Summary:
Randomized, double-blind clinical trials are the gold standard for adequate and well-controlled studies in modern times. However, prior to the late 1940s, randomization and blinding were not used in medicine and as result, bias was common. For example, treatment bias was often observed as physicians would treat sicker patients with known controls, while seemingly stronger patients would receive experimental products. Further, when not blinded, knowledge of a patient’s treatment regimen tended to affect the level of care a healthcare worker may provide and also influenced their observations regarding improvement, adverse events and other factors.
Overview:
By the early 1990s, biopharma companies and contract research organizations (CROs) began using technology more frequently and as a result, new methods of randomization could be used that promised to preserve study treatment balance, maintain the blind to avoid bias, minimize wasted medication and greatly improve the clinical supply chain. Interactive Voice Response (IVR) and later, Interactive Web Response (IWR) systems brought many new advances to the field of Randomization and Trial Supply Management (RTSM). Today such systems are generally referred to as Interactive Response Technology (IRT) systems and have user interfaces on the web via PC, tablet, phone and similar devices.
An important advantage of IRT is a more efficient supply chain. In the example of a six-month study cited earlier, suppose each patient visits the site once per month. Instead of sending six months of medication per patient to each site, only one or two visits worth per patient could be supplied initially. When a patient is randomized via the IRT, the investigative staffs are told the pack number to give the patient for that visit. For subsequent visits, the system knows which visit packs at the site will be valid for the patient and again, tells the staff which pack to dispense. Thus, if a patient discontinues early, hardly any drug is wasted as the remaining packs at the site can still be used by other patients on the same regimen.
Randomization is a key element in the success of a trial. An effective randomization plan built into an IRT system forms the basis of an adequate and well-controlled trial that is free of bias, maintains the study blind and ensures that the desired balance and treatment allocation ratios are preserved throughout the trial. Modern systems and simulation techniques are in place that have also greatly reduced the timelines to implement an IRT system while also providing high quality, reusable algorithms with a greatly reduced validation effort. Finally, there is no replacement for a qualified and experienced team who can provide guidance on all the critical factors involved in running a successful trial.
