Essential Documents

Question 1

What is the trial master file?

Answer 1

A file that contains all the essential documents relating to the clinical trial before it commences, during the trial conduct and after the trial

Question 2

Outline guidelines for the management of eTMFs

Answer 2

User acoounts 
Secure passwords 
System in place to prevent changes to documents 
Audit trail 
Regular back-up 
Role based permissions

Question 3

What are the benefits of using eTMF over paper versions?

Answer 3

Documents can be tracked and viewed in real time from any location
Contents easily identified and missing documents noticed
Can speed up start up time
Can speed up study close out
Can ease committee communication
Easier audit process

Disadvantage: more expensive

Question 4

List some examples of documentation needed to start a trial

Answer 4

Funding proposal 
Agreement from funder
Investigator brochure
SOPs
Statement about SAEs
Checklist for site-assessment 
Insurance certificate 
Ethics committee application/approval 
Scientific and governance approval 
Registration certificate/number 
Documentation about staffing 
Licence for import of drugs

Question 5

What scientific documents are needed at the start of the trial?

Answer 5

Protocol an sample case report form

Question 6

What are the main purposes of the trial protocol?

Answer 6

Helping with applications for funding
Applications for ethical and other governance approvals from the relevant committees
Guidance to investigators on the conduct of a trial
A source of information for those monitoring a trial
Providing the basis for the analysis and reporting of the trial

Question 7

List the general components of a trial protocol

Answer 7

General information
Background information
Trial objectives and purpose
Trial design
Selection and withdrawal of subjects
Treatment of subjects
Assessment of efficacy
Assessment of safety
Statistics
Direct access to source data/documents
Quality Control and Quality Assessment
Ethics
Data handling and record keeping
Finance and insurance
Publication policy
Supplements

Question 8

What is the purpose of publishing the trial protocol before the trial begins?

Answer 8

Provides and opportunity for peer-reviewed feedback

Reduce the liklehood for bias in reporting

Question 9

What is the case report form?

Answer 9

The ICH GCP guideline describes the Case Report form (CRF) as a printed, optical or electronic document designed to record all of the protocol required information

Question 10

What documents are needed at the start of the trial from an ethical standpoint?

Answer 10

Information given to trial participants

Documented approval of Research Ethics Committee

Question 11

What documents fall into the category of “information given to participants”?

Answer 11

Informed consent forms (including all translations)

Advertisements for subject recruitment (inc radio, video media etc.)

Question 12

Which guidelines tell us what participants need to know in order to give informed consent?

Answer 12

Declaration of Helsinki “International Ethical Guidelines for Health-Related Research Involving Humans”

Question 13

What features need to be included in the participant information documentation in order to gain valid and informed consent?

Answer 13

Overall aim of the study
Possible harms and benefits
What is expected of the trial participant (freq of visits and follow-up)
Upon reading the participant should not feel obliged or coerced into participation - it is entirely voluntary
Participant is free to withdraw without any prejudice to any future medical care

Question 14

Outline the steps required for translation of essential documents in clinical trials?

Answer 14

Official translation
Back translation (for accuracy)

Question 15

What documents are generally required at the start of a trial to manage said trial?

Answer 15

Agreement between sponsor and investigator
Financial aspects of the trial
Insurance arrangement

Question 16

Which committee may check any adverts used in clinical trials to ensure they are appropriate?

Answer 16

Ethics committees and community advisory boards (CABs)

Question 17

Reminder: what is the reason for using blinding procedures in clinical trials?

Answer 17

Reduce biases in assessment of outcomes and during the course of treatments

Question 18

Where are randomisation lists kept? Why?

Answer 18

Only held with the sponsor’s TMF and not in local ones - to ensure concealment

Question 19

What documentation about participants is required during recruitment?

Answer 19

Consent forms
Particiaptn identification code list
Participant enrolement log
Signed and dated case report forms

Question 20

How does a patient sign a consent form if they are illiterate?

Answer 20

THumb print

Question 21

What documents to do with patient recruitment are usually not disclosed to the sponsors and why?

Answer 21

Consent forms, indentification and enrollment list - because they contain patient information

Question 22

What documents are regularly sent to ethics committees as a trial proceeds?

Answer 22

6-monthly or yearly progress reports and safety data (Assessment of SAEs)

Question 23

What sort of reporting is required to be sent to regulatory authroties?

Answer 23

Safety reports (often called Development Safety Update Report Form (DSUR) - the CI must file the original with related acknowledgements and correspondence in the TMF

Question 24

What is the role of the site monitor?

Answer 24

Independent party to the personelle of the site under monitoring to ensure adherence to strict GCP, SOP and other regulatory requirements

Question 25

What are source documents?

Answer 25

Original documents, data and records e.g. hospital records, clinical and office charts etc.

Where data has been recorded first (as defined in the protocol)

Question 26

Typically what are the two different types of adverse events in a trial

Answer 26

Serious adverse effects and suspected unexpected adverse reactions

Question 27

What is the protocol for dealing with adverse events?

Answer 27

Report to necessary bodies (inc sponsor, CRO) in agreed timelines
Report to regulatory and ethics committees as defined in protocol

Question 28

What is CTIMPs?

Answer 28

clinical trial of investigational medical products - either a new unlicensed medication or a previously marketed medicine being pitched for a new indication

Question 29

What in general is defined as the end of the trial for documentation purposes?

Answer 29

The date when the final patient has their last visit

Question 30

Records must be kept securely after the trial has ended. Why do you think this is the case?

Answer 30

In case other studies suggest a further follow up period is indicated
There are allegations of fraud
There are any concerns about side effect and participants need to be notified

Question 31

What is the purpose of scientific peer-review?

Answer 31

To protect future participants
To avoid unnecessary duplication of research
TO avoid publication bias
To further scientific careers

Question 32

What additional documents are required at the end of a trial for an investigational product which are held by both the TMF and ISF?

Answer 32

Product accountablity documentation

Documentation of investigational product destruction (for surplus)

Question 33

What additional documents at the end of an investigational product trial are kept only with the TMF centrally?

Answer 33

Allocation and decoding documents
audit certifications
final close out monitoring reports

Question 34

How long should data be archived for?

Answer 34

If not kept for regulatory submission then approx. 5 years

If for regulatory submission then at least two years after the last approval of a marketing application in a ICH region

Question 35

How are archived documents eventually destroyed?

Answer 35

Record signed and kept by a person of significant authority for five years and then they willbe informed by their sponsor when they can destroy their records