka non-maleficence
3. Justice: equitable selection and recruitment, fair treatment of subjects

Question 8

recap: what is IRB?

Answer 8

Institutional review board; independent committee established within the university that conducts scientific and ethical review on research involving human subjects

Question 9

IRB consists of people part of the research team that helps to review research proposal. T/F?

Answer 9

false. they are NOT part of research team [if not will have bias]. but yes they help to review proposal before research is conducted

Question 10

state the 3 descriptions that guides how IRB operates.

Answer 10

1. Nuremberg Code: require scientific basis of clinical trial + voluntary consent
2. Declaration of Helsinki: ethical principles to guide physicians in medical research involving human subjects
   3.Belmont Report: autonomy/respect, justice, beneficence

Question 11

it is not compulsory for drugs to be tested on animals before doing clinical trials on humans. T/F?

Answer 11

False. must be tested on animals first to check for safety before trying on humans. use as few animals as possible

Question 12

describe the diff phases of clinical trials [4]

Answer 12

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

Question 13

what is a protocol for clinical trial?

Answer 13

a document that describes the objectives, design, methodology, statistical considerations and organisation of trial

Question 14

For clinical trial protocol, the general info segment should include: [4]

Answer 14

1. title, identifying number, date, amendment number&date
2. sponsor’s details: name, address, signee and medical expert details
3. investigator details: name title address phone number
4. contact deets of doctor responsible for all trial site related medical decisions

Question 15

For clinical trial protocol, the background info segment should include: [6]

Answer 15

1. name and description of IP
2. summary of relevant non-clinical and clinical studies
3. summary of known/potential risks and benefits
4. Treatment details: description, justification of administration route, dosage and duration
5. statement that trial will be conducted in compliance with protocol, GCP and regulatory requirements
   6, description of study population

Question 16

For clinical trial protocol, the trial design segment should include: [6]

Answer 16

1. primary/secondary endpoints
2. type/design
3. diagram of procedures and stages
4. measures to reduce bias: eg. randomisation and blinding
5. trial treatment, dosage, regimen
6. dosage form, packaging, labelling

Question 17

to assess efficacy of drugs in clinical trials, we need to measure __

Answer 17

efficacy parameters: methods and timings for assessment, recording and analysis of efficacy parameters

Question 18

In the case study regarding Schizophrenia and Tony LaMadrid, what was the problem? [to observe behaviour of patients when taken off medication]

Answer 18

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?

Question 19

In the case study of Nicole Wan and airborne chemicals, what was the problem?

Answer 19

Lidocaine was inhaled at high dose, which was never done before

Question 20

in the case study about Jesse Gelsinger and gene therapy, what was the problem?

Answer 20

informed consent signed by Jesse did not include the word ‘death’, unlike that reviewed by IRB

Question 21

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?

Answer 21

preclinical studies failed to consider what constituted to a safe dose for use in humans

Question 22

In the case study of Ellen Roche and asthma/hexamethonium inhalation, what was the problem?

Answer 22

Drug name was not mentioned explicitly in the consent. most people will not join study if they know the drug and its side effects

Question 23

what is the method to justify intervention has therapeutic efficacy?

Answer 23

randomised controlled trial

Question 24

features and challenges of RCTs [3]

Answer 24

1. randomisation: participants are ASSIGNED into experimental or control groups
2. control group given placebo or a standard intervention [if study is studying NEW intervention]
3. blinding/masking: reduce potential bias. single or single blind

Question 25

how can we strengthen international ethical agreements on clinical trials?

Answer 25

• govt regulatory office need to review all records of trials
• doctors need to provide videos of their conversations with each subject during consent signing
• companies need to conduct investigation of suspicious cases
• external companies to audit

Question 26

what was the issue with Sanofi’s epilepsy medication?

Answer 26

side effects were not fully disclosed. medication were found to birth defects

Question 27

what was the issue with trials related to covid treatment?

Answer 27

• non-randomised
• not blinded

Question 28

what was the issue with trial on covid treatment regarding Remdisivir?

Answer 28

• patients were not well selected, characterisation of covid patients not carried out correctly
• 30% from Iran, which had high mortality rate due to late start of treatment and non-compliance –> BIASED RESULTS

Question 29

what are some ethical considerations of current covid vaccine intervention and development?

Answer 29

• vaccine is for HEALTHY human subjects who have not gotten covid, hence risk-benefit would be diff
• some vaccine uses mRNA technology, which has not been used before in a widely distributed vaccine
• vaccine candidates must fulfil several requirements: safety, efficacy and quality