User Power: Managing Cohorts

Case Studies

The Problem:

The management of multiple cohorts is a standard offering of most IRTs. In the common sequential model, when Cohort 1 reaches a pre-designated limit the cohort is closed by the system and subjects can no longer be enrolled into that cohort. Problem: The design of your study is such that the maximum number of subjects in each of your four planned cohorts cannot be fixed at study startup, and more than one cohort can, in certain circumstances, be open simultaneously. How should the IRT be set up to provide this kind of adaptability?

The Veracity Logic Solution:

A typical approach to achieving flexible cohort functionality is to assign the task to the system development team. Programmers and configuration managers would modify code or system configurations during the trial as needed to adjust cohort parameters. Additional costs, time delays, and the need to produce change orders and approval documents for interparty communication, are three notable downsides to this approach.

Veracity Logic’s IRT platform supports an alternate strategy. In addition to system controls, we offer a user-friendly, manual approach that puts the power of change directly into the hands of authorized users. Cohort parameters are configurable, no coding changes required. Cohort limits can easily be modified and re-modified with the click of a button. Likewise, cohorts can be manually opened and closed, re-opened and re-closed on demand, all by the users themselves, and in the users’ own timeframes.

Dynamic Randomization — Striking a Balance

Case Studies

The Problem:

Randomization — that is, the truly random assignment of patients to a treatment group in a clinical trial — is the gold standard approach to producing statistically valid results in drug studies. Randomization is intended to eliminate bias — theoretically, the myriad of variable and potential variable differences between patients, both known and unknown, should even out over time in infinitely large samples. But study sample sizes in the real world are not infinite. In many cases, they’re not even what one would call ‘large,’ mathematically speaking. In real life scenarios, such as new drug trials, a study can wind up having a serious imbalance in prognostic factors and assignment to study treatment groups. Serious enough, in some cases, that imbalances can call study results into question.

The Solution:

Dynamic Randomization is an alternate strategy in the biostatistician’s toolbox. In a dynamic approach, there is no pre-existing randomization schedule as there is for studies using static randomization designs. Rather, the randomization table is dynamically built as the study proceeds. For each new patient to be randomized into the study, the IRT algorithm takes into account the balance/imbalance that will result from the assignment of the new patient to each treatment group, and assigns that patient to the group that will best serve the goal of balancing group size and, as study may require, key variables. Factors that might be considered include gender, age, stage of disease, or certain aspects of an individual’s past medical history. Dynamic randomization is sometimes referred to as a ‘minimization’ algorithm because it minimizes the imbalances in patient assignments. ICH has accepted the use of these dynamic techniques as a valid approach to randomizing subjects for drug trials.

Veracity Logic’s dynamic randomization algorithm is available as one of several randomization tools that are part of our standard CORE platform. When applied to a project, dynamic treatment assignment is tested as part of the standard project startup validation process. Three sample randomizations (with 150 subjects in each sample) are produced and provided to the client’s biostatisticians for review and approval prior to releasing the system for customer testing.

Predictive Inventory – Optimizing Drug Supply

Case Studies

The Challenge:

One of the greatest challenges in the conduct of a clinical trial is managing the expensive and often limited supply of investigational drug needed for the project. Anything that can help reduce waste and shipping costs while ensuring that clinical sites will have the drug they need when they need it is on the ‘most wanted’ list for the pharmaceutical industry. Since Interactive Response Technology (IRT) is one of the primary tools for drug assignment during a trial, the challenge has to be confronted by IRT vendors. How can control be achieved and maintained?

The Solution:

Veracity Logic’s Predictive Resupply algorithm is one of the tools for achieving efficient waste reduction while retaining an adequate drug supply where drug is needed. The algorithm takes into account a myriad of variables that impact on drug needs and timing. For example, the expected early withdrawal rate anticipated for a study can impact on the quantity of backlog maintained at a site for patient visits. Likewise, a study’s projected screen fail rate may determine the quantity of supply shipped to sites prior to randomization. The optimal number of inventory days at a site, the frequency of shipments desired by the sponsor, and shipping duration are also key impact variables that contribute to intelligent drug control.

Veracity Logic adds two more critical features to its proprietary predictive algorithm — the ability to control all key variables at the individual site level, and the ability to easily modify, on a configuration basis, the values assigned to each key variable throughout the clinical trial. In other words, we make Predictive Resupply sufficiently flexible to meet the changing, real-life needs of a study in progress.

Direct-to-Subject Shipping

Case Studies

The Challenge:

In order to help meet global enrollment targets, the Sponsor wanted to reduce the number of clinic visits each subject would need to make while still being able to assign drug every week. The goal was to find a way to deliver drug directly to subjects at home, and on a discretionary basis. Additionally, the Sponsor wanted to allow sites/subjects to be able to choose (and change their minds if need be) at a visit level whether to receive drug at home or by visiting the clinical site.

The Veracity Logic Solution:

A Direct-From-Depot option was added to the IRT system for all visits at which direct-to-home shipping would be allowed. At the Site level, the list of Resupply options in which the Site could participate was expanded to include the Direct-to-Subject option. At the Kit level, the system defined whether a particular kit type could be sent direct to Subjects (e.g., run-in kits were excluded from direct-to-subject). When all three key variables – Subject Activity, Site Resupply, and Kits – were in agreement, Direct-to-Subject shipping was enabled. The Subject visit was recorded, and an Activity Notification was sent to the warehouse with a request that the assigned kits be shipped to the subject’s address (on file at the warehouse).

Shipment options could be modified by each clinical site as needed throughout the study by means of a simple configuration change. By these methods, sites were able to easily adjust to the subject’s preferences while boosting enrollment and compliance.

Let Veracity Logic help with your study challenges!

Using Veracity Logic IRT’s Help Page…

Case Studies

Help, how do I get new documentation to the users?!
Problem:

Mid-study issues make it clear to your Project Manager that sites need new instructions to improve and clarify certain aspects of study conduct. The Project Manager puts together a User Guide, in six languages, for all study sites. The question now is how best to provide it to the clinical sites to insure it will be readily available for easy use.
Solution:

Veracity Logic’s IRT solves this problem by allowing authorized users to upload on-screen User Documentation as a standard feature of the system. The control is in your hands … users can easily add documents to the system via a simple ‘Upload Document’ button on the Help page off the Main Menu. Documents uploaded can relate to any aspect of your clinical trial –not just user manuals but process updates, new guidelines, even simply to disseminate interesting news. Outdated material is easily removed or replaced, making it easy to keep information current as things change throughout the study.

Want to know more about the standard offerings of Veracity Logic’s IRT?

Accessing Event Notifications

Case Studies

The Challenge:

For a study lasting several years, it’s common to have turnover of study personnel. When this happens, new users need access to the notifications sent by the system prior to their arrival. Typically, new users have to ask for printouts of specific prior notifications, or the Help Desk is asked to send copies of all the past notifications generated for the site. How to streamline the process?

The Solution:

The Veracity Logic development team revised the Messages functionality of the IRT CORE system so that new users are, by default, able to view ALL of the notifications generated since the beginning of the project and appropriate to their assigned user role and site(s). Users can also choose to re-send prior notifications on demand.

Requesting Shipments …

Case Studies

Shipments, manual or automated, have it your way…
Problem:

So it’s time to decide what types of shipment requests you’ll use in your clinical trial. There will be crunch times when Manual Requests are essential; other times when system-generated Automatic Requests are optimal (i.e., generating a shipment when a site’s inventory reaches a pre-set level). For some studies, a Predictive approach (modifying resupply based on multiple variables) is desirable to prevent drug wastage and to keep busy sites from running out. And if these decisions weren’t hard enough, sites for which you wish to use the Predictive model vary in key components of the resupply algorithm, for example, the number of days it takes a shipment to arrive from the warehouse. What to do?
Solution:

Veracity Logic’s IRT is designed to provide maximum flexibility in the options available for shipping study drug.

Just as no two patients are alike, so are no two sites alike—therefore the VLIRT® system allows variation at the site level. For example, sites can vary in:

Whether or not Manual Requests are used
Whether or not Automatic resupply is used
Whether or not Predictive resupply is used
Alert levels for Automatic resupply
The values of predictive variables used to calculate resupply on a ‘need’ basis
The amount of resupply applied to Predictive models

VLIRT® also makes it easy to modify a site’s shipping preferences during the trial. And even sites receiving automatic shipments are given the additional ability to generate manual requests on demand whenever the need arises.

Want more details?

Handling Data Corrections…

Case Studies

Problem:

There are many options for processing manual data changes in an IRT system. Some vendors make all data changes for the clinical site users. Others have electronic systems where users can request and approve changes, while still others require ‘wet’ signatures. What’s the best option for achieving the two key goals of change control, i.e., documenting user approval while streamlining the process so it doesn’t take days to make a change?
Solution:

At Veracity Logic, we put our emphasis on enabling and training authorized end-users to handle most manual data corrections themselves, just as they do in their EDC systems. The range of edit permissions varies based on the needs of each project.

We’ve found that most users not only don’t mind having the power to make many of the data corrections within the IRT, they actually prefer it to having to generate paper requests and factor in vendor response time (not to mention the increased cost of PM and Help Desk involvement).

For changes that technologically require vendor action, we make the change for them using a documented paper/signature trail. We don’t require the document contain a ‘wet’ signature, a faxed or PDF’d copy is sufficient.

Regardless of the method used, a proper audit trail must be kept whenever changes are made to clinical data by authorized users and it needs to include a justification/reason for the change. That said, when such capabilities (proper authorization, a full audit trail and requirement for recording the reason for a data change) are included in an IRT system, tied with the ability to ‘attach’ notes to records within the database, the additional time/effort of a laborious paper-based process is unnecessary.

Tracking Temperature Deviations…

Case Studies

Yikes, someone left the package out in the heat!
Problem:

Your drug must remain within a set temperature range at all times. How are you going to ensure drug that experiences a temperature deviation is not distributed to subjects?

Your packaging and transport vendor(s) will record temperature deviations that occur between the manufacturer and the clinical site. Great! But what about the IRT’s inventory tracking? How does it know to hold that drug? And what to do with it next?
Solution:

When the site receives the shipment, they will have to answer the question, “Did the shipment experience a temperature excursion?” before being able to proceed. If yes, Veracity Logic’s IRT gives you the power to make important decisions:

You can specify which types of temperature excursions occurred – i.e., ambient, refrigerated, frozen, or all three.
You can specify whether some or all of the kits in the shipment were affected.
After reviewing the temperature excursion details, you can decide to reinstate a kit or a shipment and make it once again ‘available’ for assignment to subjects.
Conversely, you can quarantine the kit or shipment after reviewing the deviation details. Quarantined kits will remain unavailable for assignment and will automatically be replaced in inventory in the next shipment.
You can designate kits and shipments for destruction or for return to the warehouse.

In other words, Veracity Logic’s IRT gives you the flexibility to meet real-life scenarios with real-life solutions.

Drug Hiatus…

Case Studies

Hey, I need a break from the dosing regimen…!
Problem:

Your study has a fairly complex drug titration pattern. In addition to multiple pre-planned titrations, subjects in your clinical trial can go up or down one dose level in the maintenance phase, based on medical assessment. If the subject has an unusual medical event intervene in the ‘dose escalation’ phase – for example, a hospital stay for an unrelated issue – the subject may either need to be discontinued from the trial or somehow be permitted a ‘drug vacation’ after which the system will permit return to a previous dose/visit level or movement to a new level. How to do this with an IRT?
Solution:

Other IRT systems may not allow this flexibility. But Veracity Logic’s IRT includes a ‘drug hiatus’ functionality which permits a subject to maintain their regular visit schedule but take a break from drug assignment. At the end of the hiatus period, its length set by protocol or flexibly determined by medical assessment, subjects return to drug assignment, either at the previous dose level or at a new level.