By Dr Steph Jones
Pharmora has many times been called upon to help with data review near the end of Phase III clinical trials, when the global study team find there is too much to do and their deadlines are at risk. Our clients have started to realise that partnering with Pharmora from the beginning of the study can save them money and help them achieve their goals without this resource peak at the end.
Pharmora provides a wide range of services in addition to this clinical development support, for example patient safety services including individual case review, routine safety surveillance and signal evaluations. Pharmora is therefore familiar with reviewing unblinded data, and with functioning as an independent team while maintaining the blind for other teams involved in the project.
Due to this range of expertise we can help with unblinded medical review (UMR) of data for clinical trials.
What is unblinded medical review (UMR)?
This is the review of data for a participant in a clinical trial with the knowledge of the treatment that participant was assigned to. There are several types of UMR:
– In double-blind randomised clinical trials no-one knows which treatments the patients are assigned to, and the data are entered by the Investigators in a blinded manner. In some situations it is important to unblind individual participants, for example when they have a medical emergency that requires knowledge of treatment assignment. The team may select an independent UMR team to oversee this process so that the rest of the study team can remain blinded.
– In “open label” studies the participant and Investigator both know which treatment is being used. In these situations the study team may wish to remain blinded, to allow them the ability to analyse the data without bias from the knowledge of treatment assignment. They need an independent team to help review the data to ensure accuracy so that they do not accidentally find out what the participants are being treated with, and to help monitor the safety of clinical trial participants.
Why is it important to maintain the blind in a clinical trial?
During clinical trials there are many data points that require judgment, for example causality assessment of adverse events, and decisions on efficacy endpoints to determine whether the treatment is working. It is important that the person making such judgments is not influenced by knowledge of which treatment was assigned to the participant.
Equally when performing an evaluation of the aggregated clinical trial data it is important that the statisticians select appropriate analyses and conduct these without being influenced by the knowledge of treatment assignments.
When do we need UMR?
Sometimes it is not possible to perform a completely double-blind study, particularly if there are differences in the dosing schedule or route of administration for the different treatments. For example, if the gold standard treatment is an intravenous injection, and we want to compare it to an oral investigational medication to assess efficacy, tolerability and demonstrate advantages such as ease of administration, we cannot use an intravenous placebo. The patient will therefore know which treatment they have been assigned to and it is impossible to blind the local Investigator.
The global study team can remain blinded in such situations. This is called “Sponsor-blinding”. However, the patients in such studies need to be monitored and the Investigator staff sometimes need guidance to help them enter the data accurately, or in the management of toxicities.
This is when UMR is needed. The UMR team needs to be fully independent, with expertise in the relevant therapy area, proficient in data review, and also skilled at maintaining the blind for the sponsor team.
Read our case study to find out how this works in Pharmora
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