• Protocol author
• Protocol reviewers
• Medical monitor
• Clinical scientist
• Statistician
• Regulatory
• Case report form (CRF) developer
• Data manager
• Clinical project manager
• Investigator
• Study coordinator

Consider the Stage of Development When Drafting Your Objective(s)

Considerations for a protocol in early stages of development are different than in later stages of development.  Keep in mind the overall objectives for your stage of development.  In phase I studies, remember your primary objective should address safety, with pharmacodynamics and efficacy as secondary objectives.  For phase 2 studies, efficacy is your primary concern followed by safety.   By phase 3, your primary objective should be about validation of efficacy with safety as a second primary concern.

Objectives for Early Phase Protocols

“The objective of this protocol is to determine the safety and efficacy of drug x in disease y” is far too vague.  A better objective sounds like “To evaluate the effects of a twice daily intravenous dose of medicine A in population B on the clinical endpoint C by recording measurement D at time period E relative to baseline versus a placebo.”  Note that the second objective contains these key elements:

• Product
• Patient population
• Generic dosing regimen (NOT dose)
• Clinical end point

You will also want to address:

• Safety analyses
• Efficacy analyses (if there are any)
• Phase

Objectives for Late Stage Protocols

For late stage studies, create your statistical analysis plan (SAP) before working on the other sections of the protocol.  By understanding the data you will need to analyze at the end of the study and the results you will want to show, you’ll know how many subjects you’ll need and what data you’ll need to collect about those subjects.  Then, you can use your SAP to simultaneously design your CRFs, set up your clinical database, and write the other sections of your protocol.

Additionally, determine Precedent Regulatory Clinical Endpoints for Late Phase Protocols intended to support efficacy requirements for registration.  To do this:

• Review recently approved precedent product package inserts
• Review ongoing clinicaltrials.gov protocols
• Ensure agreement with FDA for clinical endpoints through Special Protocol Assessment or End of Phase 2 meeting documentation

Draft a Protocol Synopsis

A five page protocol summary document that answers all the questions regarding the protocol design should be prepared as a first step in the preparation of any protocol.  A document containing all the critical headings of the protocol can be prepared and completed in abbreviated fashion striving to only write the text that is absolutely necessary.  Sections that are not critical to the development of the protocol (“boilerplate” e.g., Adverse Event Reporting) can be omitted unless there is something unusual about that protocol section in question.

Leave Logistical Details Out of the Protocol

Create a study procedures manual which contains the operational details of the study rather than including them in the protocol.  Operational details (e.g., laboratory sample preparation, personnel names, specific procedural details, etc.) are likely to change over the course of the study.  When they are included in the protocol, you will be forced to do a protocol amendment each time they change.  By keeping logistics that don’t impact the study design out of the protocol, you will save time and money by significantly reducing the number of protocol amendments.