For trials set-up for internet randomisation a Randomise link will be shown in the top menu bar or a Randomisation form will be present in the CRF. Either route takes the user to the randomisation form that requests relevant subject information needed to perform the randomisation. The form will vary depending on the trial; each trial is individually configured. Administrative users may see a field to select the site the subject originates from. Investigators can only randomise for the site they are associated with and so will not see this option.
Once the form has been completed and submitted the user will be asked to review the information they entered and check it is correct. They can return to the previous screen to change items if any are incorrect. To continue, and generate a randomised allocation, the user must enter their password and click on the Confirm button. If the randomisation succeeds the user will be shown the randomisation code on-screen. For unblinded trials the code shown is the actual treatment group. Some trials may display multiple codes (for example where the amount of drug to be given depends on a subject’s weight).
Result of randomising a subject in an unblinded trial
Randomisation may not succeed for trials with code lists if no randomisation codes are available for the site concerned. Depending on trial configuration, randomisation may also fail if a subject with the same details has previously been randomised (duplicate).
For trials set-up for telephone randomisation the user may randomise a subject using a touch-tone telephone by calling the trial specific telephone number. After authentication, the user will be asked a series of questions to collect stratification information and check eligibility. Once all information has been collected the randomisation will take place and the randomised group or code will be announced to the caller. Telephone randomisations can be viewed in the online system in the same way as randomisations carried out online.
An email containing the randomisation code will be automatically sent out to all relevant users that have notifications enabled. Relevant users are trial administrators and all investigators associated with the site that the randomisation originates from. Notifications are not sent to users with suspended accounts. Administrators can see the format of notification emails on the specification page.
Occasionally, it may be necessary to randomise a subject outside the randomisation system using an emergency procedure, such as giving the next treatment allocation from a pre-defined backup list. This is called a manual randomisation. To record the details of manual randomisations in the system an administrator should click the Enter manual randomisation details link at the bottom of the randomisation form. This will reveal extra fields: date and time of randomisation, and randomisation group or code. For blinded trials with a code list the code entered must match an unused code in the code list. However, no other validation is performed on the code: expiry date (if set) and site where the code is available are not checked. Once the form is saved the randomisation is recorded and clearly marked as a manual randomisation. If your trial uses minimisation for balancing treatment groups, then manual randomisations will be taken into account for future randomisations.
A randomisation limit is enforced that prevents further randomisations taking place once the limit is reached. The limit can be seen on the specification page. Randomisations marked as in error do not count towards the limit.
Some randomisation methods rely on a predefined randomisation list, whereas dynamic methods (such as minimisation) do not use a randomisation list. The randomisation method is shown on the specification page. The total number of unused allocations in the randomisation list will be displayed if applicable, and a report, Allocations available in the randomisation list, will show the number of used and available allocations by the levels of each strata. Randomisation will not be possible if there are no allocations available for the stratification factors that apply to the subject being randomised. Contact Sealed Envelope support if this happens as it will be necessary to extend the randomisation list.
An error due to lack of allocations in the randomisation list
If an administrator has disabled randomisation it will not be possible to add a new randomisation form. The exception is that administrators can still record manual randomisations. Existing randomisation forms remain accessible for viewing and editing.
The randomisation form behaves in the same way as other Red Pill forms with a few exceptions. Firstly, validation overrides are not enabled so that any errors in data-entry must be resolved before proceeding. Secondly, the review step is never disabled for the randomisation form, even if it is disabled for other forms in a Red Pill application.