How to Set Up and Begin Clinical Research Jeffrey M. Burns, MD Associate Professor, Department of Neurology Director, KU Alzheimer and Memory Program Assistant Director, General Clinical Research Center

Challenges in Clinical Research Expensive Study people – Difficulty controlling the exposure: type and timing – Clinical measures Recruitment

Clinical Trials vs. Investigator-Initiated Clinical Trials – Regulatory hurdles – Recruitment Investigator-initiated – Protocol development – Data management / analysis – Funding

Initiating a Clinical Trial Regulatory – HSC Consent form – Contracts and budget Research Institute Recruitment plan – Clinic – Coordinator

Recruitment of Subjects Do not overlook this process (Your reviewers will not) Often the most difficult aspect to successfully implementing your plan (weakest link) Recruitment coordinator Detailed and well-thought out plan

Recruitment Plan Clinic recruitment – Database created Brochures Media – Radio shows (Walt Bodine, Steve Kraske) – TV and Newspaper – Press Release Alzheimer's Association Physician Referral Advertising – Radio – Newspaper – Website Google keyword advertising

Phone Inquiry Form Data entered into a log for future recruitment opportunities

Investigator-Initiated Clinical Research Limiting Factors – Money – Participants Major Challenges – Protocol development – Data management plan

The Right Question Feasible The right balance of you and your environment’s strengths AND limitations – Important considerations: Your experience / preliminary data Your environment: utilize strengths  expertise and equipment – FINER Feasibility, Innovation, Novelty, Ethical, Relevant

The Aims Page Your roadmap One-page summary of the entire study – Paragraph 1: rationale and overall hypothesis – Aims – 3 to 5 main questions Evolving document – Write and rewrite based on the process of building your research project and input from others.

Protocol The evolution of a protocol from its initial version to the final document creates a systematic approach to the development of a clinical trial that is acceptable on ethical, scientific, and organizational grounds. The final version of a protocol should serve two primary functions: Provide detailed specifications of the trial procedure relating to each individual patient Describe the trial’s motivational background, specific aims and rationale for the design Slide courtesy of Holly Smith

Protocol Main Protocol Features 1. Background and general aims 2. Specific objectives 3. Patient selection criteria 4. Treatment schedules 5. Methods of patient evaluation 6. Trial design 7. Registration and randomization of patients 8. Patient consent 9. Required size of study 10. Monitoring of trial progress 11. Forms and data handling 12. Protocol deviations 13. Plans for statistical analysis 14. Administrative responsibilities Slide courtesy of Holly Smith

Measures / Outcomes Details, details, details Standardized Valid and Reproducible Relationship of fitness with AD progression How to measure AD progression? Measuring fitness?

Data Management How will you collect the data? – Paper, direct data entry – What will be entered into a database and how? Source documents Case report forms Data entry plan, database structure Mistakes are inevitable Must make all forms and records as fool-proof as possible

Source Documents Used to collect information during the patient encounter or performance of the study.

Case Report Form Used to extract most important data from source documents for data entry / analysis.