Infosheet aces-what-is-aces-and-where-is-it-being-used
Transcript of Infosheet aces-what-is-aces-and-where-is-it-being-used
What is ACES® and Where it’s Being Used
For both tradi+onal and adap+ve trials, ACES addresses the secure communica+on complexi+es and regulatory concerns with interim analysis.
Since introduced in 2010, we’ve deployed the web-‐based system in Phase 2 and Phase 3 adap+ve and tradi+onal trials across a variety of therapeu+c areas including oncology, CNS, infec+ous diseases, immunology, and psychiatry/psychology.
Access Control Execu/on System
Independent expert commiJees – Data Monitoring and Endpoint Adjudica+on – while increasingly important, add administra+ve complexity for clinical trial sponsors. Securely managing the exchange of confiden+al informa+on for these commiJees also exposes sponsors to the great risk of compromising the integrity of their study.
Why Sponsors are Implementing ACES Key Benefits
1. Regulatory Trust and Confidence ACES® is foremost designed to achieve regulatory trust. It conforms with the FDA Guidance and EMA posi+on on DMCs and Adap+ve Trial Design providing evidence that a trial is conducted with a secure process, including a ‘who saw what and when’ audit trail. 2. Streamlined Workflow ACES is purpose-‐built to comprehensively manage clinical trials and interim analyses, including the documenta+on and firewalls necessary to preserve trial integrity.
ACES automates many tasks – like DMC no+fica+ons, reports, or randomiza+on and treatment updates for IWRS and drug supply. It’s web-‐based and easily deployed in any seXng. 3. Decision Engine Integra/on It’s what sets ACES apart from ordinary document management packages like Documentum and SharePoint-‐based apps. ACES ability to integrate these engines is helping sponsors of all sizes make even their most complex trials more rou+ne.
Typical Decision Engines can involve dose selec+on, randomiza+on schemes, drug supply triggers, early stopping rules, adap+ve design simula+ons, and condi+onal power calcula+ons. The results are reported as specified in the protocol, and only to those permiJed.
Case Study - ACES Deployed in a Seamless Phase 2 / 3 Adaptive Trial
The Trial Design and ACES Ini+ally, randomize subjects equally across four treatment arms, then perform interim analysis once enrollment reaches about 100 subjects in each arm.
The trial’s interim analysis decision rules: 1. Early termina+on for fu+lity 2. Dose selec+on: select one or two most
ac+ve doses (observed paJerns of response rates) with placebo to move into trial’s 2nd stage
3. Sample size increase: a one-‐+me increase based on condi+onal power for 2nd stage
The dose selec+on rules were also loaded into ACES, together with the randomiza+on table and treatment codes.
Secure Reports and Communications Between Sponsor – DMC – ISC – Site
ACES Supports DMC The trial’s DMC reviewed the analysis report, suppor+ng tables, lis+ngs, and graphs, provided with ACES and made their recommenda+on to the sponsor.
ACES securely stored the recommenda+on and triggered no+fica+on to the sponsor company representa+ves to review and accept.
The pivotal VALOR trial valortrial.com is an example of ACES use to support a sample-‐size re-‐es+ma+on confirmatory study in oncology.
ACES Use Documented at ASCO Protecting the Integrity of Adaptive Designs
(Per the) Guidance documents by FDA and EMA for DSMB and Adap>ve Trial Design, sugges>ng ‘A well-‐trusted firewall established for trial conduct ... can help provide assurance that sta>s>cal and opera>onal biases have not been introduced.’
Cytel’s Cyrus Mehta and Eric Silva with Sunesis Pharmaceu+cals co-‐authors From their accepted ASCO 2012 poster presenta+on