Code break is also known as breaking the blind and involves un-blinding a participant so that the treatment allocation is made known.

Transcription

1

2 1. INTRODUCTION This SOP has been produced in accordance with Medicines for Human Use (Clinical Trials) Regulations This SOP will outline the procedure for breaking the study code in a NUH sponsored blinded randomised clinical trial of an investigational medicinal product (CTIMP). Clinical trials are often blinded to prevent the unintentional biases of either the patient or the investigator affecting subject data. Blinded studies, unlike open-label studies (in which treatment assignment is known), hide treatment group assignment from participants in the study. Code break procedures must be clearly established to ensure that no unnecessary or unintentional un-blinding occurs and to protect the integrity and validity of the data. If un-binding of participants is allowed during the conduct of a clinical trial other than for an emergency situation, the protocol must state the procedures for obtaining permission to break the blind. 2. SCOPE Code break is also known as breaking the blind and involves un-blinding a participant so that the treatment allocation is made known. Procedure 2.1 For NUH Sponsored IMP blinded studies the designated Clinical Trials Pharmacist holds the study codes in a study specific file. The study file is held in a secure area in Pharmacy with access only provided to those persons whom permission has been delegated. This permission is documented on the delegation list on a study by study basis. 2.2 A process for un-blinding and reporting without un-blinding the investigator in order to maintain clinical trial integrity should be in place. 2.3 No member of the investigating team will un-blind a subject or be notified of the result of un-blinding for the purpose of assessing an SAE. 2.4 Systems for SUSAR reporting should as far as possible maintain blinding of individual clinicians and of trial staff involved in the day-to-day conduct of the trial. 3. For blinded trials involving both a placebo and an active drug SOP 9 Unblinding Procedures for NUH Sponsored IMP Clinical Trials Page 2

3 3.1 The investigator should evaluate SAEs for causality and expectedness as though the patient was on the active drug. 3.2 Only cases that are considered serious, unexpected and possibly, probably or definitely related (like a SUSAR) would have to be un-blinded for reporting to the competent authorities. The subject should be un-blinded by either: (a) individuals who are not directly involved in the management of the specific clinical trial or any trial of active drug, or by (b) members of the Data Monitoring Committee (DMC). A DMC will have access to semi-blinded or unblinded data and can oversee the assessment of emerging risks such as increase in severity or frequency of expected events. 4. Blinded Trials involving two active drugs 4.1 The investigator making the assessment might be able to state that if the patient were on drug A, the event would be causal and/or expected but if on drug B would be expected. If the event were unexpected for either one of the active drugs, the case should be un-blinded by either: (a) individuals who are not directly involved in the management of the specific clinical trial or any trial of two active drugs, or (b) members of the DMC. A DMC will have access to semi-blinded or unblended data and can oversee the assessment of emerging risks such as increase in severity or frequency of expected events. The committee s assessments should be carried out without disclosure to the trial team. They may recommend protocol amendments or the termination of the study should they detect serious safety issues. 5. Breaking the Blind in an emergency 5.1 The CI/PI or treating physician contacts the holder of the code break envelope/list. During office hours the designated Clinical Trials Pharmacist should be contacted by phone. Out of hours, the on-call pharmacist should be contacted via switchboard (or as local policy). 5.2 The Clinical Trials Pharmacist (or delegate) provides the CI/PI or treating physician with the information as requested. 5.3 The study code should only be broken when absolutely necessary for valid medical or safety reasons e.g. in the case of a severe adverse event where it is necessary for the CI/PI or treating physician to know which treatment the patient is receiving before the participant can be treated. SOP 9 Unblinding Procedures for NUH Sponsored IMP Clinical Trials Page 3

4 5.4 The CI/PI documents the breaking of the codes as per protocol in the site file. 5.5 On receipt of the treatment allocation details, the CI/PI or treating physician deals with the participant s medical emergency as appropriate. 5.6 If the treating physician is not the CI/PI, the treating physician must inform the CI/PI of the code break and the reasons for the actions taken as soon as possible. 5.7 The CI/PI documents the breaking of the code and the reasons for doing so on the CRF and in the site file. 5.8 The Clinical Trials Pharmacist (or delegate) documents the breaking of the code and the reasons for doing so on the code list within the Pharmacy study file. 5.9 The CI/PI notifies by (RDSAE@nuh.nhs.uk) the Research and Development Department in writing as soon as possible following the code break detailing the necessity of the code break and copies to the Chief Investigator The CI/PI notifies the Research Ethics Committee of the protocol deviation and copies the letter to the Research and Development Department Un-blinded SUSARs will be reported to the MHRA and the REC by the NUH R&D department without disclosure to the trial team. 6. Information required 6.1 In the event of un-blinding (whether accidental or deliberate) the CI/PI must document the action taken and promptly notify the NUH. Notification must include: Name and title of person who requested the code break Subject number Reason for un-blinding Date and time of code break Name of person authorising the procedure Signature of person performing the un-blinding. 7. Breaking the blind at the end of the study 7.1 Un-blinding post study should not take place without good reason (e.g. ethical issues, patient safety). The un-blinding of participants cannot occur until all participants have completed the final data collection visit (also known as Last Patient Last Visit, LPLV). 7.2 Un-blinding should not take place until the database has been locked i.e. all data entered, validated and no further changes are expected. 7.3 Furthermore, it is best practice for the person performing the statistical analysis to remain blinded until after the analysis has been completed. 7.4 CI/PI contacts the Research and Development Department. NUH confirms that the study may be un-blinded by to the CI, copying in the designated Clinical Trials Pharmacist (or delegate). SOP 9 Unblinding Procedures for NUH Sponsored IMP Clinical Trials Page 4

5 7.5 The designated Pharmacy Clinical Trials Manager (or delegate) provides treatment allocation details to the CI as requested. 7.6 If necessary, (e.g. for safety reasons) the CI/PIs should make every effort to inform all-participants of their individual treatment assignment. 7.7 The CI/PI determines the appropriate method of informing participants of the blinded random assignment. If disclosure of the random assignment requires counselling of the participant or could cause distress, the PI (or delegate) does this in person. SOP REVIEW PERIOD This procedure will be reviewed by the owner on a biennial basis, unless new local, national and/or international recommendations force an earlier review. SOP 9 Unblinding Procedures for NUH Sponsored IMP Clinical Trials Page 5

6 Unblinding summary Serious adverse reaction Assess expectedness EXPECTED UNEXPECTED 1 DO NOT EXPEDITE Break blind Test product(s) Comparator(s) Placebo EXPEDITE 2 Assess expectedness for comparator product EXPEDITE (if reaction to component of placebo) EXPECTED UNEXPECTED DO NOT EXPEDITE EXPEDITE 2 1 for any of the test products administered to that subject 2 If the reaction is unexpected for the actual test or comparator product administered to that trial subject SOP 9 Unblinding Procedures for NUH Sponsored IMP Clinical Trials Page 6