The Study Protocol: part two

Contents
1. Contents
2. Course Objectives and Content
3. Course layout
4. Data Collection and Management
1. Data Collection and Management
5. Monitoring Study Safety, Quality and Data
1. Monitoring Study Safety, Quality and Data
6. Adverse Event Reporting
1. Adverse Event Reporting
7. Analysis Strategies and Statistical Considerations
8. Setting up a Research Team
9. Post-Recruitment Retention Strategies
10. Economic Evaluation
11. Clinical Laboratories
12. Results Reporting, Dissemination and Notification
13. References and Appendices
14. Protocol Amendments and Modifications
1. Protocol Amendments and Modifications
15. Common Problems
16. Considerations When Protocol Writing
17. Key Points to Remember
18. References and Resources
19. Quiz

Course Objectives and Content

Objectives

Upon completion of this course, you will have an understanding of:

what a protocol is and why it is necessary

the basic concepts of designing a protocol
the sections that should be included in a protocol
points to remember when creating a protocol
common errors that should be avoided when developing a protocol

Contents

- This course will look at the following:

What a protocol is
The topics that are covered by a protocol
Common problems encountered when writing a protocol
Making amendments to a protocol

- Key Points to Remember

- References and Resources

This section provides the references used in this course and resources that you may find useful
for further reading.
- Quiz

This section provides questions that will allow you to test what you have learned from the
course.

Course layout
This e-course is divided into parts one and two.

Part one will cover the following:

1. General Information
2. Background and rationale
3. Aims and objectives
4. An overview of the research question and the study design
5. Methodology, interventions and allocations
6. Outcome measures
7. The sample size
8. Study population
9. Ethical aspects
10. Participant and community engagement
11. Research governance
12. Study management
13. Key points to remember
14. References and resources
15. Quiz

Part two will cover the following:

1. Data collection and management

2. Monitoring study safety, quality and data
3. Adverse event reporting
4. Analysis strategies and statistical considerations
5. Setting up a research team
6. Post-recruitment retention strategies
7. Economic evaluation
8. Clinical laboratories
9. Results Reporting, Dissemination and Notification
10. References and appendices
11. Protocol amendments and modifications
12. Common problems
13. Considerations when writing a protocol
14. Key points to remember
15. References and resources
16. Acknowledgements
17. Quiz

Data Collection and Management

‘In parallel with the development of the protocol, the data to be collected to answer the study
objectives should be defined’ (McFadden, 2007). Prior to the start of the study the data
management systems should be decided upon and these should be described in the protocol.
As with a statistical plan, it is also good practice to write a separate data management plan
which can be referred to and summarised in the protocol.

As recording the study data is considered to be the most crucial stage of the data management
process, high data quality is essential. To improve the reliability and validity of the source data,
it is important to get the processes and procedures for data collection correct from the start, as
later on there is little you can do to improve the data quality. Defining the source data is
important, although this might be captured in detail in the data management plan rather that
the protocol.

A data capture form (DCF) turns the protocol into the data capture system. The 2002 ICH GCP
guidelines define a DCF as a printed, optical, or electronic document that ‘is designed to record
all of the protocol required information to be reported to the sponsor on each trial subject’. A
DCF can also be used to document where the source information can be found e.g. medical
notes, scans and X rays. The term 'case record form' or CRF is also commonly used for the data
capture tool.

Data Collection and Management

All studies on human participants should have an assured level of quality to protect the rights of
the participants and to ensure that data are reliable. As the quality of the data is entirely
dependent on well-designed DCFs, it is crucial that adequate time is invested in creating these
forms. The DCFs should only collect data listed in the protocol and nothing else.

As McFadden (2007) points out ‘if using paper data capture forms, there is a need for systems
for (a) distributing blank paper forms to the participating sties and (b) for returning completed
forms in a timely way to the Coordinating Centre. If data is captured electronically, hardware
and software must be developed and fully tested and validated. If samples are being collected
as part of the study (e.g. X rays, blood/tissue samples), mechanisms should be in place for
shipping, receipt, and logging of sample’.

Some of the issues that you may want to consider when deciding upon your data management
systems include:

Data collection: when possible piloting testing of the methods

and of the DCFs to be used will help highlight any problems and
allow you to resolve them before the study begins
Data entry: will this be done during the study or once it is
finished, will it be single or double data entry
Database: if using electronic systems what type of system should
be used (e.g. Open Clinica for trials, OpenXdata for
epidemiological studies), how will it be secured and what sort of
audit trail system should be used
Data processing: will it be managed manually or by computer
Data coding: will it be carried out during data collection or
afterwards and by whom
Data validation: how will both validation for completeness and
accuracy and the data cleaning be undertaken and when will these tasks be done
Data analysis: what tests will be used and when will they be carried out
Data storage: how will the data be stored and for how long

It is important to remember that no matter how well a study is run, if the study does not capture
the correct data, meaningful analysis may not be possible. It is therefore important to have
quality control systems in place for data checking, audit trails and source verifications
procedures.

Monitoring Study Safety, Quality and Data

The procedures for data, quality and safety monitoring should be
described and should reflect the risk and complexity of the trial.
The Principal Investigator is responsible for the monitoring of
participant safety, study data and quality assurance. The WHO's
Research Ethics website stresses that ‘the safety of research
participants is foremost. Safety aspects of the research should
 always be kept in mind and information provided in the protocol on
how the safety of research participants will be ensured. It is useful
to remember that even administering a research questionnaire can
have adverse effects on individuals’.

This section is often split into quality management and safety monitoring.

In terms of safety of the participants the Principal Investigator is responsible for monitoring,
assessing, recording and reporting on all adverse events related to the study to the sponsor and
data safety monitoring board (DSMB). Procedures for continually reviewing the risk-benefit
status should also be provided.

Interventional studies may wish to evaluate efficacy or safety issues around the intervention(s)
during the study’s progress. This evaluation is called an interim analysis. If interim analyses are
planned the timings and processes should be explained. If applicable, formal statistical stopping
guidelines can be applied to the interim analyses in case any evidence of unacceptable risk or
actual harm is uncovered by the analyses. Any stopping rules should be laid out and justified.

Monitoring Study Safety, Quality and Data

Quality control is important in clinical trial as this assures that the study has been conducted
ethically and that the data is reliable. In the protocol there should be clear
description of how quality will be achieved and maintained.

The study set up must have clear, comprehensive internal and external
quality systems which ensure that the quality of the procedures, and the
results generated, are reliable and valid. The description of the data
handling procedures should include plans for data checking (how much will
be checked, by whom, and how); audit trails (detailed log showing which
data have been changed, why it was changed, who changed it and when);
and source verification procedures (how much data will be checked
against the source documents e.g. medical records).

The difficulties anticipated throughout the duration of the study should be listed. The potential
solutions to these anticipated problems should also be outlined.

All clinical research should have an appropriate level of safety monitoring and quality
management to protect the rights of the individual and to ensure that the data and procedural
qualities are reliable. It is important to also remember the resource and cost implications when
committing to levels of monitoring and quality assurance in the protocol. They should be
proportionate to the risks of the study.

Adverse Event Reporting

An adverse event is defined as any type of medical event (e.g. a symptom, side effect or
laboratory finding) which is temporally linked to the investigational intervention and may (or
may not) be caused by it. The protocol should specify which grades of events will be recorded,
as many studies do not require the recording of minor events.

A serious adverse event (SAE) is any unexpected outcome in a participant

which results in death, is life-threatening, requires hospitalisation (or
prolongs existing hospitalisation), results in persistent/significant disability or
results in a birth defect (congenital abnormality). It may or may not be
related to the intervention (Global Health Trials Glossary: see the Resources
section of this course).

Mulay (2001) stresses that 'reporting SAEs is your highest priority after participant care'.

The WHO’s 2005 Draft Guidelines for Adverse Event Reporting and Learning Systems advises
that non-serious events are recorded in the study's data collection forms alongside the other
data. SAEs are usually collected on a specially designed form. If the study plans to use these
forms, the data they will collect should be outlined, described, and justified. Actual and potential
risks of participating must also be described in detail. Efforts to minimize these risks must be
clearly explained.

Adverse Event Reporting

Fedor et al. (2006) state that the sponsor usually requires the following information when
reporting an adverse event:

Route, dose, date and time of administration of the investigational

product
Date of report to sponsor
Nature of adverse event
Date and time of onset of adverse event
Duration of event
Resolution (if applicable)
Laboratory data
Concomitant medications
Investigator’s assessment of severity classification
Investigator’s assessment of the relationship of the investigational product
The details of the person reporting the adverse event
Actions that were taken
Follow-up information

SAEs should usually be reported to the coordinator (or principle investigator if there is no
coordinator) within 24 hours. The coordinator or principle investigator should inform the Data
Safety Monitoring Board (DSMB), Ethics Committee and sponsor, typically within a week.
Generally studies will only report serious, unexpected and possibly related events, to the DSMB,
ethics committee and sponsor.

It may be that a DSMB is required to independently review adverse events. These are by no
means always needed and often a local independent safety monitor is a very acceptable step
for monitoring safety. Trials evaluating investigational new products often have a local safety
monitor and a DSMB. Whether a DSMB is needed is dependent on the type of intervention, the
sponsor's requirements and local regulations.

Analysis Strategies and Statistical Considerations

The protocol needs to explain the statistical objectives of your study and how the number of
participants was determined. Later a separate and full statistical analysis plan
sets out how you will analyse the data. This should however be summarised in
the protocol.

Details of the proposed analysis of the primary and the secondary objective(s)
should also be included. If it is not possible to have a statistician write the
statistical analysis plan, it should at least be commented on by one.

The statistical analysis plan outline can be altered during the course of the study, for example
after requests for interim analyses, but it should be finalised before the database is ready for
the full data analysis as this avoids the risk of the data being manipulated. A statistical analysis
plan has the advantage of preventing unplanned analyses at the end of the study but it should
not stop further examination if unusual features of the data are identified during the analyses.

Setting up a Research Team

A study requires a team of professionals to help design and implement the various stages
involved. The type of study you are planning will determine both the personnel and the sort of
training required to safely and efficiently carry out the study procedures. A complex trial might
need a team made up of individuals from many different roles who have a shared interest in the
topic and can bring to the table an area of expertise.

Toto and McPhaul (2011) state ‘the investigator must invest in building a research team that
consists of individuals (e.g., study coordinator, co-investigators, biostatistician, research and
laboratory technicians, and administrative support) that have the level of expertise required to
navigate through the various study challenges'. Of course this depends upon the size and
complexity of your study. The requirements of a year long complex multi-centre trial of an
experimental new malaria vaccine will be vastly different from a small phase II 'proof of
concept' trial with 40 participants evaluating whether to treat pneumonia at home or on the
ward.

Having the right staff is essential to the success of your study. The following should be taken
into consideration when deciding on the make-up of your research team:

How many staff you will need

What disciplines and backgrounds would be most beneficial
to have on the team
The skills and experience that will be needed to undertake
the different tasks and activities that have to be carried out
The responsibility of each member of staff and the training
each will require
The length of contract you will need for each member of the team

Once you have funding secured and have an outline of the research team you will need, you can
begin to hire staff members in order of requirement e.g. laboratory staff won’t be needed until
you have samples to work on but the study co-ordinator will need to be in place as soon as
possible to begin tasks like developing the protocol, seeking regulatory approvals and
establishing the various groups.

Post-Recruitment Retention Strategies

Long term studies or those that will require follow-up should consider how they are going to
retain their participants over the lifetime of the study. Strategies for
encouraging individuals to continue to attend appointments, complete
questionnaires, provide samples etc. will need to be planned, provided for and
described in the protocol. Strategies will also have to be considered for
keeping investigators and study sites interested and actively participating in
the research.

Continued data collection is only possible with the on-going interest and interaction of both the
study’s recruits and the study centres, this therefore must be planned for before the study
begins.

Options such as planning collaborator meetings, producing newsletters and posters, and sending
out merchandise should be listed if you intend on using them during the course of the study.

Economic Evaluation
An economic evaluation is the comparison of the costs and consequences of the
alternative courses of action with regards to issues such as a treatment, a health
care provision and drug options. Some studies may want to consider including a
health economic evaluation in their protocol. These can be highly beneficial if a
trial is evaluating a new intervention in a resource-limited environment.

Hackshaw (2009) lists three features of an economic evaluation in a study:

 a comparison between two or more interventions, even if the comparison group received
no intervention
treatment effect on a clinical endpoints(s)
costs, particularly financial costs, associated with the interventions

The point is to decide whether or not one intervention is more cost effective than another by
weighing up both efficacy and costs. The most inexpensive treatment is not always the
recommended one. Hackshaw (2009) suggests that the ‘treatment of choice is likely to be both
cheaper and more clinically effective’.

Clinical Laboratories
Many clinical studies involve the collection and analysis of samples. The
protocol therefore needs to state how these will be collected and by whom.
Sample collection time can be critical, either for diagnostics or often for
pharmacokinetics. It is often helpful to ensure sample collection is included in
the study flow diagram.

Sample labelling, tracking and management is very important; often the

laboratory samples measure a critical endpoint in the study and so careful thought is needed on
managing, handling and analysing the samples so that errors can be avoided.

A laboratory management plan is typically written as a separate document but key points should
be written in the protocol.

Results Reporting, Dissemination and Notification

A publication policy for all reports and scientific papers that result from the study should be
documented in the protocol.

Authorship should also be discussed in the protocol. Large collaborative studies have group
authorship with a list of contributors at the end of the paper e.g. the participants, the Steering
committee, the DSMB and the collaborating researchers.

As the WHO's Research Ethics website points out that ‘the protocol
should specify not only dissemination of results in the scientific media,
but also to the community and/ or the participants, and consider
dissemination to the policy makers where relevant. Publication policy
should be clearly discussed - for example who will take the lead in
publication and who will be acknowledged in publications, etc’.

Disseminating results to the public is essential. If you do not disseminate the results, the time,
resources, and commitment which have been invested into the study will have been in vain as
no one will get to learn from your research.

Some funders may require that any resulting publications are Open Access. You should be
aware of your funders policy with regard to this and outline an appropriate plan in the protocol if
this is something they require.

References and Appendices

A bibliographical reference might cite all of the resources e.g. papers,
articles, websites, you used in your protocol. You should provide all of
the necessary information to allow someone else to access the same
resources. When citing your references you should be consistent and
accurate using the same set of rules for every reference you list. There
are free tools (e.g. Zotero) which are very useful for tracking references
and inserting bibliography in documents.
The protocol appendices should contain the following where applicable:

A sample of each of the study DCFs that will be used can be included
Budget details
Study timeline
Dummy tables
Statistical analysis plan

Protocol Amendments and Modifications

If, during the course of the study it is found that, for example, extra procedures are required,
different tests need to be used, or changes made to the inclusion or
exclusion criteria then approval must be sought from the same
committees that approved the first version. Generally a written
request for a protocol amendment should be submitted and written
approval obtained for the change, before the changes are
implemented (unless it is being made on the grounds of safety).
However this can change according to local regulations.

A record of the amendments with version numbers and dates on all relevant documents must
be kept. For example, if it becomes obvious that altering the method of statistical analysis
would be beneficial, or that adding an extra statistical test would produce a more credible result,
the section describing this in the protocol will need to be amended. Once approval has been
sought and granted, the protocol should be amended. The updated protocol should be marked
‘Version 2’ and should be dated. If a further change is ever made to the document it will then
become version 3, with the appropriate date included.

Protocol Amendments and Modifications

It is important to understand the difference between a protocol amendment and protocol
modification. Modifications are administrative changes such as change in investigators and are
not considered to be an amendment, but the same committees need to be notified in writing of
any modifications. Modifications are changes that do not impact the participants, the design or
study endpoints. In comparison, a protocol amendment is a change that impacts the
participants, the endpoints or the design.

A well written protocol, developed through careful consultation, will help reduce the need for
amendments. However, sometimes amendments are important and fully warranted to improve
a study. For example, sample size calculations are often set using assumptions and until the
study is underway these cannot be fully predictive. In practice, the nature of a disease or the
numbers presenting may be different and so a change in the number of participants is needed.

Common Problems
There are a series of problems that commonly occur with protocols which lead to the weakening
or failure of a study. When preparing your protocol you should be aware of the
following:

The protocol being too ambitious e.g. trying to answer too many questions, it is best
to have one clear primary objective.
Lack of background knowledge and previous research in your topic of interest,
combined with lack of discussion with all collaborators, partners, the community and
the research team.
An inadequate description of the proposed study and a clear description of the aim.
Poor justification for the study. You must be able to clearly justify the need for the
research, show why is it important to answer this question and explain the impact it will
 have on public health.
Inappropriate statistical analysis e.g. using tests that will not produce the required results
Lack of piloting or testing any of the study methods and instruments.

Considerations When Protocol Writing

When writing a protocol for a proposed study you should consider the following points:

1. Planning is essential, many months may be required to prepare and finalise a protocol.
2. It is important to be aware of the funding policy and procedures of your funder and to
ensure your budget is as realistic as possible.
3. Background knowledge in the proposed area of research is key so it is important to know
what research has already been carried out on the study topic.
4. It is advisable to have the tasks and responsibilities off all partners clearly outlined to avoid
confusion later on.
5. The protocol is not finalised until all peer-review suggestions are obtained, and where
applicable, incorporated.

Not every study protocol will need to cover all of the topics covered in parts one and two of this
course. The study design will dictate which will be relevant and which will not e.g. a complex
clinical trial of a new investigational drug should have all of the sections discussed within this
course included in the protocol but a small cross sectional survey will not need to include
sections on, for example, ‘Economic Evaluation’ or ‘Interventions and allocations’.

Key Points to Remember

It is important to get the processes and procedures for data collection correct from the
start, as later on there is little you can do to improve the data quality.
The principal investigator is responsible for monitoring participant safety, study
data, quality assurance and adverse events.
SAEs should usually be reported to the coordinator or principle investigator within
24 hours. They should inform the DSMB, Ethics Committee and sponsor, typically
within a week.
The protocol should include a summary of the study’s statistical analysis plan.
A study requires a team of professionals to help design and implement the
various stages involved.
Long term studies or those with follow-up should include any planned retention
strategies in the protocol.
An economic evaluation is the comparison of the costs and consequences of the
alternative courses of action with regards to a treatment, a health care
provision, drug options, etc., and is something a large interventional study may
wish to include in their protocol
Many clinical studies involve the collection and analysis of samples. The protocol therefore
needs to state how these will be collected, by whom, how they will be handled, managed
and analysed.
Disseminating results to the public is essential. A publication policy for all reports and
scientific papers that result from the study should be documented in the protocol.
A bibliographical reference might cite all of the resources e.g. papers, articles, websites,
you used in your protocol. You should provide all of the necessary information to allow
someone else to access the same resources.
Generally a written request for a protocol amendment should be submitted and written
approval obtained for the change, before the changes are implemented (unless it is being
made on the grounds of safety). However this can vary according to local regulations.
Common problems that occur with protocols include, being too ambitious, lack of
background knowledge, inadequate description of the study and its aim, poor justification,
inappropriate statistical analysis and lack of testing of the study methods and instruments.
When writing a protocol planning is essential, you should have a good understanding of
your funder’s policies, collaborator responsibilities should be clearly defined and it should
 be peer reviewed before being finalised.

References and Resources

1. Bowling A. Research Methods in Health: Investigating Health and Health
Services 3rd ed. 2009, Open University Press, Berkshire.
2. Fedor CA, Cola PA, Pierre C. Responsible research: a guide for coordinators
2006, Remedica, London.
3. Fitzpatrick S. The Institute of Clinical Research ‘Clinical Trial Protocol’
handbook 2006, Buckinghamshire, ICR Publishing.
4. Gravetter FJ, and Wallnau LB. Statistics for the Behavioural Sciences 7th ed.
2008, Thomson, Belmont.
5. Hackshaw A. A Concise Guide to Clinical Trials 2009, Wiley-Blackwell,
Chichester.
6. Hanson B. The art of choosing sound study endpoints 2008. Vol. 39, 6:656-658.
7. Hawkins JW, Haggerty LA (Eds.). Diversity in Health Care Research: Strategies
for Multisite, Multidisciplinary, and Multicultural Projects 2003, New York,
Springer.
8. Hennink M, Hutter I, Bailey A. Qualitative Research Methods 2011, Sage
Publications, London.
9. Hulley SB, Cummings SR, Browner WS, Grady DG, Newman TB. Designing Clinical Research
3rd ed. 2007, Lippincott Williams & Wilkins, Philadelphia.
10. Jadad, AR and Enkin M. Controlled Trials: Questions, Answers and Musings 2nd ed. 2007,
Blackwell Publishing, Massachusetts.
11. Jekel JF. Epidemiology, Biostatistics and Preventive Medicine 2007, Saunders, Philadelphia.
12. Laxer et al. A Open Label Study of a Flexible Dose of Brivaracetam in Subjects 16 Years or
Older Suffering From Epilepsy – trial ongoing
13. McFadden E. Management of data in clinical trials 2nd ed. 2007, Wiley & Sons Inc., New
Jersey.
14. Mulay M. A Step-by-Steve Guide to Clinical Trials 2001, Jones & Bartlett, London.
15. O'Brien K and Wright J. How to write a protocol. Journal of Orthodontics 2002, Vol. 29, 1:
58-61.
16. Saks M and Allsop J. Researching Health: Qualitative, Quantitative and Mixed Methods 2007,
Sage, London.
17. Silverman D. Doing Qualitative Research 3rd ed. 2010, Sage Publications, London.
18. Toto RD and McPhaul MJ. Clinical Research: From Proposal to Implementation
2011, Lippincott Williams & Wilkins, Philadelphia.
19. The EU Directive for Clinical Trials 2001/20/EC3.

Websites:

1. The WHO's Research Ethics

2. The Clinical Trial Registry

Resources

1. Free resources for conducting trials in developing countries

2. ICH Good Clinical Practice Guidelines
3. CIOMS Guidelines 2002
4. Declaration of Helsinki 2013
5. Global Health Glossary
6. Protocol Guide (MRC, Gambia)
7. Protocol Template (MRC, Gambia)
8. Trial Protocol Tool
9. WHO/TDR Guidance for Developing a Research Protocol
10. WHO 2002 Handbook for Good Clinical Practice
11. WHO 2005 Draft Guidelines for Adverse Event Reporting and Learning Systems
12. Zotero reference and bibliography tool: http://www.zotero.org/
13. Examples of consent form templates
14. SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) is an
international initiative that aims to improve the quality of clinical trial protocols by defining
an evidence-based set of items to address in a protocol

Quiz

Summary
1. Once a protocol is finalised it should not be altered under any circumstance:
True
False
2. Which of the following statements is false:
You should avoid trying to answer too many questions
It is important to be aware previous research in your topic of interest
An inadequate description of the proposed study and its aim lends to a poor
protocol
Poor justification for the study will result in failure to obtain funding and regulatory
approvals
Piloting or testing study methods and instruments is considered to be a waste of
resources.
3. When writing a protocol which of the following do you not need to consider:
The length of time required to prepare and finalise a protocol
The types of contracts required for the research team
Providing a sound background to the study
Including the tasks and responsibilities of all partners
4. Generating dummy tables can help you to decide on how many participants you need to
recruit:
True
False
5. A strong research team is one that:
Has a lot of time to spend on the study
Consists of experienced individuals with different areas of relevant expertise
Is not expensive to employ
6. To avoid wasting resources such as participant time and study funds it is important to
collect only data required to answer the study objectives:
True
False
7. Long term studies or those that plan to have participant follow-up should not use which of
the following to encourage continued participation:
Newsletters
Meetings
Monetary bribes
Merchandise
8. Which of the following statements is false:
High data quality is essential because the poorer the quality of your data the less
reliable the study results will be.
It is important to get the processes and procedures for data collection correct from
the start, as later on there is little you can do to improve the data quality.
Well-designed data capture forms (DCFs) mean that you will still have valid results
even if you are missing a lot of data
9. Funding bodies and health care decision-makers are interested in economic evaluations
because:
They can decide on where they would like the study to be run based on how much
it would cost
 They require information on both the effectiveness of the particular intervention,
and on its effectiveness relative to other interventions that already exist.
10. Which of the following is not a component of a well-designed DCF:
Clear and easy to read
Understandable instructions making it easy to complete
Collects additional information that might be useful for extra analysis
11. With clinical laboratory samples, labelling, tracking and management is very important
because:
Often the laboratory samples measure a critical endpoint in the study
Taking and processing samples is expensive so you don't want to lose any
12. When deciding upon your data management systems, which of the following does not have
to be considered:
Time needed to complete the DCF
Collection and entry
The database to be used
Processing and coding
Validation and cleaning
Analysis
13. Which of the following statements is false:
Failure to disseminate the study results means the time, resources and
commitment invested will have been in vain as no one will get to learn from your
research.
You should only publish your results if you achieve a positive result.
14. Clear, comprehensive internal and external quality systems should be established to:
Demonstrate the strength of the study design
See that as many participants as possible are recruited as quickly as possible
Enable the investigator to carry out the study in as short a timeframe as possible
Ensure that the quality of the study procedures, and the results generated, are
reliable and valid
15. Stopping rules can be put in place in case of:
Evidence of unacceptable risk or actual harm uncovered by interim analysis
The study running out of money
Participants withdrawing their consent to continue in the study
New regulatory approvals being required
16. Which of the following statements is true:
All adverse events must be reported to the ethics committee, even if they are only
minor
It will depend on the individual study which types of adverse events are reported,
by whom and within which timeframe
Only serious adverse events that result in death need to be reported to the ethics
committee
17. The statistical analysis plan sets out how you will analysis your data:
True
False
18. Which of the following should not be included in the statistical analysis plan:
The assessment of treatment compliance, efficacy and safety
The quality assurance processes
The reasons for the sample size selected, the power of the study, the level of and
significance to be used
The procedures for accounting for any missing or spurious data etc
The statistical tests that will be used to test the hypotheses and how the data will
be analysed

Submit