Study Title
TRIAL MANAGEMENT PROTOCOLDATE dd/mm/yy
CHIEF INVESTIGATOR
List InvestigatorsInvestigation Sites:
Principle Investigators:
Protocol Identification Number: P00xxx
Date of Protocol:
Protocol Version Number
Trial Sponsor:
Protocol1.doc Page 1 of 22
Review Date:XXXX
C:\WINDOWS\TEMP\Protocol1.doc Issue Date:xx/xx/04
Contents
TRIAL OVERVIEW
1a. Trial Overview 5
Primary Research Question
Study Design
Primary Outcome
Secondary Outcome
Rationale
Schedule of Events 13
1b. Roles, Responsibilities 6-8
Team Members
Trial Steering Committee
Data Monitoring Committee
TRIAL MANAGEMENT GUIDELINES
2. Patient Recruitment 10
Study Population
Inclusion Criteria
Exclusion Criteria
Recruitment Strategy
3. Referral of Patients (if appropriate) 11
4. Consent Process and Visit Schedule 12
Visit 1
Follow-up Visit
Informed Consent Procedure 12
Tissue Storage 13
Table 2: Visit Schedule 13
Table 3: Trial Specific Procedures versus Routine Procedures 13
5. Randomisation 14
Procedure
Pharmacy Documentation and UnBlinding
6. Study Specific Chapters (No. pages and subsequent chapters accordingly) 15
8. Follow up Visits and Travel Expenses
9. Data Collection and Auditing
Data Collection Form Completion
Source Documentation
Errors and Correcting
Storage of Documents
Retention of Documents
Monitoring and Auditing
Labelling of Source Documentation
10. Adverse and Serious Adverse Events
Recording & Reporting
11. Data Analysis and Document Retention
Statistical Analysis
Economical Analysis
Retention of Documents
12. Amendments
Amendment log
13. Table 4: List of Essential Documents
14. Study Site File Containing Essential Documents
TRIAL OVERVIEW
1a. Trial Overview
Primary Research Question
Study Design
This section should include:
a. A description of the type/design of trial to be conducted e.g. twelve week, multi-centre, double-blind, randomised, placebo controlled, parallel design
b. Description of the study population e.g. Males with moderate to severe asthma
c. The expected duration of subject participation
Primary Outcome
State primary outcome
Secondary Outcome(s)
State secondary outcome(s)
Rationale
Provide details of the background and reasons for conducting the study
Schedule of Events
1b. Roles & Responsibilities
Team Members
§ Investigators
§ A Chief Investigator has overall responsibility for a multi-site study
§ A Principal Investigator takes responsibility for a study at a single site
- As stated in ICH GCP (1996) an investigator should be qualified by education, training and experience to assume responsibility for the proper conduct of the study. He/she should meet all the qualification specified by the appropriate applicable regulatory requirements and should provide evidence of such qualifications through up-to date curricula vitae (CVs should not be more than 2 years old).
- Takes responsibility for compliance with all legal and ethical requirements.
- The investigator should be thoroughly familiar with the appropriate use of the investigational product as stated in the protocol. The investigator should also ensure that Clinical Research Nurse/Assistant and all personnel are fully informed about the protocol, investigational product/procedure and follow the protocol accurately.
- The Investigator should:
o Be able to demonstrate the potential to recruit the required number of clinical study subjects
o Have sufficient time to conduct and complete the study within the required time period
o Have adequate facilities and staff to conduct the study properly
- The Investigator is responsible for:
o The welfare of the patients
o Obtaining informed consent
o Prescribing drugs
o Conducting clinical examinations and reviewing test results
o Ensure that all Ethics Committee, Trust and MHRA requirements are met
o Ensure all protocol, participants’ information sheet amendments are approved by Ethics
§ Clinical Research Nurses/Assistants
- Conducts research in accordance with the agreed protocol and ICH GCP.
- Recruits and screens participants.
- Informs participants about the study and takes written informed consent.
- Ensures participants’ welfare whilst in the study.
- Collects and records the research data.
- Maintains trial specific paperwork i.e. regulatory applications and approvals, data collection forms.
- Documents adverse events and informs the Investigator, ethics and R&D of any serious adverse events.
- Updates screening and recruitment logs.
- In conjunction with the Investigator, ensures that all study team members and referring hospital personnel are fully informed about the study.
- Attends multidisciplinary meetings/research meetings.
- Liaises with appropriate specialist nurse regarding trial participants.
§ Research Officer
- Monitors that the research study is compliant with the Research Governance Framework and ICH GCP.
- Advises on protocol and data collection sheet design.
- Monitors Ethics and Trust approvals for the protocol, information sheets and all amendments.
- Monitors timelines relating to study start up, recruitment and final reports.
- Attends team meetings and ensures that agendas and minutes are written and distributed in a timely manner.
- Monitors all collected data at monthly intervals throughout the study.
- Co-ordinates, attends and minutes the Data Monitoring Committee meetings.
- Line-manages/supervises the Clinical Research Nurses and ensures that their responsibilities are conducted to a high standard and they have adequate support and training.
- Informs service manager of the research study and any implications for service provision.
- Monitors and alerts the study team to the requirements of reports to the funding agency and research ethics committee.
§ Statistician
- Advises on the design of the study, power calculations and randomisation procedure.
- Checks the quality of the data at intervals throughout the study.
- Analyses the data.
- Interprets the results of the statistical analysis.
- Advises the Investigator on the preparation of reports and submissions to journals.
§ Service Manager
- Ensures that research study does not impact on routine service provision.
- Attends team meetings to advise on service implications.
Trial Steering Committee (see Table 1)
- Provides overall supervision of the trial.
- Monitors the progress of the trial, adherence to protocol.
- Considers the rights, safety and well-being of the trial participants.
- Monitors and supervises the progress of the trial towards its overall objectives
- Reviews at regular intervals relevant information from other sources (e.g. other related trials).
- Considers the recommendations of the Ethics Committee.
- To meet at least once a year.
- The membership should be limited and include an independent Chairman (not involved in the trial other than as a member of the TSC), not less than two other independent members and one or two Principle Investigators. Where possible a lay/consumer representative.
- Trial co-ordinators, statisticians etc should attend meetings as appropriate.
Data Monitoring Committee
- The role of the DMC is to look at the data from an ethical standpoint, the safety, rights and well being of the study participants.
- The member ship of the DMC will usually be small: 3-4 members who are independent of the study, and will consist of an expert statistician and experts in the field (e.g. clinician with experience in the relevant area.
- Determines if additional interim analyses of trial data should be undertaken.
- Considers the data from the interim analyses, unblinded if considered appropriate, plus any additional safety issues for the study and relevant information from other sources.
- Reports to the Trial Steering Committee and advises on the continuation or extension of the study.
- Considers any requests for release of interim data and to recommend to the TSC on the advisability of this.
Table 1 Trial Steering Committee
Chairman
Statistician
Health Economist
e.g. Physician
e.g. Surgeon
TRIAL MANAGEMENT GUIDELINES
2. Patient Recruitment Criteria
Study Population
Provide details of
§ Patient/participant number
§ Population group
§ Recruitment period
Inclusion
§ List inclusion criteria
Exclusion
§ List exclusion criteria
Recruitment
§ Detail the recruitment strategy
§ The planned recruitment target rate is:
- Year 1: n patients
- Year 2: n patients
- Year 3: n patients
The recruitment rate has been calculated on (insert details of calculation method and evidence base e.g. retrospective data, estimated referral rate and drop out rate).
§ Insert a recruitment schedule spreadsheet.
§ Insert recruitment review dates.
§ Insert details of a recruitment promotion e.g. newsletters, websites.
§ Insert details of a strategy, if known, on boosting recruitment if recruitment targets are not being met.
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3. Referral of Patients
Insert details of the referral process if patients are being referred from other hospitals, GPs etc
§ The CRNs will visit each of the referring centres on a (insert time interval e.g quarterly) basis to review the referral procedure and to provide feedback on the progress of the study.
§ The research staff can claim either a mileage allowance for personal car use or public transport costs, or they can book the Papworth Hospital pool car. The pool car availability is on the hospital intranet and can be booked via Peter Chatfield on the Papworth e-mail or on extension 4662.
Protocol1.doc Version No: Page 22 of 22
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4. Consent Process and Visit Schedule
Visit 1
§ Enter details of where patients will be seen and the process for booking patients into a clinic, if appropriate.
Follow-Up Visits
§ Each patient will be assigned a study number by the Clinical Research Nurses; the study numbers will be allocated sequentially starting at 001. If a
§ patient fails screening the screening number must not be reused for a subsequent patient.
§ Visits should be scheduled and performed according to table 2.
§ Trial specific procedures versus routine procedures are detailed in table 3 if appropriate to the study. The trial specific procedures can only be performed after written informed consent has been obtained. The procedures that can be performed prior to consent being obtained are detailed in table 3 (if appropriate).
Informed Consent Procedure
§ Patients will receive written and verbal information about the trial
§ Written informed consent will be obtained by a member of the trial team after a suitable time has elapsed (at least 24 hours) during which the patient has had ample time to read the information sheet, consider the trial and ask any questions (Consent form, appendix x). The Investigator or the Clinical Research Nurse must explain to each patient the nature of the study, its purpose, the procedures involved, the expected duration, the potential risks and benefits involved and any discomfort it may entail (Ref. International Conference of Harmonisation of Good Clinical Practice (ICH/GCP)5 4.8.7
§ The ultimate responsibility for obtaining written informed consent lies with the Investigator but this responsibility may be delegated to a suitably trained, and experienced person.
§ Prior to the patient’s participation in the study, the written informed consent form must be signed and personally dated by the patient and by the clinician who conducted the informed consent discussion (Ref. ICH/GCP 4.8.8). Each box at the end of each statement on the consent form must be signed by the patient.
§ Each subject must be informed that participation in the study is voluntary and that he/she may withdraw from the study at any time and that withdrawal of consent will not affect his/her subsequent medical treatment (Ref. ICH/GCP 4.8.10).
§ A copy of the informed consent document will be given to the patient (Ref. ICH/GCP 4.8.11). One copy will be filed in the patient’s hospital case notes and a copy filed in the Trial Management File by the Clinical Research Nurses.
§ The Clinical Research Nurse will ensure that the patient does not have any trial specific procedures prior to giving informed consent.
§ If a patient withdraws their consent a line should be drawn diagonally through the consent form and labelled ‘consent withdrawn’ and signed and dated by a member of staff (please refer to Section 8 re labelling of case notes).
Consent for Tissue Storage (delete if not applicable)
§ Tissue which is obtained for the study can only be stored in the hospital tissue bank for use in future studies relating to future research if the patient has signed and dated a corresponding statement on the consent form.
§ A copy of the consent form for each patient who consents to tissue storage is to be sent to Jean Chadderton, Tissue Bank Co-ordinator, Pathology, Papworth Hospital, extension 4767.
Table 2 Visit Schedule
Visit Number
/ Visit n / Visit n+1 / Visit n+2 / Visit n+3 / Visit n+4 / Visit n+5Time interval of Visit / e.g. week -1 / e.g. week 0 / e.g. week 1
Consent / X
Medical History / X
Physical exam / X
Table 3 Trial Specific Procedures versus Routine Procedures
Routine Investigations / Study Specific ProceduresComplete if appropriate
5. Randomisation
Procedure
Patients who consent in writing to participate and fulfil the inclusion and exclusion criteria can be randomised.
The randomisation procedure will be performed by Papworth Hospital NHS Trust R & D Unit during office working hours (9am – 5pm) The Clinical Research Nurse/Assistant will contact the R&D department’s main office on extension 4143 or 4448. The following information will be required in order to proceed to randomisation:
§ Patient study number
§ Patient name
§ Hospital number
§ Date of birth
§ Add other details as required
A copy of the randomisation form will be faxed from the R&D office to a safe haven fax (state location and the fax number) where it will be collected and filed with the study documentation by the Clinical Research Nurse. The original will be filed by R & D in the R&D randomisation file.
(This arrangement will not apply to all studies. Therefore, insert the appropriate arrangements).
Pharmacy Documentation and Unblinding
The clinical trials pharmacist records the randomisation details onto a pharmacy randomisation log, which is held in pharmacy, of all patients randomised into the study.
In blinded studies, a patient’s randomisation group should only be unblinded/ revealed in the event of an emergency in which the Investigator or medical personnel believe that the subsequent medical management would be to the patient’s detriment if the nature of the study drug was unknown. To un-blind the study drug, the trial pharmacist would be contacted who would provide details of the study drug. If the process is required out of routine working hours the on-call pharmacist is to be contacted; he/she would have a copy of the randomisation log and instructions on how to break the code.