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