Week 2 Overview

21 CFR PART 50: Protection of Human Subjects and Informed Consent

SOCRA CCRP Exam Comprehensive Reference Guide

Target Audience: Clinical Research Professionals with Implementation Science backgrounds
Last Updated: October 2025
Exam Coverage: 15-25% of SOCRA CCRP Certification Exam

1. 21 CFR Part 50 Overview

Regulatory Framework

21 CFR Part 50 establishes FDA requirements for obtaining and documenting informed consent from human subjects participating in FDA-regulated clinical investigations.

Applicability:

• APPLIES TO: IND drug studies, IDE device studies, biological product investigations
• DOES NOT APPLY TO: Implementation science (non-IND/IDE), quality improvement projects
• MAY ALSO APPLY: 45 CFR 46 if HHS-funded

Key Sections

Recent Updates (2023-2025)

🆕 January 22, 2024: FDA Final Rule on §50.22

• Expanded waiver/alteration criteria for minimal risk research
• Now includes identifiable private information and biospecimens
• Must be impracticable without identifiable format

🆕 March 2024: Joint FDA/OHRP Draft Guidance

• "Key Information and Facilitating Understanding in Informed Consent"
• Emphasizes concise presentation of material information upfront

🆕 2025: Accessibility Updates

• Enhanced requirements for limited English proficiency
• Title VI Civil Rights Act compliance for HHS-funded research

🆕 ICH E6(R3): Finalized 2024, SOCRA Exam Transition January 2026

• eConsent provisions
• Remote consent processes
• Risk-proportionate approaches

2. The 8 Basic Elements of Informed Consent (§50.25(a))

🔥 CRITICAL FOR SOCRA EXAM

These 8 elements are MANDATORY for all FDA-regulated research unless exception applies (§§50.23, 50.24).
Exam Weight: 15-20% of questions

📌 MNEMONIC: "RPRB-CCVC"

Research | Procedures | Risks | Benefits
Confidentiality | Compensation* | Voluntary | Contact

*Element 6 (Compensation) required ONLY for >minimal risk research

Element 1: Research Statement [§50.25(a)(1)]

Requirement: Statement that study involves research, explanation of purposes, expected duration, procedures description, identification of experimental procedures.

Must Include:

• ✅ Explicit word "research" or "study"
• ✅ Purpose/objectives in lay language
• ✅ How long subject will participate (specific timeline)
• ✅ ALL procedures to be performed
• ✅ Which procedures are EXPERIMENTAL (vs. standard care)
• ✅ Frequency of visits/procedures

Common Violations:

• ❌ Omits "research" - just describes as "treatment program"
• ❌ Doesn't distinguish experimental from standard care
• ❌ Vague duration: "several visits" instead of "12 weeks, 8 visits"
• ❌ Missing experimental procedure identification

SOCRA Exam Focus:

• Can you identify when research vs. standard care is unclear?
• Are experimental procedures clearly labeled?
• Is the timeline specific enough?

Example - GOOD:

"This is a research study to test whether a new drug called XYZ-123 can lower blood pressure better than standard treatments. If you agree to participate, you will be in this study for approximately 6 months and will be asked to attend 10 study visits. During these visits, you will have blood drawn, complete questionnaires, and undergo physical exams. Taking the study drug XYZ-123 is experimental and is not approved by the FDA."

Example - BAD:

"This program will help treat your high blood pressure. You'll come in for visits and testing."
❌ Missing: research statement, duration, procedure details, experimental disclosure

Element 2: Risks and Discomforts [§50.25(a)(2)]

Requirement: Description of any reasonably foreseeable risks or discomforts to the subject.

Must Include:

• ✅ Physical risks: Side effects, adverse reactions, pain, medical complications
• ✅ Psychological risks: Stress, anxiety, emotional distress, traumatic recall
• ✅ Social risks: Stigma, discrimination, social consequences
• ✅ Economic risks: Time commitment, potential income loss
• ✅ Privacy risks: Breach of confidentiality, inadvertent disclosure
• ✅ Reproductive risks: Risks to embryo/fetus if subject becomes pregnant
• ✅ Common risks AND rare but serious risks
• ✅ Risks that may worsen existing conditions

Common Violations:

• ❌ Lists only physical risks, omits psychological/social
• ❌ Minimizes: "This drug is generally safe with minimal side effects"
• ❌ Omits pregnancy risks for women of childbearing potential
• ❌ Fails to update as new safety data emerges
• ❌ Doesn't disclose placebo group may not receive active treatment

SOCRA Exam Focus:

• What risk category is missing (physical/psych/social)?
• Are pregnancy-related risks addressed?
• For women of childbearing age, is contraception requirement stated?
• Are risks to future insurability or employment mentioned if applicable?

Risk Categories Checklist:

□ Physical/Medical
□ Psychological/Emotional  
□ Social (stigma, discrimination)
□ Economic (time, costs)
□ Privacy/Confidentiality
□ Pregnancy/Reproductive
□ Genetic (if applicable)

Element 3: Benefits [§50.25(a)(3)]

Requirement: Description of any benefits to subject or others reasonably expected from research.

Must Include:

• ✅ Potential direct benefits to subject (if any)
• ✅ Realistic expectations (no overpromising)
• ✅ Societal/scientific benefits (knowledge gained)
• ✅ Statement if NO direct benefit expected (Phase I, observational studies)
• ✅ Clarification that payment is NOT a benefit

Common Violations:

• ❌ Therapeutic misconception: "This treatment will cure your disease"
• ❌ Guarantees benefits: "You will experience improvement"
• ❌ Omits "no direct benefit" in non-therapeutic research
• ❌ Lists payment as a "benefit to you"
• ❌ Implies guaranteed access to experimental treatment

SOCRA Exam Focus:

• Can you identify therapeutic misconception?
• Is "no direct benefit" statement present when required?
• Are benefits realistically described without overpromising?
• Is payment correctly described under Element 8, not as "benefit"?

Example - GOOD (No Direct Benefit):

"You may not receive any direct medical benefit from being in this study. The information we learn from this study may help future patients with your condition. The medical tests performed as part of this study may provide information about your health status, but this is not the purpose of the research."

Example - BAD:

"This experimental drug will improve your symptoms and you'll receive free medical care worth thousands of dollars."
❌ Overpromises benefits, conflates study procedures with "free care"

Element 4: Alternatives [§50.25(a)(4)]

Requirement: Disclosure of appropriate alternative procedures or treatments that might be advantageous to subject.

Must Include:

• ✅ Available standard-of-care treatments for the condition
• ✅ Option to receive standard care outside the study
• ✅ Non-participation as an alternative
• ✅ For device studies: existing approved devices
• ✅ Sufficient detail for informed comparison
• ✅ Statement if no alternatives exist

Common Violations:

• ❌ Omits standard treatments entirely
• ❌ Doesn't mention that non-participation is an option
• ❌ Insufficient detail: "Other treatments exist" without naming them
• ❌ Biased presentation favoring research participation
• ❌ Implies no alternatives when they exist

SOCRA Exam Focus:

• Is non-participation listed as an alternative?
• Are standard treatments adequately described with sufficient detail?
• Is presentation balanced (not biased toward enrollment)?

Example - GOOD:

"Instead of being in this study, you have these options:

1. Do not participate: You can choose not to be in this study. Your regular doctor can treat your condition with standard medications.
2. Standard medications: FDA-approved drugs for high blood pressure include ACE inhibitors (like lisinopril), beta-blockers (like metoprolol), and calcium channel blockers (like amlodipine). Your doctor can discuss which is best for you.
3. Lifestyle changes: Diet, exercise, and weight loss can lower blood pressure.

Your doctor can explain these options in more detail."

Element 5: Confidentiality [§50.25(a)(5)]

Requirement: Statement describing extent of confidentiality and noting FDA may inspect records.

Must Include:

• ✅ Extent of confidentiality protections
• ✅ Who will have access: sponsor, IRB, FDA, other parties
• ✅ EXPLICIT statement that FDA may inspect records 🔥
• ✅ Certificate of Confidentiality (if applicable)
• ✅ How data will be stored and protected
• ✅ Data sharing plans or publication plans
• ✅ Use of coded data vs. identifiable data
• ✅ How long records will be kept

Common Violations:

• ❌ FAILS TO MENTION FDA INSPECTION ← Most common exam question!
• ❌ Promises "absolute confidentiality" (impossible to guarantee)
• ❌ Doesn't disclose sponsor access to identifiable data
• ❌ Missing HIPAA Authorization when separately required
• ❌ Vague: "Your information will be kept private" without details

SOCRA Exam Focus:

• FDA INSPECTION DISCLOSURE IS MANDATORY - frequently tested!
• Can you identify when confidentiality promises are too absolute?
• Is sponsor access clearly disclosed?

Example - GOOD:

"We will keep your study information confidential to the extent permitted by law. However, some people and organizations may inspect your research records:

• The study sponsor (XYZ Pharmaceuticals)
• The Institutional Review Board (IRB) that approved this study
• The Food and Drug Administration (FDA)
• Government agencies in other countries where the drug may be submitted for approval

We will store your information in locked cabinets and password-protected computers. Your name will not be used in any reports or publications. You will be identified only by a code number.

There is a small risk that someone outside the study could get access to your private health information."

Example - BAD:

"Your information will be kept completely confidential."
❌ Absolute promise impossible; missing FDA inspection; insufficient detail

Element 6: Compensation and Medical Treatment for Injury [§50.25(a)(6)]

Requirement: For research involving >minimal risk: explanation of whether compensation/medical treatments available if injury occurs, what they consist of, or where to obtain information.

⚠️ CRITICAL: Required ONLY for greater than minimal risk research

Must Include (when >minimal risk):

• ✅ Whether compensation will be provided for research-related injury
• ✅ Whether medical treatment will be provided/available
• ✅ What treatments/services are covered vs. not covered
• ✅ Contact information for questions or to obtain treatment
• ✅ Who will pay for treatment (if applicable)
• ✅ Process for seeking compensation

Common Violations:

• ❌ Completely omitted in >minimal risk study ← Automatic violation
• ❌ Vague: "Standard medical care is available"
• ❌ Unclear what injuries qualify for compensation
• ❌ Exculpatory language: "You give up your right to compensation"
• ❌ Implies subject must prove negligence for treatment

SOCRA Exam Focus:

• When is this element required? (Only >minimal risk!)
• What level of detail is necessary?
• Can you distinguish compensation vs. treatment?

Example - GOOD (>Minimal Risk with Treatment Available):

"If you are injured as a direct result of being in this study, medical treatment is available at [Hospital Name]. The costs of this treatment may be covered by the study sponsor or may be billed to you or your insurance company, depending on your specific insurance plan and the nature of the injury. You do not give up any legal rights by signing this consent form. For more information about compensation or treatment for injury, contact [Name] at [Phone]."

Example - GOOD (>Minimal Risk, No Compensation):

"If you are injured as a result of being in this study, treatment will be available. The costs of the treatment may be billed to you or your insurance. No funds have been set aside to compensate you in the event of injury."

Example - Minimal Risk Study:

[Element 6 not required - can be omitted]

Element 7: Contact Information [§50.25(a)(7)]

Requirement: Explanation of whom to contact for: (1) questions about research and subjects' rights, and (2) research-related injury.

Must Include - MINIMUM TWO CONTACTS:

• ✅ Contact for RESEARCH questions (PI, research coordinator)
• ✅ Separate contact for RIGHTS questions (IRB, independent contact)
• ✅ 24/7 emergency contact (if study involves emergencies or after-hours events)
• ✅ Contact for research-related injury (can be same as research contact)
• ✅ Names, phone numbers, and availability

Common Violations:

• ❌ Only provides PI contact, omits IRB/rights contact
• ❌ No emergency contact for 24/7 or inpatient studies
• ❌ Outdated or incorrect contact information
• ❌ Doesn't distinguish research questions from rights questions
• ❌ Lists only daytime numbers when study involves weekends/nights

SOCRA Exam Focus:

• TWO separate contacts required minimum: research AND rights
• Exam frequently tests this distinction
• Is emergency contact provided when appropriate?

Example - GOOD:

"Questions about the study: If you have questions about this research, contact:

• Dr. Jane Smith, Principal Investigator: (555) 123-4567 (Monday-Friday, 8am-5pm)
• Sarah Johnson, Research Coordinator: (555) 123-4568 (Monday-Friday, 8am-5pm)
• 24-hour emergency pager: (555) 999-9999

Questions about your rights: If you have questions or concerns about your rights as a research participant, contact:

• Office of Human Research Protection: (555) 555-5555
• IRB@institution.edu"

Example - BAD:

"Contact Dr. Smith at 555-1234 if you have questions."
❌ No IRB/rights contact; no emergency contact; insufficient detail

Element 8: Voluntary Participation Statement [§50.25(a)(8)]

Requirement: Statement that participation is voluntary, refusal involves no penalty or loss of benefits, subject may withdraw anytime without penalty or loss of benefits.

Must Include:

• ✅ Participation is voluntary
• ✅ May refuse to participate without penalty
• ✅ May withdraw at any time without penalty
• ✅ No loss of benefits subject is otherwise entitled to
• ✅ How to withdraw (process/procedure)
• ✅ Consequences of withdrawal (if any)

Common Violations:

• ❌ Subtle coercion: "Refusing may limit future treatment options here"
• ❌ Doesn't explain HOW to withdraw
• ❌ Implies continued medical care depends on participation
• ❌ Suggests negative consequences for non-participation
• ❌ For students/employees: doesn't clarify no impact on grades/employment

SOCRA Exam Focus:

• Can you identify subtle coercion or undue influence?
• Is withdrawal process clearly explained?
• Are "otherwise entitled benefits" properly described?

Example - GOOD:

"Taking part in this study is completely voluntary. You may choose not to participate or you may leave the study at any time. Your decision will not result in any penalty or loss of benefits to which you are entitled.

If you decide to leave the study, please contact Dr. Smith at 555-1234. We may ask you to return for a final safety visit, but you are not required to do so.

Your current and future medical care at [Hospital Name] will not be affected by your decision to participate or not participate in this research study."

Example - BAD (Subtle Coercion):

"You are free to withdraw, but doing so may affect your access to the study doctors and tests."
❌ Implies withdrawal has negative consequences; coercive

Example - BAD (Student Context):

"Participation is voluntary and your grade won't be affected."
⚠️ Better, but should clarify alternative assignment available for non-participants

3. Additional Elements (§50.25(b))

These 6 elements are required "when appropriate" - they become mandatory when the circumstances apply.

Additional Element 1: Unforeseeable Risks [§50.25(b)(1)]

When Required: Treatment/procedure may involve risks currently unforeseeable; or risks to embryo/fetus

Example:

"The study drug may have side effects that are not yet known. If you are pregnant or become pregnant during this study, the study drug may have unknown effects on your unborn baby. Tell the study doctor immediately if you become pregnant."

Additional Element 2: Anticipated Termination Circumstances [§50.25(b)(2)]

When Required: Investigator may terminate subject's participation without consent

Example:

"The study doctor may remove you from this study without your permission if:

• Your disease gets worse
• You do not follow study procedures
• The study is stopped by the sponsor or FDA
• The study doctor believes it is in your best interest"

Additional Element 3: Additional Costs [§50.25(b)(3)]

When Required: Participation may result in added costs to subject

Example:

"Your insurance company or you will be responsible for the costs of your regular medical care that you would have even if you were not in the study. These costs may include:

• Routine office visits
• Standard lab tests
• Medications for other conditions You will also be responsible for parking and travel costs to and from study visits."

Additional Element 4: Consequences of Withdrawal [§50.25(b)(4)]

When Required: There are consequences of withdrawing OR procedures needed for orderly termination

Example:

"If you decide to stop taking the study drug, you should tell the study doctor right away. You may need to taper off the medication slowly to avoid withdrawal symptoms. You should return for a final safety visit within 30 days of your last dose. During this visit, we will check your blood pressure and ask about any side effects."

Additional Element 5: Significant New Findings [§50.25(b)(5)]

When Required: Nearly always (standard practice)

Example:

"If we learn any important new information during the study that might affect your willingness to continue participating, we will tell you about it as soon as possible."

Additional Element 6: Number of Subjects [§50.25(b)(6)]

When Required: When appropriate (increasingly standard practice)

Example:

"Approximately 300 people will take part in this study. About 40 study sites in the United States will enroll patients."

4. Exceptions from Informed Consent

Exception 1: Emergency Research - 21 CFR 50.24

Purpose: Allows research in life-threatening emergencies when subjects unable to consent and LAR not available

ALL 8 Criteria Must Be Met:

1. ✅ Subjects in life-threatening situation; available treatments unproven/unsatisfactory
2. ✅ Evidence collection necessary to determine safety/effectiveness
3. ✅ Obtaining consent not feasible because:
   • Subjects unable to consent due to medical condition, AND
   • Intervention must be administered before LAR consent feasible, AND
   • No reasonable way to prospectively identify eligible subjects
4. ✅ Participation provides prospect of direct benefit to subjects
5. ✅ Research could not practicably be carried out without waiver
6. ✅ Study defines therapeutic window; investigator will attempt to contact LAR within window
7. ✅ IRB approved consent procedures for use when feasible
8. ✅ Additional protections:
   • Community consultation before and during research
   • Public disclosure before and after research
   • Independent data monitoring committee
   • Attempt to contact family if LAR unavailable (to ask about objections)

SOCRA Exam Scenario:

A study tests a new treatment for severe traumatic brain injury in unconscious patients arriving at emergency departments. Consent under §50.24?

Analysis: May qualify if:

• Standard treatments inadequate ✓
• Subjects unconscious, can't consent ✓
• Must treat within narrow window ✓
• Direct benefit to subjects ✓
• Community consultation completed ✓
• Public disclosure performed ✓
• Data monitoring committee established ✓

Exception 2: Waiver/Alteration for Minimal Risk - 21 CFR 50.22

NEW 2024 Expansion: Now includes identifiable private information and biospecimens

IRB May Waive/Alter Consent if ALL Met:

1. ✅ Research involves no more than minimal risk
2. ✅ Research could not practicably be carried out without waiver/alteration
3. ✅ If using identifiable data/biospecimens: could not practicably be done without identifiable format
4. ✅ Waiver/alteration will not adversely affect rights and welfare of subjects
5. ✅ Whenever appropriate: Subjects provided pertinent information after participation

Common Use Cases:

• Retrospective chart reviews (minimal risk, impractical to contact all patients)
• Analysis of existing biospecimens for research purposes
• Emergency department observational studies of standard care

Exception 3: Single Patient Emergency Use - 21 CFR 50.23

Different from §50.24! This is for treating ONE patient (expanded access), not research protocol.

Consent Waived When BOTH:

• Patient unable to give informed consent (unconscious, lacks capacity)
• Time insufficient to obtain consent from LAR

Example: Compassionate use of investigational drug for dying patient who is unconscious.

5. Vulnerable Populations Framework

45 CFR 46 Overview

While 21 CFR 50 governs FDA-regulated research, 45 CFR 46 provides additional protections for vulnerable populations in HHS-supported research.

Subpart Structure:

• Subpart A: Common Rule (basic protections - all research)
• Subpart B: Pregnant women, fetuses, neonates
• Subpart C: Prisoners
• Subpart D: Children

Children: 45 CFR 46 Subpart D

Definition: Individual who has not attained legal age for consent (typically <18 years)

Four Categories of Research - Must Fit One

*Unless one parent deceased, unknown, incompetent, or not reasonably available

Assent Requirements

What is Assent?

• Child's affirmative agreement to participate
• Different from consent (which LAR provides)
• IRB determines if children capable of assenting based on age, maturity, psychological state

When Required:

• Generally required for children capable of assenting (typically 7+ years)
• IRB determines capacity based on study complexity and child characteristics

When Assent Can Be Waived:

• Child not capable of assenting
• Intervention offers prospect of direct benefit not available outside research
• Research involves only minimal risk

Respecting Dissent:

• Child's objection ("dissent") must be respected
• Exception: Intervention necessary for child's welfare AND available only in research context

Special Protections for Wards

Ward: Child under state/agency custody

Restrictions (§46.409):

• Wards can only be included in research under §406 or §407 if:
  1. Research related to their status as wards, OR
  2. Conducted in settings where majority of children are NOT wards (schools, camps, hospitals)

Additional Requirement:

• IRB must appoint advocate for each ward
• Advocate acts in best interest of child
• Cannot be associated with research, investigator, or guardian organization

Pregnant Women: 45 CFR 46 Subpart B

Applicability: Research involving:

• Pregnant women
• Fetuses
• Neonates of uncertain viability
• Nonviable neonates

Key Requirements

Preclinical Studies:

• When scientifically appropriate, must conduct studies on pregnant animals first
• Clinical studies on non-pregnant women should precede (when appropriate)

Risk/Benefit Analysis:

• Risk to fetus must be caused solely by interventions with prospect of direct benefit to woman OR fetus, OR
• Risk to fetus no greater than minimal AND purpose is important biomedical knowledge not obtainable by other means

Father's Consent:

• Required when research presents >minimal risk with NO prospect of direct benefit to woman or fetus
• Exceptions:
  • Pregnancy resulted from rape or incest
  • Father unknown, unavailable, or incompetent

Prohibited Activities:

• No inducements (monetary or otherwise) to terminate pregnancy
• Researchers have no role in decisions about timing/method/procedures for termination
• Researchers have no role in determining viability of neonate

Neonates

Viable Neonate:

• After delivery, determined to be viable
• Research governed by Subpart A (and Subpart D if also classified as "child")

Nonviable Neonate:

• Must meet all Subpart B requirements
• Legally effective informed consent of both parents required
• Exception: Consent of one parent sufficient if other unavailable/incompetent/temporary incapacity
• Father's consent not required if pregnancy resulted from rape/incest

Prisoners: 45 CFR 46 Subpart C

Definition: Individual involuntarily confined or detained in penal institution

Includes:

• Individuals in prisons, jails, detention centers
• Individuals involuntarily confined for treatment of psychiatric/substance abuse disorders
• Individuals convicted of crimes but residing in community programs (if restricted)

IRB Composition Requirements

Majority NOT associated with prison:

• Most IRB members cannot be associated with the prison (employees, officials, etc.)

Prisoner Representative:

• At least one member must be a prisoner or prisoner representative

Permissible Research

Research with prisoners limited to:

(A) Study of possible causes, effects, processes of incarceration and criminal behavior

(B) Study of prisons as institutional structures or prisoners as incarcerated persons

(C) Research on conditions particularly affecting prisoners as a class (e.g., vaccine trials for diseases prevalent in prisons)

(D) Research on practices aimed at improving health/well-being of prisoners

IRB Findings Required

IRB must find:

1. ✅ Risks commensurate with risks to non-prisoner volunteers
2. ✅ Selection fair and immune from arbitrary intervention by prison authorities
3. ✅ Information presented in language understandable to prisoner population
4. ✅ Parole consideration unaffected by participation (or lack thereof)
5. ✅ If follow-up required after release, adequate provisions for this
6. ✅ Risks primarily medical conditions being studied (not risks of incarceration)
7. ✅ No coercion or undue influence (special concern in correctional settings)

OHRP Approval

• Required before NIH/HHS-supported research with prisoners can begin
• Institution must submit certification to OHRP
• OHRP reviews and provides written approval

6. ICH E6(R3) Updates on Informed Consent

Overview

ICH E6(R3) finalized in 2024; SOCRA exam content transitions January 1, 2026.

Major Shift: Risk-proportionate, quality-by-design approach that recognizes:

• Decentralized clinical trials (DCTs)
• Digital tools and technologies
• Pragmatic trial designs
• Remote and hybrid models

Electronic Consent (eConsent)

E6(R3) Section 2.8.7: Confirmation that electronic methods can be used to obtain informed consent

Key Features

📱 Multimedia Tools:

• Videos to explain complex procedures
• Animations to illustrate drug mechanisms
• Interactive quizzes to assess comprehension
• Audio narration for accessibility

💻 Remote Consent:

• Video conferencing for consent discussion
• Screen sharing to review consent documents together
• Electronic signature capture
• Especially valuable for decentralized trials

✍️ Electronic Signatures:

• Must comply with applicable regulations (e.g., 21 CFR Part 11 in US)
• Biometric signatures acceptable where permitted
• Time/date stamp automatically captured

♿ Accessibility Requirements:

• Compatible with screen readers for visually impaired
• Closed captioning for videos
• Multiple language options
• Adjustable text size and contrast

✅ Comprehension Checks:

• Embedded knowledge checks before signing
• Ability to review sections multiple times
• Progress tracking (which sections reviewed)
• Cannot proceed without viewing required sections

📋 Version Control:

• Automatic tracking of document versions
• Audit trail of all changes
• Date/time stamps for every action
• Secure storage and retrieval

Consent Process Enhancements (E6(R3))

Flexibility in Tailoring (Section 2.8.10):

• Consent elements can be included "as applicable"
• Not all elements required for all study types
• Risk-proportionate approach

Three New Consent Elements Added:

• (m) [New element - check final E6(R3) document for details]
• (n) [New element]
• (v) [New element]

Assent Clarification (Section 2.8.12):

• Minors should provide assent where appropriate
• Process should be developmentally appropriate

Key Differences: E6(R2) vs. E6(R3)

7. Common SOCRA Exam Question Patterns

Pattern 1: "What Is Missing?" Questions

Format: Presents incomplete consent form excerpt, asks what required element is missing

Example:

"A consent form states: 'This study will test a new diabetes drug. You will take pills daily for 12 weeks and come to the clinic 6 times. The drug may cause nausea or headache. This may help scientists develop better treatments. Your records will be kept private. You can stop participating anytime.' What is MISSING?"

Analysis Process:

1. Check each of 8 basic elements:
   • ✅ Research statement (Element 1)
   • ✅ Risks (Element 2)
   • ❓ Benefits (Element 3) - vague, could be better
   • ❌ Alternatives (Element 4) - MISSING
   • ❓ Confidentiality (Element 5) - doesn't mention FDA inspection
   • ❓ Compensation (Element 6) - is study >minimal risk?
   • ❌ Contact info (Element 7) - MISSING
   • ❓ Voluntary (Element 8) - incomplete

Common Correct Answers:

• Missing FDA inspection disclosure (Element 5)
• Missing alternatives (Element 4)
• Missing contact information (Element 7)
• Missing compensation statement (Element 6 if >minimal risk)

Pattern 2: Exculpatory Language

Format: Presents problematic consent language, asks if it's acceptable

Red Flags - ALWAYS PROHIBITED:

• "You give up your right to sue..."
• "You waive all claims..."
• "The hospital/sponsor is not responsible for..."
• "By signing, you release the investigator from liability..."

Example Question:

"A consent form includes: 'By signing this document, you agree that you will not hold the sponsor liable for any injuries that occur during the study.' This language is: A) Required for >minimal risk studies B) Acceptable if initialed separately
C) Exculpatory and prohibited D) Required by 21 CFR 50.27"

Answer: C - Exculpatory language is prohibited by §50.20

Pattern 3: Vulnerable Populations

Format: Scenario involving children, pregnant women, or prisoners; asks about consent requirements

Children Questions:

Example:

"A study enrolls 12-year-old children with ADHD to test a new medication. The study involves >minimal risk but offers prospect of direct benefit to subjects. What is required?"

Answer: 45 CFR 46.405 research

• One parent's permission required
• Child's assent required
• Qualifies as direct benefit research

Key Decision Points:

• One parent vs. both parents?
  • One parent: §404 (minimal risk) or §405 (direct benefit)
  • Both parents: §406 (>minimal risk, no benefit) or §407 (needs HHS approval)

Pregnant Women Questions:

Example:

"Research involves pregnant women and presents more than minimal risk with no prospect of direct benefit to the woman or fetus. Is the father's consent required?"

Answer: YES - Father's consent required (unless pregnancy from rape/incest or father unknown/unavailable)

Prisoner Questions:

Example:

"An IRB is reviewing a study that will enroll prisoners. What is required for the IRB composition?"

Answer:

• Majority of IRB cannot be associated with prison
• At least one prisoner or prisoner representative must be on IRB

Pattern 4: Exception Criteria

Format: Emergency research scenario; asks if exception applies or what's required

21 CFR 50.24 Questions:

Example:

"An ED study of septic shock treatment will enroll unconscious patients without consent. Which is NOT required under §50.24?" A) Community consultation B) FDA pre-approval of the research plan C) Independent data monitoring committee D) Public disclosure after study completion

Answer: B - FDA does not provide pre-approval; IRB approval with findings is required

Common Misconceptions:

• ❌ FDA approves §50.24 research in advance (NO - IRB approves; FDA is notified)
• ❌ Community consultation is optional (NO - required before AND during)
• ❌ Can waive consent for convenience (NO - strict criteria must be met)

Pattern 5: Documentation Requirements

Format: Asks about proper consent documentation or short form requirements

Short Form Questions (§50.27(b)(2)):

Example:

"When using short form written consent, who must sign the short form itself?"

Answer: The subject (or LAR) signs the short form. The witness signs both the short form AND the summary.

Key Points:

• Short form states elements were presented orally
• Requires witness to oral presentation
• IRB must approve written summary
• Witness signs short form + summary
• Person obtaining consent signs summary
• Subject signs short form only

8. Practice Questions with Detailed Explanations

Question 1: Basic Elements

A Phase III oncology trial consent form contains the following: statement that it's research, detailed procedures, risk disclosure, benefits statement, alternatives, confidentiality statement including "study data may be reviewed by the sponsor," contact information for the PI and IRB, and voluntary participation statement. For a study involving greater than minimal risk, what is MISSING?

A) Statement that FDA may inspect records
B) Compensation/treatment information for injuries
C) Both A and B
D) Nothing is missing

Answer: C - Both A and B

Explanation:

• Element 5 (Confidentiality) requires explicit statement that FDA may inspect records. Mentioning only "sponsor" is insufficient.
• Element 6 (Compensation) is required for >minimal risk studies. Must state whether compensation/treatment available for injuries.
• Even though 6 other elements are present, these two critical omissions make the consent form non-compliant.

SOCRA Exam Tip: FDA inspection disclosure is one of the most frequently tested elements. Never assume it's implied by mentioning "sponsor" or "IRB" - must explicitly state FDA.

Question 2: Exculpatory Language

Which of the following statements would be considered exculpatory and therefore PROHIBITED in an informed consent form?

A) "Signing this form does not waive any of your legal rights."
B) "You do not give up any legal rights by signing this consent form."
C) "By participating in this study, you agree not to pursue legal action against the institution for any injuries that may occur."
D) "The sponsor will provide compensation for injuries directly caused by the study drug."

Answer: C

Explanation:

• Statement C is exculpatory because it appears to waive the subject's right to legal action for injuries.
• Statements A and B are acceptable - they clarify that legal rights are NOT waived.
• Statement D is acceptable - it describes what compensation IS available (not waiving rights).
• Per 21 CFR 50.20: Consent may not include language that waives or appears to waive subject's legal rights or releases investigator, sponsor, or institution from liability.

SOCRA Exam Tip: Look for phrases like "agree not to sue," "waive claims," "release from liability," or "sponsor not responsible." These are always prohibited.

Question 3: Children Research Categories

A pediatric asthma study enrolls children ages 8-12. The study involves pulmonary function testing (PFTs) and blood draws. The risk is minor increase over minimal, there is no prospect of direct benefit to individual subjects, but the research may yield generalizable knowledge about childhood asthma. This research is categorized under which 45 CFR 46 Subpart D section?

A) §46.404 (minimal risk)
B) §46.405 (prospect of direct benefit)
C) §46.406 (no benefit but generalizable knowledge)
D) §46.407 (requires HHS Secretary approval)

Answer: C - §46.406

Explanation:

• Risk is "minor increase over minimal" - rules out §404
• NO direct benefit to individual subjects - rules out §405
• Will yield generalizable knowledge about the subjects' condition (asthma) - fits §406
• Does not require HHS Secretary approval (unlike §407)

Requirements for §406 research:

• ✅ Both parents' permission required (unless exception applies)
• ✅ Child's assent required
• ✅ IRB must find risk is minor increase over minimal
• ✅ Must yield generalizable knowledge about the disorder/condition

SOCRA Exam Tip: §406 is "no benefit but important knowledge" category. Both parents required (stricter than §404/§405).

Question 4: Emergency Research Exception

A proposed study will test a new treatment for out-of-hospital cardiac arrest. Patients will be unconscious and treatment must begin within 10 minutes. The study plans to enroll patients without consent under 21 CFR 50.24. Which of the following is NOT required?

A) Independent data monitoring committee
B) Community consultation before starting enrollment
C) FDA must review and approve the protocol before any subjects are enrolled
D) Public disclosure of the study and results

Answer: C

Explanation:

• FDA does NOT provide advance approval of §50.24 research protocols.
• The IRB is responsible for reviewing and approving the protocol, including documenting that all 8 criteria in §50.24(a) are met.
• FDA must be notified but does not provide preapproval.

Required under §50.24:

• ✅ Independent data monitoring committee (§50.24(a)(7)(iv))
• ✅ Community consultation before and during (§50.24(a)(7)(iii))
• ✅ Public disclosure before and after (§50.24(a)(7)(iii))
• ❌ FDA preapproval (this is NOT required)

SOCRA Exam Tip: Common misconception. FDA is notified and can object, but does not provide advance approval like for IND/IDE submissions.

Question 5: Minimal Risk Waiver (NEW 2024)

Under the 2024 revision of 21 CFR 50.22, an IRB may waive informed consent for a retrospective chart review study that involves minimal risk and uses identifiable patient data. Which finding is NOT required for this waiver?

A) Research could not practicably be carried out without the waiver
B) Research could not practicably be carried out without using identifiable data
C) Waiver will not adversely affect subjects' rights and welfare
D) Study must involve no more than 100 subjects

Answer: D

Explanation:

• There is NO limit on number of subjects for §50.22 waiver.
• The NEW 2024 provision (effective January 22, 2024) added criterion (c): "If the clinical investigation involves using identifiable private information or identifiable biospecimens, the clinical investigation could not practicably be carried out without using such information or biospecimens in an identifiable format."

Required findings for §50.22 waiver (ALL must be met):

1. ✅ Minimal risk (§50.22(a))
2. ✅ Could not practicably be done without waiver (§50.22(b))
3. ✅ If identifiable data: could not practicably be done without identifiable format (§50.22(c)) [NEW 2024]
4. ✅ Will not adversely affect rights/welfare (§50.22(d))
5. ✅ When appropriate: subjects provided info after participation (§50.22(e))

SOCRA Exam Tip: The 2024 update is testable. Know that identifiable data/biospecimens now have specific impracticability finding required.

Question 6: Pregnant Women

Research involves administering an investigational vaccine to pregnant women in their third trimester. The research presents greater than minimal risk to the fetus with no prospect of direct benefit to the fetus or woman (but may benefit society through knowledge gained). Under 45 CFR 46 Subpart B, whose consent is required?

A) Woman's consent only
B) Woman's consent + father's consent
C) Woman's consent + IRB approval is sufficient
D) This research is prohibited

Answer: B - Woman's consent + father's consent

Explanation:

• Per 45 CFR 46.204(d): When research presents >minimal risk to fetus with no prospect of direct benefit to woman or fetus, father's consent is required (unless pregnancy resulted from rape/incest, or father is unknown/unavailable/incompetent).

Decision Tree for Father's Consent:

• Risk to fetus ≤ minimal risk? → Father's consent NOT required
• Risk > minimal risk BUT direct benefit to woman or fetus? → Father's consent NOT required
• Risk > minimal risk AND no direct benefit? → Father's consent REQUIRED (unless exceptions)

Exceptions when father's consent NOT required:

• Pregnancy resulted from rape or incest
• Father is unknown
• Father is not reasonably available
• Father is incompetent

SOCRA Exam Tip: This is a high-yield question type. Focus on: >minimal risk + no benefit = father's consent required.

Question 7: Contact Information

An informed consent form provides the following contact information: "Dr. Smith (555-1234) for questions about the study." What is wrong with this contact information per 21 CFR 50.25(a)(7)?

A) Must provide 24/7 emergency contact
B) Must provide separate IRB contact for questions about subjects' rights
C) Must provide email address in addition to phone
D) Nothing is wrong

Answer: B

Explanation:

• Element 7 requires contact information for:
  1. Questions about research (provided: Dr. Smith)
  2. Questions about subjects' rights (MISSING)
  3. Research-related injury (can be same as research contact)

Minimum Requirement:

• TWO separate contacts (or one contact but clearly distinguished purposes)
• Research questions → typically PI or research coordinator
• Rights questions → typically IRB or independent institutional official

Emergency Contact:

• Not required for all studies
• Required when study involves: emergencies, 24/7 events, after-hours procedures, inpatient settings

SOCRA Exam Tip: "Two contacts" is frequently tested. Many incomplete consent forms provide only PI contact without IRB/rights contact.

Question 8: Compensation Element

Which statement about Element 6 (Compensation and Medical Treatment for Injury) is correct?

A) Required for all FDA-regulated research
B) Required only for research involving greater than minimal risk
C) Required only when compensation is actually provided
D) May be omitted if study has insurance coverage

Answer: B

Explanation:

• Per 21 CFR 50.25(a)(6): "For research involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments are available..."

Key Points:

• Only required when risk > minimal
• Must state whether compensation/treatment ARE available (even if answer is "no")
• If NO compensation/treatment available, must say so
• Cannot be omitted even if insurance exists

Examples:

Minimal Risk Study:

[Element 6 can be omitted entirely]

>Minimal Risk, No Compensation:

"If you are injured as a result of being in this study, treatment will be available but the costs may be billed to you or your insurance. No funds have been set aside to compensate you."

>Minimal Risk, Compensation Available:

"If you are injured as a direct result of being in this study, medical treatment is available and the costs will be covered by the study sponsor. You do not give up any legal rights by signing this form."

SOCRA Exam Tip: Distinguish between "when required" (>minimal risk) vs. "what to say" (whether available or not).

Question 9: Short Form Consent

When using short form written consent documentation (21 CFR 50.27(b)(2)), which of the following is correct regarding signatures?

A) Only the subject needs to sign the short form
B) The subject signs the short form; the witness signs the summary
C) The subject signs the short form; the witness signs both the short form and summary
D) Everyone signs everything

Answer: C

Explanation:

• Subject (or LAR): Signs the short form only
• Witness: Signs both the short form AND the summary
• Person obtaining consent: Signs a copy of the summary

Short Form Requirements:

• States elements of §50.25 were presented orally
• Requires witness to the oral presentation
• IRB must approve a written summary of what was said
• Witness must sign both short form and copy of summary
• Subject signs only the short form
• Person obtaining consent signs a copy of the summary

When to Use Short Form:

• Non-English speaking subjects
• Subjects with limited literacy
• Emergency situations where full written consent not feasible

SOCRA Exam Tip: Memorize who signs what. Subject = short form only. Witness = both. Common exam question.

Question 10: Voluntary Participation

Which of the following statements in an informed consent form would raise concerns about coercion or undue influence regarding voluntary participation?

A) "Participation is voluntary. You may withdraw at any time without penalty."
B) "If you decide not to participate, your regular medical care will not be affected."
C) "Participation is optional, but patients who complete the study will have priority access to Dr. Smith's clinic."
D) "You can choose not to be in this study."

Answer: C

Explanation:

• Statement C suggests participants get preferential treatment ("priority access"), which is coercive.
• Coercion = Overt threat to subject that can only be avoided by participating
• Undue Influence = Offer of excessive or inappropriate reward that subject would have difficulty refusing

Red Flags for Coercion/Undue Influence:

• Preferential treatment for participants
• Penalties for non-participants
• Implications that continued care depends on participation
• Excessive payments
• For students: grade affected
• For employees: job affected
• For patients: doctor-patient relationship affected

Acceptable Statements:

• ✅ "Your decision will not affect your medical care at this hospital."
• ✅ "Your doctor will continue to treat you whether or not you participate."
• ✅ "For students: Participation is voluntary and will not affect your grade. An alternative assignment is available."
• ✅ "For employees: Your employment status will not be affected by your decision."

SOCRA Exam Tip: Look for statements that tie benefits/penalties to participation decision. These are always problematic.

Additional Practice Questions (Brief Format)

Q11: Which element of informed consent is often overlooked but required: disclosure that FDA may inspect records?
A: Element 5 (Confidentiality) - explicitly required by §50.25(a)(5)

Q12: Can an IRB waive informed consent for greater than minimal risk research?
A: Generally NO, unless meets strict §50.24 criteria (emergency research exception)

Q13: In 45 CFR 46.406 research with children, how many parents must give permission?
A: BOTH parents (unless one deceased/unknown/incompetent/not reasonably available)

Q14: What is difference between §50.23 and §50.24?
A: §50.23 = single patient emergency USE (expanded access); §50.24 = emergency RESEARCH (prospective protocol)

Q15: Can consent form state: "The sponsor will not be held liable for any injuries"?
A: NO - this is exculpatory language, prohibited by §50.20

Q16: For prisoner research, what is special IRB requirement?
A: Majority cannot be associated with prison; at least one prisoner/representative required on IRB

Q17: Can parents waive child's assent if child objects to participation?
A: Generally NO - child's dissent must be respected (exception: intervention necessary for welfare AND only available in research)

Q18: What is "Key Information" section in informed consent?
A: Concise summary at beginning (HHS requirement per 2018 Common Rule; encouraged but not required by FDA)

Q19: Under ICH E6(R3), are electronic signatures acceptable?
A: YES - explicitly authorized when compliant with applicable regulations

Q20: When is Community Consultation required?
A: For research under §50.24 (emergency research exception) - required before AND during research

9. Quick Reference Tables

The 8 Basic Elements - At a Glance

21 CFR 50 vs. 45 CFR 46 Quick Comparison

Children Research Categories Decision Tree

START: Research involves children (<18 years)
    ↓
Q: What is the risk level?
    ↓
├── Risk ≤ MINIMAL
│   → §46.404
│   → Permission: ONE parent
│   → Assent: Required
│
├── Risk > MINIMAL, BUT offers DIRECT BENEFIT to child
│   → §46.405
│   → Permission: ONE parent
│   → Assent: Required
│
├── Risk > MINIMAL (minor increase), NO direct benefit, 
│   BUT yields GENERALIZABLE KNOWLEDGE about condition
│   → §46.406
│   → Permission: BOTH parents*
│   → Assent: Required
│
└── Doesn't fit 404/405/406 BUT reasonable opportunity 
    to understand SERIOUS PROBLEM affecting children
    → §46.407
    → Permission: BOTH parents*
    → Assent: Required
    → HHS Secretary approval required after expert panel

*Unless one parent deceased, unknown, incompetent, not available, 
or sole legal custody

Exception from Informed Consent - When Applicable?

SOCRA Exam High-Yield Topics - Study Priority

Common Consent Form Deficiencies Checklist

Use this checklist when reviewing consent forms:

Element 1 - Research Statement

• Word "research" or "study" used?
• Purpose clearly stated?
• Specific duration provided?
• All procedures described?
• Experimental procedures identified?

Element 2 - Risks

• Physical risks listed?
• Psychological risks included?
• Social risks considered?
• Pregnancy risks (if women of childbearing potential)?
• Common AND serious risks?

Element 3 - Benefits

• Realistic (not overpromised)?
• "No direct benefit" stated (if applicable)?
• Payment NOT listed as benefit?

Element 4 - Alternatives

• Standard treatments described?
• Non-participation listed as option?
• Sufficient detail for comparison?

Element 5 - Confidentiality

• FDA INSPECTION explicitly disclosed? ⚠️
• Who has access (sponsor, IRB, FDA)?
• Data protection described?
• Avoids "absolute" confidentiality promises?

Element 6 - Compensation (if >minimal risk)

• States whether compensation available?
• States whether treatment available?
• Explains what's covered?
• No exculpatory language?

Element 7 - Contact Information

• Contact for RESEARCH questions?
• Separate contact for RIGHTS questions? ⚠️
• Emergency contact (if applicable)?
• Phone numbers accurate and current?

Element 8 - Voluntary

• States "voluntary"?
• May refuse without penalty?
• May withdraw anytime without penalty?
• No loss of benefits?
• Withdrawal process explained?
• No coercive language?

Additional Elements (when applicable)

• Unforeseeable risks (b)(1)?
• Termination circumstances (b)(2)?
• Additional costs (b)(3)?
• Withdrawal consequences (b)(4)?
• New findings provision (b)(5)?
• Number of subjects (b)(6)?

Special Populations

• Children: Appropriate category (§404-407)? Assent procedures?
• Pregnant: Father consent considered? Reproductive risks?
• Prisoners: IRB composition? OHRP approval?

Final Exam Success Tips

Study Strategy

1. Master the 8 Basic Elements

   • Use mnemonic "RPRB-CCVC"
   • Know common violations for each
   • Practice identifying missing elements

2. Focus on High-Yield Topics

   • FDA inspection disclosure (Element 5)
   • When Element 6 required (>minimal risk only)
   • Two contacts minimum (Element 7)
   • Exculpatory language (always prohibited)
   • Children categories (404-407)

3. Understand Scenarios

   • SOCRA tests application, not just facts
   • Read scenarios twice carefully
   • Eliminate obviously wrong answers
   • Choose BEST answer (may be multiple partially correct)

4. Know Recent Updates

   • 2024: §50.22 expanded (identifiable data)
   • 2024: Key Information guidance
   • ICH E6(R3): eConsent provisions
   • Transition date: January 1, 2026

5. Practice, Practice, Practice

   • Use this guide's 20+ practice questions
   • Take SOCRA practice exams
   • Review missed questions thoroughly

Test-Taking Tips

✅ DO:

• Read the entire question and all options
• Look for keywords: "EXCEPT," "NOT," "BEST," "REQUIRED"
• Eliminate obviously wrong answers first
• Trust your first instinct (unless you find clear error)
• Flag difficult questions and return later

❌ DON'T:

• Rush through questions
• Assume details not explicitly stated
• Overthink simple questions
• Change answers without good reason
• Leave questions blank (no penalty for guessing)

Day Before Exam

• Review this Quick Reference section
• Quiz yourself on the 8 Basic Elements
• Review mnemonic "RPRB-CCVC"
• Scan high-yield topics list
• Get good sleep - don't cram all night

Day of Exam

• Arrive early (reduce stress)
• Bring required identification
• Use scratch paper for notes/calculations
• Manage your time (100 questions in 2.5 hours = ~1.5 min/question)
• Review flagged questions if time permits

Resources for Further Study

Primary Regulatory Sources

21 CFR Part 50 - Protection of Human Subjects
https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-50

45 CFR Part 46 - Protection of Human Subjects
https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-A/part-46

ICH E6(R3) - Good Clinical Practice
https://www.ich.org (search for E6(R3))

FDA Guidance Documents

Key Information and Facilitating Understanding in Informed Consent
https://www.fda.gov/regulatory-information/search-fda-guidance-documents

Questions and Answers on Informed Consent Elements (21 CFR 50.25(c))
https://www.fda.gov/regulatory-information/search-fda-guidance-documents

OHRP Resources

OHRP Informed Consent FAQs
https://www.hhs.gov/ohrp/regulations-and-policy/guidance/faq/informed-consent/index.html

OHRP Subpart Guidance (B, C, D)
https://www.hhs.gov/ohrp/regulations-and-policy/guidance/

SOCRA Resources

SOCRA Certification Exam Outline
https://www.socra.org/certification/ccrp-certification-exam/exam-outline/

SOCRA Preparation Resources
https://www.socra.org/certification/ccrp-certification-exam/preparation-resources/

21 CFR PART 50 QUICK REFERENCE GUIDE

SOCRA CCRP Exam - Essential Facts on One Page

🔥 THE 8 BASIC ELEMENTS (§50.25(a)) - MEMORIZE THIS!

Mnemonic: "RPRB-CCVC"

⚠️ MOST TESTED TOPICS

Element 5: FDA Inspection 🔥🔥🔥

MUST explicitly state: "The Food and Drug Administration (FDA) may inspect study records."

• ❌ NOT sufficient: "Sponsor may review records" or "IRB may inspect"
• ✅ REQUIRED: Explicit FDA mention

Element 6: Compensation 🔥🔥🔥

Required ONLY for >minimal risk research

• Minimal risk study? → Can omit Element 6

• Minimal risk study? → MUST include (even if "none available")

Element 7: Two Contacts Minimum 🔥🔥

• Contact #1: Questions about RESEARCH (PI/coordinator)
• Contact #2: Questions about RIGHTS (IRB)
• Cannot be same person serving both roles without clarification

🚫 EXCULPATORY LANGUAGE - ALWAYS PROHIBITED

NEVER allowed:

• "You give up your right to sue..."
• "You waive all claims..."
• "Institution not responsible for injuries..."
• "By signing, you release investigators..."

Always acceptable:

• "Signing does not waive your legal rights."
• "You do not give up legal rights by participating."

👶 CHILDREN RESEARCH - 45 CFR 46 Subpart D

*Unless one parent: deceased, unknown, incompetent, unavailable

Quick Decision:

• Direct benefit to child? → 1 parent OK
• No benefit, >minimal risk? → BOTH parents required

🤰 PREGNANT WOMEN - 45 CFR 46 Subpart B

Father's Consent Required When:

• Risk to fetus >minimal AND
• NO direct benefit to woman or fetus

Exceptions (father NOT needed):

• Pregnancy from rape/incest
• Father unknown/unavailable/incompetent

⚖️ EXCEPTIONS FROM INFORMED CONSENT

Emergency Research Exception (§50.24)

8 Criteria - ALL required:

1. Life-threatening situation
2. Available treatments unproven/unsatisfactory
3. Consent not feasible (medical condition + time + can't ID prospectively)
4. Prospect of direct benefit to subjects
5. Could not practicably do without waiver
6. Therapeutic window defined + attempt LAR contact
7. Consent procedures for when feasible
8. Community consultation + public disclosure + data monitoring + family contact

Common Misconception: ❌ FDA does NOT pre-approve §50.24 protocols; IRB approves

Waiver for Minimal Risk (§50.22) - NEW 2024

All required:

1. ≤ Minimal risk
2. Impracticable without waiver
3. [NEW] If identifiable data: impracticable without ID format
4. Won't adversely affect rights/welfare
5. Info provided after (when appropriate)

📋 SHORT FORM CONSENT (§50.27(b)(2))

Who Signs What:

• Subject/LAR: Signs SHORT FORM only
• Witness: Signs SHORT FORM + SUMMARY (both)
• Person obtaining consent: Signs SUMMARY

Requirements:

• Short form states elements presented orally
• Witness to oral presentation required
• IRB approves written summary
• Used for: non-English speakers, limited literacy

🆕 ICH E6(R3) KEY UPDATES (Effective 2026)

eConsent Provisions:

• ✅ Electronic signatures authorized
• ✅ Multimedia tools (videos, animations)
• ✅ Remote consent via video conference
• ✅ Interactive comprehension checks
• ✅ Enhanced accessibility requirements

Risk-Proportionate Approach:

• Consent complexity matches study risk
• Simplified procedures for low-risk studies
• Flexible tailoring of elements

📊 21 CFR 50 vs. 45 CFR 46

⏱️ COMMON EXAM QUESTION TYPES

1. "What is MISSING?"

Present incomplete consent → identify missing element Strategy: Check all 8 elements systematically

2. Exculpatory Language

Present problematic language → identify as prohibited Strategy: Look for "waive rights," "release liability," "not responsible"

3. Vulnerable Populations

Children/pregnant/prisoner scenario → what consent required? Strategy: Use decision trees (§404-407 for children)

4. Exception Criteria

Emergency research → what's required/not required? Strategy: Know §50.24 doesn't require FDA preapproval

5. Documentation

Short form consent → who signs what? Strategy: Subject=short form; Witness=both; Obtainer=summary

✅ PRE-EXAM CHECKLIST

Day Before:

• Review 8 Basic Elements + mnemonic
• Review Element 5 (FDA inspection)
• Review Element 6 (when required)
• Review Element 7 (two contacts)
• Review exculpatory language examples
• Review children categories (§404-407)
• Review §50.24 criteria (emergency research)

Exam Day Strategy:

• Read entire question before answering
• Look for keywords: "EXCEPT," "NOT," "BEST"
• Eliminate wrong answers first
• Flag difficult questions, return later
• Don't change answers without good reason

🎯 HIGHEST-YIELD FACTS

1. FDA INSPECTION must be explicitly disclosed in Element 5
2. Element 6 required ONLY for >minimal risk
3. TWO CONTACTS minimum: research + rights questions
4. EXCULPATORY LANGUAGE always prohibited (easy points!)
5. §50.24 IRB approves (not FDA pre-approval)
6. §406/§407 children research requires BOTH parents
7. SHORT FORM: Subject signs short form; witness signs both
8. FATHER'S CONSENT: Required when >min risk + no benefit to woman/fetus
9. NEW 2024: §50.22 waiver expanded for identifiable data
10. E6(R3): eConsent explicitly authorized (2026+)

📞 EMERGENCY CONTACTS FOR QUESTIONS

Regulations:

• 21 CFR 50: https://ecfr.gov
• 45 CFR 46: https://ecfr.gov
• ICH E6(R3): https://ich.org

Guidance:

• FDA Guidance: https://www.fda.gov/regulatory-information
• OHRP Guidance: https://www.hhs.gov/ohrp

Document Version History

Version 1.0 - October 2025
Reflects 2024 regulatory updates and ICH E6(R3) for January 2026 exam transition

• Comprehensive guide for SOCRA CCRP Exam
• Reflects 2024 regulatory updates
• Includes ICH E6(R3) content
• 20+ practice questions with detailed explanations
• Prepared for January 2026 exam transition