The 3 Ps: Submitting an Amendment vs. a New Study

February 2026 Issue

Author(s):

• Jamie Merrill, MPH, CIP, Director, BMC/BUMC IRB

PRINT

• Introduction
• The 3 Ps Framework
• Working Through Each P
• When It's Always a New Study
• Special Situations
• Decision Flowchart
• If You're Submitting an Amendment: Tips for Success
• Common Scenarios
• Summary

Introduction

"Should I submit this as an amendment or a new study?" This is one of the most common questions the IRB receives from investigators. As research evolves, new funding arrives, collaborations develop, and scientific directions shift, study teams frequently need to determine whether proposed changes belong in an existing protocol or warrant a fresh submission.

It is a common misconception that submitting an amendment to an existing study will always be easier and faster than submitting a new Initial application. In reality, the IRB must examine any amendment using the same review criteria and standards as a new submission. An amendment that results in an overly long application with many inconsistencies and/or the inclusion of information that is no longer relevant can be confusing to reviewers and can negatively impact overall review efficiency. In many cases, a new protocol that is current and consistent will actually be easier to review and faster to approve.

This Feature Article introduces the "3 Ps" framework: a practical tool, originally developed by Harvard IRB, for making this determination. We will walk through each component, discuss categorical rules and special situations, and provide scenarios to help you apply this framework to your own research.

The 3 Ps Framework

When the IRB assists researchers in determining whether proposed changes should be incorporated into an existing project or submitted as a stand-alone project, we consider the 3 Ps: Purpose, Population, and Procedures. That is, we consider whether the proposed changes:

• Are meant to answer the same research aims as the current protocol (Purpose)
• Are generally focused on the same population of interest—not necessarily the same sample, but with unifying qualities (Population)
• Are complementary to the already approved procedures (Procedures)

If all 3 Ps align, an amendment is likely appropriate. If they diverge, particularly if more than one P is affected, a new Initial submission is likely needed.

The IRB will most heavily weigh how well-aligned the existing study and proposed changes are in their research goals. If adding new directions in your procedures appear to reflect new goals for your research, the IRB will likely advise a new application.

Working Through Each P

Purpose: Do the proposed changes alter the research hypothesis or aims?

The research purpose is the foundation of the 3 Ps framework. If your basic research question remains intact, a new application may not be needed. However, if the focus or research question has changed, even if it builds on knowledge learned in the existing study, a new application may be warranted.

Why does this matter so much? The IRB must assess the risks and benefits of research and balance the risks against the benefits. If the research question has changed, then the benefits have likely changed as well. A new application allows the IRB to properly evaluate whether the new risk-benefit balance remains favorable.

Likely an Amendment: "We want to add a follow-up survey at 12 months to assess longer-term outcomes for our intervention study."

Likely a New Study: "Our depression treatment study has revealed interesting findings about sleep patterns. We want to studying sleep interventions in this population."

Population: Are you studying the same group of people?

Consider whether the proposed changes involve the same general population of interest. Minor adjustments to inclusion/exclusion criteria that don't fundamentally change who you're studying will typically support an amendment. However, targeting a substantially different population, especially one with different vulnerabilities or risk profiles, often warrants a new submission.

Likely an Amendment: "We want to expand our age range from adults 21-40 to adults 21-60."

Likely a New Study: "Our adult hypertension study has been successful. We now want to study adolescents with hypertension using similar methods."

Adding vulnerable populations (children, pregnant people, prisoners, individuals with diminished decision-making capacity) to a study that didn't originally include them requires careful consideration. The additional protections required and the distinct risk-benefit analysis for these groups will often necessitate a new application.

Procedures: Are the new activities complementary to existing ones?

Consider whether the procedures and methods remain essentially the same. If you're substituting one questionnaire for a similar one or adding a procedure that fits naturally within your existing study design, an amendment is likely appropriate.

If the new procedures deviate substantially from those proposed in the original research plan, then a new application may be warranted. This is especially true if the changes create what can be called a "menu" of procedures—where multiple combinations of activities might be used with different participants, making it difficult for the IRB to assess risks to individual participants.

Likely an Amendment: "We want to replace the PHQ-9 with the PHQ-8 for our depression screening."

Likely a New Study: "Our observational survey study has identified a promising intervention. We want to add a randomized treatment arm."

The "Unwieldy Study" Problem

Unwieldy studies are a challenge for both the IRB and research teams. From the researcher perspective, studies that morph over time through multiple amendments can become unwieldy with multiple add-ons, blur the focus of the research, and affect data quality. This can cause confusion and errors among research team members, leading to non-compliance with the approved protocol and potentially impacting risks to participants.

From the IRB perspective, if changes result in a "menu" of procedures, then it becomes difficult to assess the risks of the research to individual participants. Reviewers would need to consider all possible combinations of materials and procedures for all possible participants. In these cases, a new application is often the better course, as an amendment could lead to multiple rounds of revisions. The IRB strongly prefers that investigators complete their approved study and open a new one, rather than trying to heavily amend a previously-approved study.

When It's Always a New Study

Certain situations categorically require a new study submission, regardless of how the 3 Ps might otherwise align:

• Adding FDA-regulated products: Adding investigational drugs, devices, or biologics that are FDA-regulated to a study that was not previously FDA-regulated requires a new study. The IRB will need to make new regulatory determinations, and the study may now be subject to FDA regulations.

• Secondary use of repository/registry data: Requests to use data or samples from repository and registry studies to conduct new analyses require a new study submission.

• Different lead investigator: If the newly introduced procedures will be led by a different Principal Investigator, then a new IRB application should typically be created to ensure clear accountability.

• Changes affect more than one P: When proposed changes modify two or more of the 3 Ps (for example, new aims AND a new population), then a new study is typically required. Keep in mind that submitting multiple amendments over time that collectively change more than one P should also prompt consideration of a new study.

Special Situations

New Funding

If new funding is awarded to support the research as currently approved, then an amendment to associate the funding is appropriate. However, if new funding points to new directions for the research and the aims or research design need to change, then a new application can cleanly delineate this new focus and ensure the approved protocol is accurate and relevant to the planned research.

Example: A study is federally funded, and an investigator obtains an NIH supplement to add a specific element to that study. The original funding is still necessary to complete the study; and although the supplement adds a new procedure, the study population and overall design remain the same. This would likely be appropriate as an amendment.

Long-Running Studies

If the protocol is intended as a longitudinal study or is operating within the planned study timeline, and if changes are otherwise closely related to the previously-approved study, then an amendment is likely appropriate.

However, if the protocol has been active for several years and was not intended for longitudinal research, then the information within the protocol can become inaccurate as institutional policies, clinical standards of care, and research personnel change. Protocols open for an extended period may include irrelevant information as portions of the research may be complete, creating confusion about what activities are ongoing. As new risk information becomes available, long-running studies may not reflect the most current information.

A new application allows the protocol to be refined to meet current research objectives, incorporate current standards of care and risk information, and ensures the study remains compliant with the most up-to-date policies and guidelines.

Cumulative Drift

Even if each previously-approved amendment was appropriate, multiple amendments over time can collectively transform a study. If your study has been amended numerous times and now looks substantially different from the original submission, then consider whether a fresh start would provide clearer documentation and easier compliance going forward.

Decision Flowchart

See the accompanying flowchart for a visual guide to this decision process. The flowchart walks through:

• Stage of research (early stage vs. mid/late stage)
• Categorical rules that always require a new study
• Assessment of each of the 3 Ps
• Contextual factors (study duration, cumulative drift, new funding)

Amendment vs. New Study Decision Flowchart
Adapted from Harvard IRB and NTU Singapore IRB

STEP 1: What stage is your research?

STEP 2: Do any categorical rules apply?
If ANY of the following apply, submit a New Application:

If none apply → Continue to Step 3

STEP 3: Assess the 3 Ps

↓ If YES to all three

STEP 4: Consider contextual factors

↓ If no contextual concerns

If You're Submitting an Amendment: Tips for Success

If you've determined that an amendment is the right path, here are common reasons amendments fail to obtain approval during initial review, and how to avoid them:

• Explain the rationale: Don't just describe what is changing—explain why the change is necessary.
• Implement changes consistently: Ensure the proposed change is reflected throughout all relevant documents: the protocol, IRB application, consent form, recruitment materials, etc.
• Update your analysis plan: If changes affect your objectives, endpoints, measurements, or sample size, then update your analysis plan accordingly.
• Submit the right documents: Verify you're submitting the correct versions of all affected documents.
• Upload clean WORD documents, if possible: Ensure that there are no track-changes or comments in the document – submit the final version you intend to use. INSPIR struggles with PDFs and other file formats.
• Document all changes: Every change in study documents should be described in your Change Request. Reviewers should not encounter undiscussed changes when reviewing your materials.

Common Scenarios

The following scenarios illustrate how to apply the 3 Ps framework. Blue boxes indicate a New Study is needed; green boxes indicate an Amendment is appropriate.

Summary

The 3 Ps—Purpose, Population, and Procedures—serve as a helpful framework when deciding whether an Initial submission or an Amendment should be submitted:

Remember: The IRB reserves final authority in determining whether changes can be submitted via an amendment or if a new study application is required. The 3 Ps framework is guidance and NOT an exhaustive checklist. Check in with the IRB team before submitting if you're ever in doubt!

You can reach the IRB at medirb@bu.edu.