Essential Documents Flashcards
What is the trial master file?
A file that contains all the essential documents relating to the clinical trial before it commences, during the trial conduct and after the trial
Outline guidelines for the management of eTMFs
User acoounts Secure passwords System in place to prevent changes to documents Audit trail Regular back-up Role based permissions
What are the benefits of using eTMF over paper versions?
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
List some examples of documentation needed to start a trial
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
What scientific documents are needed at the start of the trial?
Protocol an sample case report form
What are the main purposes of the trial protocol?
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
List the general components of a trial protocol
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
What is the purpose of publishing the trial protocol before the trial begins?
Provides and opportunity for peer-reviewed feedback
Reduce the liklehood for bias in reporting
What is the case report form?
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
What documents are needed at the start of the trial from an ethical standpoint?
Information given to trial participants
Documented approval of Research Ethics Committee
What documents fall into the category of “information given to participants”?
Informed consent forms (including all translations)
Advertisements for subject recruitment (inc radio, video media etc.)
Which guidelines tell us what participants need to know in order to give informed consent?
Declaration of Helsinki “International Ethical Guidelines for Health-Related Research Involving Humans”
What features need to be included in the participant information documentation in order to gain valid and informed consent?
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
Outline the steps required for translation of essential documents in clinical trials?
Official translation Back translation (for accuracy)
What documents are generally required at the start of a trial to manage said trial?
Agreement between sponsor and investigator
Financial aspects of the trial
Insurance arrangement
Which committee may check any adverts used in clinical trials to ensure they are appropriate?
Ethics committees and community advisory boards (CABs)
Reminder: what is the reason for using blinding procedures in clinical trials?
Reduce biases in assessment of outcomes and during the course of treatments
Where are randomisation lists kept? Why?
Only held with the sponsor’s TMF and not in local ones - to ensure concealment
What documentation about participants is required during recruitment?
Consent forms
Particiaptn identification code list
Participant enrolement log
Signed and dated case report forms
How does a patient sign a consent form if they are illiterate?
THumb print
What documents to do with patient recruitment are usually not disclosed to the sponsors and why?
Consent forms, indentification and enrollment list - because they contain patient information
What documents are regularly sent to ethics committees as a trial proceeds?
6-monthly or yearly progress reports and safety data (Assessment of SAEs)
What sort of reporting is required to be sent to regulatory authroties?
Safety reports (often called Development Safety Update Report Form (DSUR) - the CI must file the original with related acknowledgements and correspondence in the TMF
What is the role of the site monitor?
Independent party to the personelle of the site under monitoring to ensure adherence to strict GCP, SOP and other regulatory requirements
What are source documents?
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)
Typically what are the two different types of adverse events in a trial
Serious adverse effects and suspected unexpected adverse reactions
What is the protocol for dealing with adverse events?
Report to necessary bodies (inc sponsor, CRO) in agreed timelines
Report to regulatory and ethics committees as defined in protocol
What is CTIMPs?
clinical trial of investigational medical products - either a new unlicensed medication or a previously marketed medicine being pitched for a new indication
What in general is defined as the end of the trial for documentation purposes?
The date when the final patient has their last visit
Records must be kept securely after the trial has ended. Why do you think this is the case?
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
What is the purpose of scientific peer-review?
To protect future participants
To avoid unnecessary duplication of research
TO avoid publication bias
To further scientific careers
What additional documents are required at the end of a trial for an investigational product which are held by both the TMF and ISF?
Product accountablity documentation
Documentation of investigational product destruction (for surplus)
What additional documents at the end of an investigational product trial are kept only with the TMF centrally?
Allocation and decoding documents
audit certifications
final close out monitoring reports
How long should data be archived for?
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
How are archived documents eventually destroyed?
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
