S4-1_Nurain Mohd Noor
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DR NURAIN MOHD NOOR
CHAIRPERSON ,MEDICAL RESEARCH &
ETHICS COMMITTEE, MINISTRY OF
HEALTH, MALAYSIA
CASE STUDIES IN
ETHICAL CHALLENGES
DURING COVID-
19: VACCINE CHALLENGE
TRIALS
• Background
• Covid-19 vaccines Studies Statistics
• Case Study I
• Case Study II
OUTLINES
FIRST CASE OF COVID IN MALAYSIA – 25/1/2020
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MOVEMENT CONTROL ORDER
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FIRST VACCINATION ON THE 24 FEBRUARY 2021
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MY SEJAHTERA APP
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• With the MCO, Medical Research & Ethics Committee (MREC),
Ministry of Health Malaysia -the method of meeting to virtual
meeting to ensure the continuity of its functions.
• Ad-hoc meeting with quorum held virtually
BACKGROUND
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• 12 applications for COVID-19 vaccines
– 6 approved via full board review
– 6 have incomplete submission
COVID-19 VACCINES STATISTICS
• Overview of the Trial
• Efficacy study: A randomized, double-blinded and placebo-
controlled design involving 32,820 healthy subjects aged 18
years and above
• 1:1 ratio – randomly inoculated with two doses of
investigational vaccine or placebo following Day 0-Day 14
immunization schedule
• collect symptomatic and laboratory-confirmed COVID-19
cases
CASE STUDY 1: SARS-COV-2 VACCINE, INACTIVATED
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• Nov 2020
• Ethical review
– The expertise and experience of the study team
– The study site has the appropriate facilities – cold chain of the vaccine is
maintained and facilities required to conduct vaccine trial.
• Approved in Dec 2020
ETHICAL REVIEW AND DECISION ONTHETRIAL
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• National Vaccination Programme for COVID-19 virus on
24 Feb 2021 (2 months after the study is approved)
• Restricted social activities are allowed for those
completed 2 doses of vaccination on 8 Aug 2021
WHAT HAPPENED AFTER THAT?
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• high withdrawal as participants no longer willing to stay
in the study as they had limitation in social activities.
• high protocol deviations in which study participants had
deviated from protocol and obtained other vaccines from
National Vaccination Programme.
THIS LED TO ….
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• Study participants were unblinded and updated their
vaccination status to allow them to involve in the social
activities.
• Placebo arm was given vaccines
• Study design was amended to cross over.
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• Introduction of booster shot in February 2022 to maintain
the “fully vaccinated” status and enjoy the privilege of
mobility.
• The inactivated vaccine platform seems to show lower
protection level even with a booster dose.
• The study vaccine may not be able to confer sufficient
protection efficacy against Omicron VOC infection
HOWEVER THE STUDY WAS TERMINATED
• a multi-national, endpoint-driven, randomized, double-
blind, placebo-controlled, adaptive study in which
participating adults will be randomized 1:1 to receive 2
doses of either candidate vaccine or placebo on Day 0 and
28.
CASE STUDY 2: PHASE III STUDY OF SARS-COV-2 VACCINE
INACTIVATED FROM INSTITUTE OF MEDICAL BIOLOGY
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• National immunization program of COVID-19 leading to subjects
in this study excluded from the vaccination program
• Clearly state regarding the risk of exclusion from national
vaccination program in the Patient Informed Consent
• Following satisfactory feedback from the PI on 15 Apr 2021,
study was approved on 23 Apr 2021.
ETHICAL REVIEW
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• Low recruitment rate
• Report that the study was done at the sites not approved by
MREC
• Had an audit compliance review to the study sites
– One of the study sites had extended the vaccination outside
the facility
– Informed consent documentation insufficiency
– Use of unapproved patient facing materials by the study
teams.
CASE STUDY 2
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• Corrective actions and preventive actions had been done
accordingly.
• However, this study was terminated due to unable to enroll
sufficient study participants following the change of
national policy for COVID-19.
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• Maybe there is a better drug with
less side effects?
• Depriving the patient of getting
effective treatment ?
• Uses of placebo if
– There is no proven effective
intervention
– Not to treat poses negligible
risks of participation
– Compelling methodological
reasons for using placebo and
not to treat does not imply in
risk of serious harm to
participant
PLACEBO CONTROLLED ?
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• Timely Risk Communication to trial participants are crucial to ensure
right, safety and well-being of trial participants.
• State clearly in the informed consent
• Patient understood the risks in the study
LESSONS LEARNT
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• COVID-19 virus pandemic are dynamic, clinical trial protocol must be
able to adapt to the national response system as well.
• Variants of COVID-19- whether the study is still relevant to be continued
or modifications are required to ensure its scientific validity.
• Communications to study participants – clear and updated from time to
time to ensure retention without need to compromise their daily
activities due to their involvement in COVID-19 vaccines trial.
LESSONS LEARNT
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• Study team must be aware and ready to terminate a study when
recruitment is below their expectation.
• Compliance review is important to ensure safety and well being of trial
participants.
LESSONS LEARNT
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• Covid 19 pandemic gave opportunity of different design and
methodology in conducting clinical trials
• Each study is different and managing the challenges should be
individualized
• Importantly the safety and wellbeing of the patient is the utmost
priority
CONCLUSION
THANKYOU!
DR NURAIN MOHD NOOR
EMAIL:PPNURAIN@HPJ.GOV.MY