CAPSTONE PROJECT
Human Subjects Research,
Regulatory Compliance
& IRB Practices
Dr. Meghana Karnaty
Clinical Research & Regulatory Affairs
Northeastern University MS-RGA
Mentor: Tasha Mohseni
RD Research Services, LLC
A Comprehensive Capstone Presentation covering the
Belmont Report, FDA Regulations, Clinical Pharmacist
Roles, IRB Practices, and Real-World Ethical Violation
Case Studies
Human Subjects Research
Pharmacy Compliance
FDA Warning Letters
Northeastern University Experiential Network
Presentation Overview
01
Capstone Project Overview
Goals, approach, and the 9-week capstone timeline at RD Research Services
02
The Belmont Report (1979)
Ethical foundation of human subjects research — three core principles
03
Regulatory Framework
The Common Rule (45 CFR 46), HHS regulations, and 2018 updates
04
Human Subjects Research & IRBs
Definitions, exempt vs non-exempt research, IRB types and membership
05
The Clinical Pharmacist's Role
Six core functions, FDA compliance duties, and barriers to integration
06
FDA Case Studies
Dr. Padilla & Dr. Lightner: Real-world Belmont violations analyzed
07
Key Takeaways & Conclusion
Four lessons, best practices, and the call to action for the field
Dr. Meghana Karnaty | Mentor: Tasha Mohseni | RD Research Services, LLC |
Northeastern University
Capstone Project Overview
Project Overview
Completed for RD Research Services, LLC in collaboration with Northeastern University Experiential Network.
Goal: Build a strong, practical understanding of human subjects research, regulatory requirements, and IRB processes.
Knowledge Acquisition: Completing OHRP training covering HHS regulations, definitions of human subjects research, and IRB standards.
Practical Translation: Creating publication-ready educational content for S.P.I.R.I.T. newsletter — breaking complex regulatory concepts into accessible language.
9-Week Capstone Timeline
Week 1
OHRP Training Completion
Week 2
Article Draft on OHRP Learnings
Week 3
Belmont Report + FDA Warning Letter Analysis
Week 4
Begin Advanced 2,000+ Word Article
Week 5
Publish Advanced Article
Week 6
Finalize Presentation
Dr. Meghana Karnaty | Mentor: Tasha Mohseni | RD Research Services, LLC |
Northeastern University
Week 1: OHRP Foundational Training
OHRP Human Research Protection Foundational Training · Considerations for Reviewing Human Subjects Research
1
When HHS Regulations Apply
Determines whether a study falls under federal oversight and Common Rule requirements.
2
Definitions of Human Subjects Research
Systematic investigations involving living individuals via interaction, intervention, or identifiable private information.
3
IRB Responsibilities & Oversight
Committees of ≥5 members (scientist, non-scientist, unaffiliated) review & approve research before it begins.
4
Independent Ethical Review
Ensures no single investigator can approve their own research.
5
Institutional Compliance
Institutions must maintain policies, train staff, and hold a Federalwide Assurance (FWA).
Considerations for Reviewing Human Subjects Research
Balancing Risks and Benefits
IRBs must weigh potential risks against scientific value — risks must never be excessive relative to benefits.
Equitable Selection of Subjects
Fair selection distributes risks and benefits equitably across appropriate populations.
Minimizing Risks in Research
Researchers must use procedures that minimize participant exposure to risk.
Protecting Privacy & Data Confidentiality
Researchers must safeguard identifiable information through secure data practices.
Dr. Meghana Karnaty | Mentor: Tasha Mohseni | RD Research Services, LLC |
Northeastern University
Week 2: OHRP Article Draft
Human Subjects Research, Regulatory Compliance, and IRB Processes
The 'Big Three' Ethical Principles
Respect for Persons — voluntary, fully-informed participation.
Beneficence — minimize harm, maximize benefit.
Justice — fair selection; no group bears unfair research burdens.
The Rules of the Road (Common Rule, 45 CFR 46)
Primary U.S. regulatory framework. Covers definitions, human subjects, and exempt categories. 2019 revision updated consent standards.
IRBs — Who Decides If Research Is Ethical?
Committees of ≥5 diverse members. Three pathways: Exempt, Expedited Review, Full Board Review. No study begins without written IRB approval.
Vulnerable Populations — Special Care Required
Children (parental permission + assent), Pregnant women/fetuses, Prisoners (extra safeguards), Cognitively impaired individuals.
Institutional Responsibility — FWA
Institutions conducting federally funded research must sign an FWA — a formal promise to follow all rules, educate staff, and maintain a functioning IRB.
"Every research decision starts with a human being who trusted the system." — Dr. Meghana Karnaty
Dr. Meghana Karnaty | Mentor: Tasha Mohseni | RD Research Services, LLC |
Northeastern University
The Belmont Report (1979)
The Ethical Foundation of Human Subjects Research
Background:
Created by the National Commission for the Protection of Human Subjects
Respect for Persons
Beneficence
Justice
Dr. Meghana Karnaty | Mentor: Tasha Mohseni | RD Research Services, LLC |
Northeastern University
The Common Rule (45 CFR 46)
Regulatory Backbone of Human Subjects Protection
What is the Common Rule?
Federal policy governing human subjects research, known as Subpart A of 45 CFR 46. Adopted by HHS, DoD, DOE, and multiple federal agencies.
Major Goals
2018 Revised Common Rule — Key Updates
1
New Exemption Categories
Eight updated exemption categories replacing the prior six-category framework for lower-risk research.
2
Reduced Continuing Review
Eliminated mandatory continuing review for certain minimal-risk and expedited studies.
3
Single IRB Requirement
Cooperative multi-site research must use a single IRB — effective January 2020.
4
Updated Consent Standards
Revised informed consent requirements with new elements and improved readability expectations.
Dr. Meghana Karnaty | Mentor: Tasha Mohseni | RD Research Services, LLC |
Northeastern University
What Is Human Subjects Research?
Research is a systematic investigation designed to contribute to generalizable knowledge involving living individuals
Interaction or Intervention
Researchers obtain information through direct interaction with participants OR access identifiable private information.
Living Individuals Required
Human subjects research involves living individuals — distinguishing it from records research on deceased persons.
Identifiable Information
If identifiable data is collected from living individuals, the activity may qualify as Human Subjects Research requiring IRB review.
Non-Research Activities
Journalism, public health surveillance, oral history, and program evaluation are generally not considered research.
Examples of HSR
Surveys, interviews, medical record reviews, biospecimen collection, and observational studies involving living participants.
IRB Determination
When in doubt, researchers should consult the IRB or HRPP office before starting any activity involving human subjects.
Dr. Meghana Karnaty | Mentor: Tasha Mohseni | RD Research Services, LLC |
Northeastern University
Exempt vs. Non-Exempt Research
✔ Exempt Research
⚠ Non-Exempt Research
Dr. Meghana Karnaty | Mentor: Tasha Mohseni | RD Research Services, LLC |
Northeastern University
Institutional Review Boards (IRBs)
Protecting Research Participants
Purpose: Protect participant rights and welfare · Ensure ethical and regulatory compliance · Review research risks and benefits
IRB Membership Requirements
Conflict of Interest Rules
Members with conflicts cannot participate in voting. Quorum requires majority attendance and at least one non-scientist present.
Types of IRB Review
Feature | Full Board Review | Expedited Review |
Risk Level | More than minimal risk | Minimal risk |
Review Method | Convened IRB meeting | Chair or designated reviewer |
Outcomes | Approve, Modify, Disapprove | Approve or Request Changes |
Continuing Review | Usually required | Often not required |
Dr. Meghana Karnaty | Mentor: Tasha Mohseni | RD Research Services, LLC |
Northeastern University
Institutional Oversight & Compliance Structures
1
Federalwide Assurance (FWA)
A formal agreement between institutions and the federal government to comply with HHS regulations for human subjects research.
2
FWA Requirement
Institutions engaged in non-exempt HHS-funded human subjects research are required to maintain an active FWA.
3
Institutional Engagement
Institutions are considered 'engaged' when they interact with participants or access identifiable private information.
4
Single IRB Requirement
The Single IRB requirement became effective January 2020. Most cooperative, multi-site research must rely on one reviewing IRB.
5
Most Cooperative Research
Must rely on a single IRB for oversight. Reliance agreements document the responsibilities of each participating institution.
6
Reliance Agreements
Document institutional responsibilities when one institution relies on another's IRB. Critical for multi-site study compliance.
Dr. Meghana Karnaty | Mentor: Tasha Mohseni | RD Research Services, LLC |
Northeastern University
Week 3
Ethical Violations in Clinical Research:
Comparing Two FDA Warning Letters
Through the Belmont Report
"Clinical research depends on trust — the trust of participants, institutions, and the public. When investigators fail to uphold that trust, the consequences are measured not in paperwork, but in human lives."
FDA Warning Letters: Dr. Americo F. Padilla · Dr. Amy Lightner · March 25, 2025
Case Study 1: Dr. Americo F. Padilla
FDA Warning Letter — March 25, 2025
⚠ VIOLATION: Protocol deviations and inadequate oversight. The investigator failed to ensure the clinical trial was conducted per the signed investigator statement and investigational plan.
Beneficence — PRIMARY (90%)
Deviating from an approved protocol removes safety guardrails. Participants may be exposed to unanticipated risks without the researcher even realizing it.
Respect for Persons — SECONDARY (65%)
Participants consent based on clearly defined procedures. When those procedures are altered without their knowledge, the original consent becomes partially invalid.
Research Integrity & Public Trust
Protocol deviations reduce data reliability and scientific validity. Each violation contributes to gradual erosion of public trust in the clinical research enterprise.
KEY QUESTION:
"Was the study conducted correctly?" · Justice Severity: Low (20%)
Dr. Meghana Karnaty | Mentor: Tasha Mohseni | RD Research Services, LLC | Northeastern University
Northeastern University
Case Study 2: Dr. Amy Lightner
FDA Warning Letter — March 25, 2025
⚠ VIOLATION: Enrollment of ineligible participants who did not meet study criteria, combined with inadequate documentation and failure to follow investigational procedures.
Justice — PRIMARY VIOLATION (95%)
Improper enrollment disrupts fair distribution of research risks and benefits. Participant selection is not applied as designed violating the foundational equity principle of Belmont.
Beneficence — HIGH CONCERN (80%)
Enrolling ineligible individuals exposes them to interventions that are not safe for their specific medical or physiological conditions the study risk profile was not established for them.
Respect for Persons — AFFECTED (55%)
Consent cannot be fully informed if eligibility status and associated risks were not properly assessed before enrollment. Also distorts study outcomes and data integrity.
KEY QUESTION:
"Should these people have been in the study at all?" · Eligibility criteria define the boundary between who a study is safe for and who it is not.
Dr. Meghana Karnaty | Mentor: Tasha Mohseni | RD Research Services, LLC |
Northeastern University
Real-World Consequences & Why FDA Oversight Matters
Common Consequences of Clinical Research Violations
Participant Safety
35%
Study Integrity
25%
Public Trust
20%
Regulatory Compliance
15%
Data Quality
5%
Why FDA Oversight Is Non-Negotiable
1
IRBs review protocols
Before enrollment — but only work with information they're given. Investigators who deviate post-approval defeat this protection entirely.
2
FDA monitors compliance
Through inspections, audits, and warning letter processes — the federal government's active responsibility to protect research participants.
3
Documentation is evidence
Incomplete records make it impossible to verify participant protection. If it isn't documented, regulators must assume it wasn't done.
4
Informed consent is ongoing
Its protective value depends on the study remaining consistent with what was originally disclosed.
Dr. Meghana Karnaty | Mentor: Tasha Mohseni | RD Research Services, LLC |
Northeastern University
Week 4
The Overlooked Role of the
Clinical Pharmacist in Research
Compliance and Patient Safety
~50% of serious adverse events in clinical trials involve medication-related issues where pharmacy expertise is critical
Comparing the Cases: Same Framework, Different Failures
Category | Dr. Padilla | Dr. Lightner |
Core Belmont Concern | Beneficence / Respect for Persons | Justice / Beneficence |
Focus Area | How the study was conducted (protocol execution) | Who was allowed to participate (eligibility) |
Participant Risk | Uncontrolled procedural risks to data and safety | Inappropriate exposure due to ineligibility |
Documentation Failure | Missing protocol adherence records | Insufficient eligibility screening records |
Justice Severity | Low (20%) | High (95%) |
Beneficence Severity | High (90%) | High (80%) |
Respect for Persons | Moderate (65%) | Moderate (55%) |
Common Ground | Both violated FDA regulations, failed to protect participants, and undermined research integrity | |
Dr. Meghana Karnaty | Mentor: Tasha Mohseni | RD Research Services, LLC |
Northeastern University
Who Is the Clinical Pharmacist?
~50%
of serious adverse events in clinical trials involve medication-related issues where pharmacy expertise is critical
Who Is a Clinical Pharmacist?
"The clinical pharmacist is not a supporting character in the story of clinical research — they are, in many cases, the plot itself. When investigational drugs are mishandled, misdosed, or inadequately monitored, it is the pharmacist's expertise that stands between a protocol deviation and a serious adverse event."
Dr. Meghana Karnaty | Mentor: Tasha Mohseni | RD Research Services, LLC |
Northeastern University
FDA Regulatory Landscape — Where Pharmacists Belong
Regulation | Key Requirement | Pharmacist Role |
21 CFR 312.61 | Drugs used only per investigational plan | Verify dispensing matches approved protocol exactly |
21 CFR 312.62 | Complete drug disposition records required | Maintain & audit dispensing logs and destruction documentation |
21 CFR 312.64 | Adverse effect reporting obligations | Identify, document, and support AE attribution to drugs vs disease |
GCP ICH E6 | Good Clinical Practice for investigational products | Ensure storage, handling, labeling and dispensing meet GCP standards |
21 CFR 211 | Current Good Manufacturing Practice | Apply cGMP knowledge to investigational compound handling |
⚠ Many violations in FDA warning letters — inadequate drug accountability, storage failures, improper administration — are problems a qualified pharmacist would have been positioned to prevent.
Dr. Meghana Karnaty | Mentor: Tasha Mohseni | RD Research Services, LLC |
Northeastern University
The Six Core Roles of the Clinical Pharmacist in Research
1
Investigational Product Management
Receives, stores, prepares, dispenses, and documents all investigational products. Ensures cold chain, expiration monitoring, and accountability log accuracy.
2
Protocol Compliance Verification
Before dispensing, independently verifies patient eligibility, required assessments, and dose specifications — the final compliance checkpoint.
3
Adverse Event Detection & Attribution
Applies pharmacokinetic expertise to distinguish drug-related from disease-related adverse events for accurate FDA, DSMB, and IRB safety reporting.
4
Drug Interaction Screening
Screens for interactions between investigational products and concomitant medications that could compromise safety or confound study results.
5
Informed Consent Support
Explains medication risks, administration procedures, and side effects in accessible language — directly supporting Belmont's Respect for Persons principle.
6
Regulatory Documentation & Audit Readiness
Maintains drug accountability records, temperature logs, and dispensing documentation that FDA inspectors review during site audits.
Dr. Meghana Karnaty | Mentor: Tasha Mohseni | RD Research Services, LLC |
Northeastern University
Belmont Principles & Pharmacy Expertise
How the clinical pharmacist's expertise maps directly onto each of the three Belmont principles
Respect for Persons
PHARMACY ROLE
Pharmacists ensure participants receive accurate, understandable information about their medications supporting truly informed, voluntary consent.
VIOLATION SEVERITY
Padilla: Moderate (65%)
Lightner: Moderate (55%)
Beneficence
PHARMACY ROLE
Through drug interaction screening, adverse event monitoring, and protocol compliance, pharmacists directly minimize participant harm and maximize safety of investigational interventions.
VIOLATION SEVERITY
Padilla: High (90%)
Lightner: High (80%)
Justice
PHARMACY ROLE
Pharmacists help ensure consistent, equitable dosing across all participants, preventing disparities in how investigational products are administered to different patient populations.
VIOLATION SEVERITY
Padilla: Low (20%)
Lightner: High (95%)
Dr. Meghana Karnaty | Mentor: Tasha Mohseni | RD Research Services, LLC |
Northeastern University
Barriers to Pharmacist Integration in Research
Scope of Practice Ambiguity
The clinical pharmacist's research role is undefined or informal in many institutions — involvement depends on individual initiative rather than institutional mandate.
Funding Challenges
Clinical trial budgets rarely include a dedicated pharmacy staff line item. Pharmacy involvement is treated as optional until a regulatory inspection reveals its cost.
Lack of Formal Research Training
Few PharmD programs include formal coursework in GCP, FDA regulations, or clinical trial management — limiting pharmacists' authority in research settings.
Hierarchical Team Dynamics
Research teams are frequently physician-led. Building a culture where pharmacy expertise is actively sought requires deliberate institutional leadership.
Regulatory Silence
FDA regulations require drug accountability but do NOT specifically mandate pharmacist involvement — allowing non-pharmacists to perform pharmacy functions without explicit violation.
Dr. Meghana Karnaty | Mentor: Tasha Mohseni | RD Research Services, LLC |
Northeastern University
Key Takeaways for Every Researcher
01
Protocol Is Protection
Every line of an approved protocol exists for a reason. Deviating — even with good intentions — removes protections participants were promised and regulators approved.
02
Eligibility Is Ethics
Inclusion and exclusion criteria are not administrative hurdles. They define the boundary between who a study is safe for and who it isn't. Ignoring them is direct harm.
03
Pharmacy Is Infrastructure
Investigational drug management is a specialized clinical and regulatory responsibility. Formal pharmacist designation on every research team is essential, not optional.
04
Advocacy Starts with Visibility
Clinical pharmacists must advocate for their inclusion in research governance, protocol development, and regulatory submissions. Visibility is the first step toward structural integration.
05
Document Everything
Inadequate documentation isn't just a compliance issue — it makes it impossible to demonstrate participants were protected. If it isn't documented, regulators must assume it wasn't done.
06
IRBs Are Partners, Not Gatekeepers
The relationship between investigators and IRBs should be collaborative. The IRB's job is to help researchers protect participants — not just approve paperwork and disappear.
Dr. Meghana Karnaty | Mentor: Tasha Mohseni | RD Research Services, LLC |
Northeastern University
Conclusion
Seen, Valued, and Structurally Integrated
The Belmont Report's principles, the Common Rule's requirements, and the clinical pharmacist's expertise all converge on a single obligation: protecting every person who volunteers their body and time to advance science. From the IRB reviewing a protocol before enrollment to the pharmacist catching a drug interaction at the point of dispensing, every layer of the research protection system depends on experts doing their job with integrity and visibility.
The Belmont Report Still Matters
Respect for Persons, Beneficence, and Justice are the active standards against which every FDA audit and IRB review is measured today.
Compliance Is Not Optional
Warning letters issued to Padilla and Lightner are reminders of what it costs when the investigator's duty to protect participants is not honored.
Make Pharmacy Visible
Institutions, sponsors, IRBs, and regulators must make pharmacy involvement an explicit expectation — not an informal courtesy.
Dr. Meghana Karnaty | Mentor: Tasha Mohseni | RD Research Services, LLC | Northeastern University Experiential Network