Development Process: Plan with the End in Mind

Protocols

Protocol Outlines

Clinical Development Plan

Non-Clinical Plan

Commercialization

NDA (BLA)/MAA Submission(s)

Registration Strategy

Integrated Summaries

Final Reports

Study Conduct

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Drug Development Regulatory Provisions

§  Fast Track Development Status - To expedite product development

§  Orphan Drug Status - To encourage development of drugs for rare diseases §  Accelerated Approval

- To speed approval in a life-threatening disease based on surrogate marker data with a commitment to conduct confirmatory studies §  Key Consideration - Benefit risk assessment

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Drug Development Imperative: Prepara&on  of  Target  Product  Profile  

§  Considerations –  Indications –  Target patient populations –  Efficacy profile –  Safety profile –  Formulations –  Dosage regimens

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Input Into Drug Development Program

§  Involve Constituencies  

-­‐  Regulatory Agencies

-­‐  Key Investigators & Opinion Leaders (KOLs) -­‐  Patient Advocacy Groups

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Clinical Trial Statistical Considerations Two Separate Assessments

Pre-­‐Study  Sample  Size  Determina3on  

(Output:    number  of  pa3ents)  

Assump&ons  

§  Power (80%)                          -­‐                  Probability of sufficient number of

patients studied to detect a difference (avoid false negative)

§           α  value  (≤0.05)  

                       -­‐                  Probability of result occurring by chance (avoid false positive)

§         Difference  to  be  detected  

§  Enrollment  period  

§  Follow-­‐up  dura3on  

[Prespecified  Sta&s&cal  Analysis  Plan]  

 

             Post-­‐Study  Sta3s3cal  Analysis  

                       (Output:    p  value  result)    

Assessments  

§  Primary  endpoint  (eg,  pa3ent  survival)  

§  Sta3s3cal  test  to  determine  p  value  (eg,  modified  log-­‐rank  test  to  compare  Kaplan-­‐Meier  pa3ent  survival  curves)  

[Post  Hoc  Sensi&vity  Analyses]  

 

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Regulatory Meeting Preparation

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 § Back  to  Basics  

• WHO  • WHAT  • WHERE  • WHY  • HOW  

 

Regulatory Preparation: Back to Basics

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 § WHO      

• Iden6fy  individuals  from  the  Regulatory  Agencies  who  will  be  involved  in  interac6ons  so  the  right  company  and  external  experts  are  available  for  mee6ngs  and/or  teleconferences  

 • Contact  external  experts  as  soon  as  possible  to  ensure  their  availability  

 

   

(is going to be involved)

Regulatory Preparation: Back to Basics

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 § WHAT    

• Compile  a  complete  list  of  ac6vi6es  that  need  to  be      accomplished  for  the  mee6ng  

 • Do  not  overlook  details  which  can  cause  delays  or  inconvenience  such  as  booking  a  sufficient  number  of  hotel  rooms  

 

(needs to be done)

Regulatory Preparation: Back to Basics

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 § WHERE    

• Determine  loca6on  of  mee6ngs  early  on  to  facilitate    travel  and  hotel  bookings  

 • Prepare  for  con6ngencies  such  as  the  possibility  of  extra      aRendees  

 

   

(will prep meetings and actual meeting be held)

Regulatory Preparation: Back to Basics

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 § WHY  (the  need  for  a  mee6ng  should  be  asked                      to  provide  clarity  of  mee6ng  goals  and  details  to                      facilitate  prepara6on)  

                     • Establish  rapport  as  possible  with  Regulatory  Agency  staff  to  assist  with  planning  

 • Hold  prep  teleconferences  and/or  mee6ngs  to  minimize  disconnects  

   

Regulatory Preparation: Back to Basics

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 § HOW                                      • Prepare  a  6me  and  event  schedule  to  delineate      expecta6ons  

 

   

(will logistics be coordinated to avoid duplication of activities)

Regulatory Preparation

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 §   Needs    

• Iden6fy  the  goals  for  the  mee6ng    • Understand  how  work  is  distributed    • Foster  collabora6on      

Regulatory Preparation

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 §   Details    

• Know  the  audience  -­‐    Obtain  informa6on  on  their  exper6se    

• Try  to  preempt  an6cipated  ques6ons  in  the  briefing  document  -­‐    Understand  Agency  stance  on  topic(s)  to  be  discussed  

 

Drug Development

§ Critical Success Factor −  Upfront  planning  to  prevent  problems  

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Drug Development

Quality

Time Cost

Drug Development

Align Goals and Incentives for Success

Key Factors in Drug Development - Balance

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