Sponsor proposed a randomized, open-label, multi-centre, parallel-group study comparing the safety and efficacy of STUDY DRUG with Novolog in type 1 diabetes (T1D) patients. Patients taking Novolog and either Levimer or Lantus with an HbA1c of 6.5% to 10.0% are eligible for the trial. During the 4-week run-in period, patients will be titrated (if applicable) on Novolog and shifted from their current basal insulin to Lantus. Following the run-in period, patients will be randomized to either Novolog or STUDY DRUG for 24-weeks.

During the run-in period, patients are required to self monitor blood glucose values (including date/time), insulin doses, hypoglycemic events and other data. The investigator will review these data and adjust insulin doses according to the insulin titration algorithm (and based on clinical judgement). The sponsor, CRO and possibly an independent insulin titration committee are to oversee insulin adjustments and compliance with the algorithm. Four study visits are planned during the run-in period, two of which could be conducted as a phone visit.

The sponsor proposed the use of paper diaries to collect patient reported outcomes during the run-in period and rest of study.

Type 1 diabetes is a complex condition for patients to manage. It requires monitoring blood glucose values (date/time/ value), insulin dosing, and tracking meal intake (carbohydrates), all with the goal to avoid hypoglycaemia. Participation in a clinical trial adds to this burden. In addition to managing their usual routine, patients are commonly asked to provide additional outcomes and other data to adhere to the study requirements. It can be difficult for patients to remember to report all that is requested (and when requested), which can increase patient angst and impact study compliance.

Paper diaries have often been used in diabetes studies to collect self monitored blood glucose values (fasting/pre- or post meals and/or 5-7-9 point scales), insulin dosing/adjustments, hypoglycaemia and other data. This adds burden to the patient in a clinical trial because patients have to remember to complete the diaries and return them at each study visit. For example, when collecting 7-point glucose data, patients are to measure and record their glucose value/date/time at 7 specified times points in a single day.

Based on ICON’s collective experience (corporate and personnel) with paper diaries, incomplete or missing data is common, patients often forget (inadvertently) to return the diaries at study visits leading to a delay in retrieval, and then once received, sites need to manually enter the data collected into the EDC (requested within 5 to 7 days but usually longer). Further these data need to be SDV which can be time consuming for the monitor. Consequently, this approach leads to a significant number of protocol violations and a lag in entry of data into the EDC for monitoring patient safety.

In consideration of the proposed study and the need for monitoring of the insulin titration algorithm during the run-in period, ICON felt that use of paper diaries would result in a delay in obtaining and entering data, making it challenging to provide timely oversight to ensure compliance and patient safety. Therefore, ICON proposed a fully integrated eCOA solution as an alternative, more efficient and less burdensome process.

ICON proposed a fully integrated eCOA solution supported by CRF Health to electronically capture the data that was to be collected in the paper diary, in particular, the self monitored blood glucose values/date/time, insulin dosages, and hypoglycemic events.

The system consists of 1) a hand held device (aka eDiary), 2) a Bluetooth enabled wireless glucose meter (My GlucoHealth) which allows data transfer to the eDiary and 3) a site management software tool.

The home based eDiaries are integrated with the glucometer allowing for automatic capture of glucose readings (Figure 1). The eDiary can indicate tasks that have been completed on a given day and what remains outstanding. Alerts can be set to notify the patient. Insulin doses can be recorded and adjustments to the insulin regimen can be transmitted from the site to the patient via the eDiary. Hypoglycemic event data also can be captured.
 

This approach does require more up-front planning and set up time than use of a paper diary. Transmission of data from the glucometer and/or eDiary can be interrupted if the subject’s home is in an area of low data network connectivity but to minimize this potential a back up mifi router can also be provided to allow the eDiary to automatically connect to and transfer data over either a 3 or 4G network. As standard, the eDiary automatically sends data to CRF Health’s central servers anytime a form is saved in the device and once a day during 3 to 4 am. This frequency can be increased dependant on the monitoring requirements of the project.

From a cost perspective, this fully integrated solution is more expensive (1.6M) than use of a paper diary at the present time; however, with the increased uptake of electronic solutions and continued efficiencies gained with implementations, cost reductions would be expected. In addition, financial comparison of these approaches (paper vs electronic diary) is a bit like comparing apples to oranges. The price of better quality data and reducing patient burden is hard to fiscally quantify. In addition, it is anticipated that this fully integrated eCOA solution will also be able to integrate data from a continuous blood glucose monitoring (CGM) device.