June 2015
Code Breaking – who, what, when,
Outline
o What is blinding?
o Why are studies blinded? o What is code breaking?
o When would I want to code break? o Code breaking in the event of a SUSAR o Who can code break?
o Ways of code breaking
o After treatment has been unblinded o Out of hours arrangements
What is blinding?
Randomised Controlled Trials (RCT)
– A study in which participants are randomly assigned to a particular treatment group to test a specific drug or treatment. One group (the experimental group) receives the treatment being tested, the other (the comparison or control group) receives an alternative treatment, or a dummy treatment (placebo) or no treatment at all. The groups are followed up to see how effective the experimental treatment was. Outcomes are measured at specific times and any difference in response between the groups is assessed statistically. This method is also used to reduce bias. (nice.org.uk)
Usually phase III, some phase II Variety of cohorts
Types of blinding and study design
Single blind – Investigator – Subject/Patient
– Other medical professional e.g. Radiographer, physiotherapist Double blind
– Investigator and subject – Not always pharmacy Triple blind
– Until Safety issues Placebo controlled
Why are studies blinded?
To prevent bias
– Different cohorts, e.g. according to age, disease status, prior treatment Ensure that valid and reliable data are collected
Confidence in the findings Placebo effect / No-cebo Product licensing
Who is blinded and to what?
Investigator Sponsor Research Team Participant Study Monitor Pharmacy Other healthcare professionals e.g. radiographer, physiotherapist Treatment
What is code breaking?
Unblinding – Breaking the blind Revealing the subject’s treatment
…the coding system for the IMPs should include a mechanism that permits rapid identification of the products in the case of a medical emergency, but does not permit undetectable breaks of the blinding.
ICH GCP Section 5.13.4
ICH GCP
4.7 Randomisation Procedures and Unblinding
The investigator should follow the trial's randomisation procedures, if any, and should ensure that the code is broken only in accordance with the protocol. If the trial is blinded, the investigator should promptly document and explain to the sponsor any premature unblinding (e.g., accidental unblinding, unblinding due to a serious adverse event) of the investigational product(s).
When would I want to code break?
o In an emergency
o When knowledge of the subject’s treatment will affect how we treat them
Code Breaking in the event of a SUSAR
Suspected unexpected serious adverse reaction Patient safety
Report to Sponsor
European Commission guidelines (Eudralex Volume 10):
– assess, in view of the various reported SUSARs, whether an IMP poses an unknown risk to the subject, and
Who can code break?
According to the protocol
– Do you have to seek permission from the sponsor team first? Chief/Principal Investigator (CI/PI)
Research team members – nurses, coordinators, sub-investigators Pharmacy (CTIMPs)
HOW ?
o Permission obtained from PI & Sponsor?
o IVRS / IWRS
o Sealed envelopes
o Scratch cards
o Removable labels
After the treatment has been revealed
What treatment will the subject receive?
Who should be made aware of the treatment? – Keep team members blinded, if possible – Keep the subject blinded, if possible Report to sponsor
Out of hours arrangements
What plans do you have in place for out of hours code breaking?
– Consider individual study requirements – Likelihood of having to code break
Who has the ability to code break in your team/ department?
On-call services Pharmacy
Have you tested your code break procedures?
o Do the telephone numbers/web addresses work?
o What information will be required?
o Any SOPs/guidance in place?
o Protocol
o Departmental arrangements
o Pharmacy Procedures
o Pharmacy – Code break form (example found in your pack)
o
Have you activated your IVRS/IWRS account?
Have I ever had to code break?
Anastrazole/placebo in breast cancer
– Subjects that had completed the study and required further treatment years later. – The current guidance recommended the use of anastrazole treatment.
– If the subject had been randomised to anastrazole, an alternative treatment was required.
Monoclonal antibody – Death
Pitfalls of blinding & code breaking
o Investigator team unfamiliar with process or inadequate holiday/sickness cover in event of emergency code-break
o Team members & participants may guess the treatment
o Potential for accidental unblinding
o How easy is it to reveal treatment? o Unintentionally reveal treatment
o Who is looking at your study information?
Interesting links
Understanding controlled trials: Why are randomised controlled trials important? http://www.bmj.com/content/316/7126/201
Cancer Research UK http://www.cancerresearchuk.org/cancer-help/trials/types-of-trials/about-randomised-trials
European Commission – Volume 10 Clinical trials guidelines http://ec.europa.eu/health/documents/eudralex/vol-10/
MHRA- Adaptive Clinical Trial Design
http://www.ahppi.org.uk/cms/wp-content/uploads/2013/04/WS4-Adaptive-study-design-OKane.pdf
JREO Workshops
July – Medical Devices 12:30pm 22nd July Board Room H2.6
Training sessions will then restart in the new academic year **For full list , please visit our website**
https://portal.sgul.ac.uk/research/research-office/research-governance/Training
This and previous presentations will be available on the portal for your reference if you are interested in any of our training being provided specifically for your department
please get in touch
We are always contactable to answer queries and help you through the process Check out our ‘Guide for Researchers’?
https://portal.sgul.ac.uk/research/research-office/a-guide-for-researchers-v1-dec-2014
Good Clinical Practice (GCP) 8th July 2015 10am to 4pm
