PRE-AWARD PAPERWORK FOR CLINICAL TRIALS

SERIES 4 , SESSION 8OCTOBER 28 , 2014

Applicants and Administrators Pre-Award

Luncheon Series

Presented By:

Kathleen Benoit – Research Administrator, OFFICE OF RESEARCH ADMINISTRATION, BOSTON

Overview

What is a Clinical Trial?

Clinical Trial Phases

Preparing the Proposal

• Payment Terms and Budgeting

What is a Clinical Trial?

A study on human subjects to answer questions about biomedical or behavioral interventions novel vaccines drugs treatments functional foods dietary supplements devices or new ways of using known interventions

Clinical Trial Phases

Phase I – dose finding toxicity

Phase II – efficacy & safety

Phase III – compare to standard treatment

Phase IV – post marketing after FDA approval

Breakdown of the Phases

Phase I – Testing in a small group of people (roughly 50 subjects) to determine efficacy and evaluate safety e.g. determine a safe dosage range and identify side

effects

Phase II – Study in a larger group of people (roughly 100 subjects) to determine efficacy and further evaluate safety

Breakdown of the Phases, cont.

Phase III – Study to: determine efficacy in large groups of people (from

several hundred to several thousand) by comparing the intervention to other standard or experimental interventions

monitor adverse effects; and collect information to allow safe use

includes pharmacologic, non-pharmacologic, and behavioral interventions given for disease prevention, prophylaxis, diagnosis, or therapy; and community trials and other population-based intervention trials

Breakdown of the Phases, cont.

Phase IV – Studies done after the intervention has been marketed. Designed to: monitor the effectiveness of the approved intervention

in the general population collect information about any adverse effects

associated with widespread use

One phase must be completed before the next phase can begin

The Phases - Overview

Phase I Phase II Phase III Phase IV

Purpose Dose finding toxicity

Efficacy & safety

Compare to standard treatment

Post marketing after FDA approval

Number of Participants

< 50 < 100 100 into the thousands

Any number

Location Phase I Center or University

University, Large Medical Center or Private Office

University, Large Medical Center or Private Office

Private Office or Medical Center

Goal Determine safe dose & possible indications

Efficacy in specific clinical situations

Evaluate in comparison to standard or no treatment

New indications or long term impact on quality of life

Common Study Design

Dose escalating cohorts

One arm, may be stratified

Randomized, blinded, multi-arm may be placebo controlled

Open labeled; expanded access

The Protocol

How a clinical trial will be conducted (objectives, design, methodology, statistical considerations and organization)

Number of study subjects depends on the required sample size

Criteria for selection and exclusion of subjects, assessment of efficacy and safety, study monitoring plan, and quality control & assurance

Ethics and handling of adverse eventsData handling and recordkeepingPublication plan, literature reference, timetablePI is responsible for the welfare of the study subjects,

study data, compliance with regulations

Developing a Budget

Budget needs to be somewhat flexible and must cover all costs

Fixed and upfront costs are incurred whether or not subjects are enrolled

Costs related to subject visits depend on the number of participants

Analyze the study timeline to identify items that will generate expenses for the site

Create detailed budget by visit and by study cycle

Budget Items

Required professional charges for the tests being performed Inclusion of one-time charges

IRB Investigational drug (IND) pharmacy start-up fee

Human subjects charges Advertisement/Recruitment Stipends Travel Meals Parking

Laboratory assessments and pharmacy fees Don’t forget F&A (use ‘other on-campus rate of 37%)

Cost-Related Considerations

Realistic number of subjects that can be recruited

Number of subjects that need to be screened to identify an eligible participant

Difficulty of meeting eligibility criteria and additional recruitment effort

Delayed start will increase costs

Subject Screening and Costs

Most allow for up front fees (inclusive of one time charges) to be paid in full before the study begins

When determining per patient costs, be mindful of: Initial screening Failure after screen and/or during the life of the study Drop-out rates Full completion Does the sponsor require a final amount of patients

(i.e. must see 100 patients for successful completion)? Is this number flexible?

Tracking Costs

Ensure that all costs are tracked accurately for invoicing

Sponsored Programs Accounting relies on the accuracy of the information provided by the Project Coordinator and Administrator

Understand all terms from the Sponsor before beginning Are the study and fees feasible for the institution?

Clinical Trials Registration

All clinical trials must be registered in the US Clinical Trials database: https://clinicaltrials.gov/ provides patients, their family members, health care

professionals, researchers, and the public with easy access to information on publicly and privately supported clinical studies

maintained by the National Library of Medicine (NLM)

Information is provided and updated by the sponsor or PI

Studies are submitted to the website (that is, registered) when they begin, and information is updated throughout the study in some cases, results are submitted after the study ends

Clinicaltrials.gov

Request registration from your Signing Official (SO)at ORA to receive access

Once information is entered or updated, the SO will have to release the information

Clinicaltrials.gov staff maintain quality control and may reject incomplete information or request edits before posting

Information must be updated in a timely fashion

Record must be closed once the trial is completed

Take-Aways

Work closely with the sponsor to design the study

Be realistic about subject recruitment Analyze the timetable to create

adequate budgetMonitor costs closely to avoid problemsClinical trials registration is mandatory

Questions ???

Questions?

Please feel free to call Kathleen Benoit at 617-636-0414or email kathleen.benoit@tufts.edu