Elements of a clinical trial
research protocol
Outline
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Identify the session objective
Discuss the content of a clinical trial protocol
Discuss the content of observational study
Conclusion
Study objective
• Participants will learn about the essential elements
of a clinical trial protocol
• Participants will learn about the essential elements
of a protocol developed for observational studies
• Participants will learn about existing reporting
guidelines that should inform the design and
reporting of study protocols
Elements of a clinical trial protocol
• TITLE: Identification as a randomised trial in the title
• INTRODUCTION: Scientific background and
explanation of rationale
• SPECIFIC OBJECTIVES OR HYPOTHESES: the
objectives could be primary, secondary and or
tertiary (exploratory)
Content of a protocol for clinical
trials- 2
METHODOLOGY:
• Trial design: description of trial design (such as
parallel, factorial) including allocation ratio
• Study participants: Eligibility criteria; Settings and
locations where the data were collected
• Intervention: interventions for each group with
sufficient details to allow replication, including how
and when they will be administered
Content of a protocol for clinical
trials- 3
METHODOLOGY:
• Sample size: Sample size determination; explanation
of any interim analyses and stopping rules if
applicable
• Randomisation sequence generation: Method used
to generate the random allocation sequence; Type of
randomisation; details of any restriction (such as
blocking and block size)
Content of a protocol for clinical
trials- 4
METHODOLOGY:
• Allocation concealment mechanism: Describe any
step or mechanism to be taken to conceal the
sequence until interventions were assigned such as
sequentially numbered containers.
• Implementation plan: Who generated the random
allocation sequence, who enrolled participants, and
who assigned participants to interventions.
Content of a protocol for clinical
trials- 5
METHODOLOGY:
• Blinding: Describe those to be blinded after assignment
to interventions (for example, participants, care
providers, those assessing outcomes) and how
• Statistical method: Statistical methods to be used to
compare groups for primary and secondary outcomes;
Methods for additional analyses, such as subgroup
analyses and adjusted analyses
Content of a protocol for
observational studies
• TITLE: Indicate the study’s design with a commonly
used term in the title
• BACKGROUND/INTRODUCTION: Explain the
scientific background and rationale for the
investigation being reported
• OBJECTIVE/HYPOTHESIS: State specific objectives
Content of a protocol for
observational studies - 2
METHODOLOGY
• Study design: Present key elements of study design
• Setting: Describe the setting, locations, periods of
recruitment, exposure, follow-up, and data collection
plans
Content of a protocol for
observational studies - 3
METHODOLOGY
Study participants:
• Cohort study: Give the eligibility criteria, and the sources
and methods of selection of participants. Describe methods
of follow-up
• Case-control study: Give the eligibility criteria, and the
sources and methods of case ascertainment and control
selection. Give the rationale for the choice of cases and
controls
• Cross-sectional study: Give the eligibility criteria, and the
sources and methods of selection of participants
Content of a protocol for
observational studies - 4
METHODOLOGY
Study participants for matched studies:
• Cohort study: give details on matching criteria and
number of exposed and unexposed
• Case-control study: give details on the matching
criteria and the number of controls per case
Content of a protocol for
observational studies - 5
METHODOLOGY
• Variables: Clearly define all outcomes, exposures,
predictors, potential confounders, and effect modifiers.
Give diagnostic criteria, if applicable
• Data sources and measurement: For each variable of
interest, give sources of data and details of methods of
assessment (measurement). Describe comparability of
assessment methods if there is more than one group.
Content of a protocol for
observational studies - 6
METHODOLOGY
• Bias: Describe any efforts to address potential
sources of bias
• Study size: Explain how the study size was arrived at
• Quantitative variables: Explain how quantitative
variables will be handled in the analyses. If
applicable, describe which groupings will be chosen
and why.
Content of a protocol for
observational studies - 7
METHODOLOGY
• Statistical methods: Describe all statistical methods,
including those to be used to control for
confounding; Describe any methods used to examine
subgroups and interactions; Explain how missing
data will be addressed.
Content of a protocol for
observational studies - 8
METHODOLOGY
Statistical methods:
• Cohort study: If applicable, explain how the potential
for loss to follow-up will be addressed
• Case-control study: If applicable, explain how
matching of cases and controls will be addressed
• Cross-sectional study: If applicable, describe
analytical methods taking account of sampling
strategy
Clinical trial and cohort studies
Differences between clinical trial and cohort studies
• Clinical trials generates a prove of concept
• Cohorts studies generate evidence to support or
disprove a concept
Processing protocols
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Health Research Ethics Committees
National Health Research ethics committees
NAFDAC
Data Safety and Monitoring Boards
Handling of the research protocol
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Exempt
Expedited approval
Full committee review
Renewal of ethical clearance
Handling of protocol amendments
Reporting on adverse events
Regulatory Definitions
Adverse Event (AE) or Adverse Experience
Any untoward medical occurrence in a patient to
whom a medicinal product has been
administered, including occurrences which are
not necessarily caused by or related to that
product.
An adverse event does not necessarily have a
causal relationship with the medicinal product.
Regulatory Definitions
Serious Adverse Event (SAE):
An adverse event that meets one of the following
criteria's is considered serious:
1. Death
2. Life threatening
3. Involves initial hospitalisation or prolongs
hospitalisation
4. Results in permanent or significant disability
5. Results in a congenital anomaly or birth defect
6. Considered medically important by the
Investigator
Timelines for Adverse Event
Reporting
• All SAE’s must be reported to the sponsor or
appropriate handler within one business day of an
individual i.e. Investigator becoming aware of the
event.
• Deaths and Life -Threatening events should be
reported to sponsor immediately by telephone and
should be followed up within one business day with a
completed SAE form.
Reporting guidelines
• CONSORT Statement on reporting of randomized
controlled trials
• STARD on reporting of diagnostic accuracy studies
• STROBE on reporting of observational studies in
epidemiology
• PRISMA on reporting of systematic reviews
• MOOSE on reporting of meta-analyses of
observational studies
Conclusion
• There are global standards to design and reporting of
research
• The standardisation enables uniformity of research
activities across the globe.
• The process ensures data generate are comparable
across regions and sites
Thank You
and
Questions
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Elements of a clinical trial research protocol by Dr Morenike