From: Farida Dabouz [mailto:[log in to unmask]]
Sent: August 17, 2009 11:50 AM
To: 'Ndema Habib'; [log in to unmask]
Subject: RE: Randomization problem
Dear Dr Habib,
Scenario 1:
participant 1 was randomized and not treated, and discontinued ( withdrew
consent) after randomization. This patient should be considered in the
Intent to treat (ITT) population (includes all randomized patients), and
depending on what was defined in the Statistical Analysis Plan (SAP), you
might have a modified ITT based on randomized patient receiving the implant
or not.
Participant 2 should have received another randomization envelop car the
opened one was already allocated to participant 1, unless your protocol
specified that earlier withdrawal can be replaced if the device not
used...(with more details on how this process should be done). Also because
the blind was broken, this is a major protocol violation. The participant 2
should be included in the ITT in the randomization group that he/she should
have been randomized, but then excluded from the modified ITT (if any ) and
from the per-protocol population(PP).
Scenario 2:
Yes we can keep the 2 patients in the ITT but analyzed in the allocated
randomization group that they should have received, but analyzed in the PP
population in the received randomization group, unless they will be excluded
from the PP due to randomization errors (this depends on the definition of
your per protocol population in the SAP.
Hope this respond to your questions. Randomization and blinding are very
important to be understood by investigators to avoid issues like that, which
can have an impact on the analysis, then on the power.
Good luck
Best regards
Farida Dabouz, PhD
FB2D Clinical Research Consulting
Montreal (Quebec), Canada
': 1 514-892-6451
7: 1 514-685-0632
8: <mailto:[log in to unmask]>
[log in to unmask]
www.FB2DConsulting.com
-----Original Message-----
From: A UK-based worldwide e-mail broadcast system mailing list
[mailto:[log in to unmask]] On Behalf Of Ndema Habib
Sent: August 17, 2009 11:11 AM
To: [log in to unmask]
Subject: Randomization problem
Dear allstaters and experts in randomization,
Please advise on the following two scenario in a randomized trial to what
issues should be considered:
First scenario-
During randomization visit, an eligible participant is given a randomization
envelop containing the details of the treatment (implant device) she would
be allocated to. This participant changes her mind (refusing to
participate) right after opening the envelop (she may have read what
treatment she is assigned) and she never received any treatment.
The trial investigator gives this same opened randomization envelop to the
next participant who is coming for randomization. this second participant
received the actual treatment (intended for the previous particip.) and
continues her follow-up and the problem about randomization irregularieties
is only discovered later during follow-up.
Question: Can we say participant 1 was discontinued before randomization
since she never actually received any treatment?
What about participant 2, should she be excluded from analysis because the
investigators knew the treatment she was going to receive prior to
randomization contrary to the protocol?
Second scenario-
two participants are each given an envelop containing one of two treatment
(implant devices) randomly allocated to them. Accidentally the actual
treatments are switched, so that each of the two participants despite being
assigned one treatment, she actually receive the one intended for the other.
this problem is discovered later on during followup.
Question: Can they be kept in the analysis and analysed according to
intention to treat? Are there ethical issues to be considered, as they did
not receive the treatments they thought they were on?
I'd appreciate any responses,
Thanks
Dr Habib.
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