Pathway to Clinical Endpoint BE trial dosing

The following checklist provides a summary of the preparatory steps your group should perform in the months prior to dosing your trial’s first subject. The Appian team has streamlined many of these functions and will guide your group through the process to ensure that your study doses on-time.

             6 months ahead

1. Define the study objective and rationale.
2. Review literature and discuss with experts.
3. Decide on the study design.
4. Calculate sample sizes and prepare the statistical plan.
5. Plan rough timelines for the study course.
6. Prepare the project plan.
7. Check availability of study medication in principal terms.
8. Decide on test drug(s) and comparator drug(s).
9. Decide on detailed timelines for study preparation, performance, and evaluation, including critical time points.
10. Decide on the countries of interest.
11. Identify and decide on study management technologies.
    
    5 months ahead
12. Identify potential investigators.
13. Decide on countries involved, number of sites, and number of subjects per site.
14. Decide on final list of potential investigators.
15. Prepare a contingency plan for nonactive investigators.
16. Start preparation of the investigator brochure.
17. Order study medication.
18. Prepare a contingency plan for delayed availability of study medication.
19. Identify labeling and importation requirements for the study medication.
20. Decide on packaging and shipment strategy.
21. Prepare a contingency plan for packaging and shipping delays.
22. Find out about subject recruitment opportunities.
23. Plan the project team structure.
24. Identify project team members and their roles and responsibilities.
25. Prepare detailed resource plan for the overall study.
26. Decide on a resource contingency plan.
27. Implement study management technologies and train project team.
28. Find vendors for outsourced study activities and technologies.
29. Prepare vendors’ briefing documents.4 months ahead

1. Decide on vendors.
2. Finalize vendors’ budgets.
3. Plan and manage the audit of vendors.
4. Prepare and sign contracts for vendors.
5. Prepare, organize, review, and finalize communication plan with project team, vendors, and investigators.
6. Order packaging of study medication.
7. Decide on subject recruitment activities.
8. Prepare a contingency plan for slow recruitment.
9. Decide on the strategy for investigators’ meeting(s).
10. Identify, negotiate budget, and sign contract with the organizer of investigator meeting(s).
11. Decide on venue(s) and date(s) and prepare investigators’ meeting(s).
12. Prepare a template for investigator contracts.
13. Plan and organize prestudy visits.
14. Negotiate terms and conditions of contract with investigators.
15. Decide on final list of investigators.
16. Prepare study budget and seek approval.
17. Prepare a contingency plan for delays in budget negotiations and approval.
18. Prepare a study approval and ethics committee submission plan.
19. Prepare a contingency plan for ethics committee and study approval delays and/or problems.
20. Prepare draft protocol and plan and manage the review process.
21. Organize QA review of protocol.
22. Prepare final protocol.
23. Finalize contracts with investigators.
24. Prepare standard consent document.
25. Define and organize translation requirements for consent document.
26. Plan and manage review process for consent process in different countries.
27. Prepare standard consent documents per country.
28. Prepare advertisement plus other subject- and/or investigator-related information material.
29. Plan and manage review process for advertisement and additional information material in the different countries.
30. Finalize advertisement and additional information material.
31. Prepare, organize review, and finalize case report form (CRF).
32. Prepare, organize review, and finalize investigators’ brochure.
33. Organize translations of study material according to local requirements.
34. Plan the individual submissions to ethics committees.
35. Prepare, organize review, and finalize the ethics committee submission packages for all investigators.
36. Prepare, organize review, and finalize study approval submission package in countries with “parallel submission.”3 months ahead

1. Submit to ethics committees (and regulatory authorities in countries with “parallel submission”).
2. Prepare, manage review, and finalize audit plan.
3. Prepare drug labels.
4. Confirm site selection and budgetary-specific needs, including resources.
5. Collect all legally required information from investigators (that is, essential regulatory documents and contracts).
6. Collect information on national serious adverse event (SAE) and adverse event (AE) handling requirements.
7. Prepare, organize review, and finalize data management plan.2 months ahead

1. Submit regulatory study approval documents to respective authorities, if possible.
2. Plan and organize printing of the CRF (including enough “reserve”).
3. Prepare, manage review, and finalize the CRF convention manual.
4. Prepare, organize review, and finalize the monitoring convention manual.
5. Prepare training material for the project team.
6. Prepare, organize review, and finalize the SAE and AE handling plan.
7. Prepare, organize review, and finalize the safety database.
8. Verify roles and responsibilities for key processes, such as safety.
9. Prepare, organize review, and finalize database.
10. Finalize statistical plan.

    1 month ahead

1. Train the project team.
2. Hold investigators’ meeting(s).
3. Hold kickoff meeting with project team and vendors.
4. Ensure study approval and drug importation licenses.
5. Release study medication.
6. Manage study medication and material shipment to sites.
7. Plan and set up the investigator fees payment process.
8. Prepare site master files.
9. Organize study initiation visits, as required.
10. Ensure all study drugs and material arrived at sites.
11. Perform study initiation visits at sites with control of ethics and study approval, arrived medication, and other study material.
12. Train study coordinators and other involved site staff.
13. Initiate subject recruitment activities.

Adapted from I Klingmann, A Verny, A 6-Month Process for Planning Multinational Clinical Trials.  Applied Clinical Trials, 2003. Reprint available upon resquest.