Penn Medicine Clinical Research

Protocol Design

A protocol design or research proposal is a written plan of the research. The protocol design can have any format or template. As long as the protocol design contains the necessary information the protocol is good. 

 Elements of a Study Design: 

 In all types of research, a clear hypothesis is necessary in order to choose the study design. Once the purpose of the investigation is understood and the hypothesis and objectives have been formulated, it is necessary to identify the study design to be used for the project in order to rigorously rest the hypothesis.   

  • Experimental/ Interventional Study Design- typically randomized clinical trial   

  • Control Groups  

  • Random Assignment  

  • Blinding and Placebo Control (singe blind, double blind, triple)   

  • Observational Study Design  

  • Population health   

  • Cohort Studies   

  • Case Control   

  • Cross sectional   

Frequently Asked Questions

A: A protocol is a document that describes the objectives, design, methodology, statistical considerations, and organization of a research study. The protocol is distinct from the research grant in that a research grant is a broad overview of the study procedures, while the protocol clearly defines and operationalizes the details of study implementation. The required elements of a study protocol are dictated in the Good Clinical Practice (GCP) standards. The protocol includes detailed procedures, methods and calculations to ensure the safety of research subjects and the quality of the research data. The OCR website has protocol templates which can be used as a starting point.    

A: There are four different phases of a clinical trial  

  • Phase I - first study of a drug in humans, most commonly healthy adults although it might also include patients with no other clear treatment options for example in oncology research; safety and dose ranging tolerability; basic metabolism or mechanism studies (generally small studies of 20 or fewer subjects).  

  • Phase II - first study of drug in target populations (patients); safety, dose ranging in patients; preliminary efficacy assessment (generally 100-300 subjects)  

  • Phase III - larger study to prove efficacy and increase experience with safety (generally large studies ranging from 100 to >1000 subjects   

  • Phase IV - post-marketing studies; vary in size; often to provide ongoing safety data.  

A: Most often the assistance of a statistician will be required for the selection of an experimental design, the development of the corresponding analysis plan and the subsequent interpretation of parameter estimates and test results.  The importance of early involvement of a statistician in the design of a clinical study cannot be overstated.  

A: Penn has many offices that can support your statistical needs. The Center for Human Phenomic Science (CHPS) has the Study Design and Biostatistical Core (SDAB). The Center for Clinical Epidemiology and Biostatistics has The Department of Epidemiology and Biostatistics (DBEI), and the Biostatistics Analysis Center (BAC). The Children’s Hospital of Pennsylvania (CHOP) has the Biostatistics and Data Management Core (BDMC).  

A: An amendment or modification is a change to the research protocol that may be initiated by various sources, however, the final decision to approve and release a protocol amendment rests with the (regulatory) sponsor.  Protocol amendments may be administrative changes, clarifications, modifications, and changes to the study design. Amendments to the protocol may also require changes to other core study documents such as the ICF, CRFs, or study manuals.  Protocol amendments may take place before a study goes to IRB for approval but may also occur once a protocol is already IRB approved and then need to be submitted for approval before initiating. Protocol amendments will come from the Sponsor of the trial and the site will submit it to the IRB for approval.   The Sponsor is responsible for notifying or obtaining FDA and/or key collaborators of protocol amendments prior to implementation.