GC159 Research Ethics (notes)
Research ethics is the framework of principles and regulatory guidelines—including informed consent, beneficence, non-maleficence, justice, and institutional review—that govern the conduct of biomedical and clinical research involving human subjects.
Research Ethics and All That Jazz
Lecture Map
Clinical research is the engine that brings new drugs and devices from the lab bench to the bedside. However, because it inherently involves using humans as experimental subjects, it demands a rigorous ethical and regulatory framework. This lecture lays out why those frameworks exist (historical atrocities), what the frameworks are (GCP, ICH, IRB/Ethics Committees, Declaration of Helsinki, Nuremberg Code), how they operate in practice (the 10 GCP principles, the 4 phases of clinical trials, informed consent), and where things go wrong (FDA audit findings). Every clinical student will eventually encounter research — as a reader, a participant, or an investigator — and ethics questions appear reliably in summative exams. [1]
By the end of the lecture the student should be able to:
- Define sponsor, investigator, IRB and GCP
- List the 10 principles of GCP
- Determine how HKU/HA Faculty of Medicine applies Research Ethics
- List 3 problems identified with Clinical Trials when audited by FDA [1]
Research ethics is examined as:
- SAQ/Minicase: Define terms (sponsor, investigator, IRB, GCP); list GCP principles; identify ethical violations in a scenario
- MCQ: Identifying phases of clinical trials; recognising consent issues
- Viva/OSCE: Discussing informed consent, confidentiality in research, ethical violations in a clinical scenario
- Related GC lectures on Confidentiality (GC 174) and Ethics in Psychiatry (GC 173) share overlapping frameworks (Nuremberg Code, Declaration of Helsinki, IRB) [1][2]
Core Concepts and Definitions
Clinical research is conducted to evaluate the safety and efficacy of new pharmaceutical agents, or medical devices, in anticipation of widespread use by the general public. [1]
Think of it from first principles: before any drug can be sold to millions of people, someone must prove that (a) it is safe — it won't kill or harm at an unacceptable rate, and (b) it is efficacious — it actually does what it claims. This cannot be fully determined from animal studies or lab experiments alone because human biology is different. So we need controlled experiments in humans — clinical trials.
But humans are not lab rats. They have rights, autonomy, and dignity. This fundamental tension — the need for human experimentation vs. the obligation to protect human subjects — is the entire reason research ethics exists.
| Term | Definition | Why It Matters |
|---|---|---|
| Sponsor | The company that normally initiates the clinical trial | The sponsor funds, designs, and often drives the research agenda. They have financial incentives — this is why independent oversight is critical. [1] |
| Investigator | The person who carries out the clinical trial | The investigator has dual obligations: to the sponsor (deliver results) and to the patient-subject (protect their welfare). Understanding this tension is key to understanding ethical violations. [1] |
| IRB (Institutional Review Board) / Ethics Committee | A committee at each institution that reviews clinical trials to ensure ethical standards are met | Introduced by the Declaration of Helsinki (1964). The IRB provides independent, external oversight — the investigator cannot be the sole judge of whether their own study is ethical. [1] |
| GCP (Good Clinical Practice) | The roles and operating procedures that set standards for all aspects of clinical research, with two goals: (1) protection of human subjects, and (2) maintenance of highest standards of scientific practice | GCP is the rulebook. It is NOT a product of any single regulatory agency like the FDA — it evolved from historical ethical codes and international consensus. [1] |
High Yield Exam Definition
"Any research using human subjects demands the highest level of scientific rigor and ethical conduct. The roles and operating procedures is known as Good Clinical Practice (GCP)." GCP has a two-fold goal: (1) protection of human subjects and (2) maintenance of the highest standards of scientific practice. Know both goals — exam answers that only mention one will lose marks. [1]
GCP guidelines have evolved over a period of time and are NOT the product of an agency such as the Food and Drug Administration (FDA) that regulates or approves medications for use. [1]
This is a critical conceptual point and a common exam trap. Students often assume GCP = FDA regulation. It's not. GCP is a set of ethical and scientific quality standards that evolved from historical events and international consensus. The FDA uses GCP, but GCP is bigger than the FDA.
Timeline of Key Documents
| Year | Document | Key Contribution |
|---|---|---|
| 1947 | Nuremberg Code | Emerged from WWII war crimes trials. Established that human subjects must not be used in clinical trials without proper welfare considerations. First codification of voluntary informed consent as an absolute requirement. [1][2] |
| 1964 | Declaration of Helsinki | Introduced the concept that each institution should have an ethics committee or IRB to review clinical trials. This shifted ethics from individual investigator conscience to institutional oversight. A copy is kept in the HKU Faculty Seminar Room. [1] |
| Ongoing | ICH-GCP Guidelines | International Conference on Harmonization issued guidelines to standardize GCP worldwide, because many clinical studies are now international multi-centre trials. There is a pressing need to obtain and validate comparable data quality across national borders. [1] |
Why ICH Matters
Modern drug trials are not done in one hospital in one country. A single Phase III trial might involve 200 sites across 30 countries. Without harmonised standards, data from site A in Tokyo cannot be meaningfully compared with data from site B in London. ICH-GCP solves this by creating a single rulebook that meets the regulatory requirements of all major governments. [1]
GCP principles should be used in all 4 stages of Clinical Trials. [1]
| Phase | Name | Key Question | Details |
|---|---|---|---|
| Phase I | Clinical Pharmacology | "Is it safe in normals?" | Tested in a small number of healthy volunteers (typically 20-80). Primary goal is to determine pharmacokinetics, pharmacodynamics, safe dosage range, and side effects. NOT looking for efficacy yet. [1] |
| Phase II | Controlled Clinical Trials | "Does it work?" | Tested in patients who have the target disease (typically 100-300). Begins to assess efficacy and optimal dosing. Usually randomised controlled trials. [1] |
| Phase III | Expanded Clinical Trials | "Is it better?" | Large-scale trials (typically 1000-3000+ patients) comparing the new drug against the current standard of care or placebo. This is the definitive evidence needed for regulatory approval. [1] |
| Phase IV | Post-marketing Studies | "Will it have any long-term results?" | Conducted after the drug is approved and on the market. Monitors for rare or long-term adverse effects in the general population. This is how problems like the COX-2 inhibitor cardiovascular risk were discovered. [1] |
Exam Trap
Students commonly confuse Phase I and Phase II. Remember: Phase I = safety in healthy volunteers. Phase II = efficacy in patients with the disease. The mnemonic: Phase 1 = 1st priority is Safety; Phase 2 = does it do what it's supposed to do?
Why do we need all 4 phases? Think of it as a funnel. Phase I catches drugs that are too toxic. Phase II catches drugs that don't work. Phase III catches drugs that work but aren't better than what we already have. Phase IV catches rare problems that only emerge when millions of people use the drug. Each phase has progressively more subjects and progressively more real-world conditions.
This is one of the highest-yield lists in the lecture. The lecture provides a mnemonic-style summary in the left column and the full principle in the right column. Know both. [1]
There are 10 basic principles of GCP:
| # | Short Summary | Full Principle | Why It Matters |
|---|---|---|---|
| 1 | The study is well thought out | The sponsor's overall clinical development plan must be well crafted | A poorly designed development program wastes resources and exposes subjects to risk without proportionate benefit. [1] |
| 2 | And scientific | Each study must be designed in accordance with sound scientific principles | Bad science = bad ethics. If a study is methodologically flawed, it cannot produce valid results, meaning subjects were exposed to risk for nothing. [1] |
| 3 | The patients' rights are protected | The rights and safety of subjects must be protected by external review and approval of proposed procedures | This is the IRB/Ethics Committee role. External review is key — you cannot mark your own homework. [1] |
| 4 | And they have given consent | Consent to participate in the study must be informed and freely given | "Informed" = the subject understands what they're agreeing to. "Freely given" = no coercion. This is the legacy of Nuremberg. [1] |
| 5 | The study adheres to guidelines | The study must be executed in conformance with accepted regulatory guidelines | Following the protocol protects data integrity and subject safety. [1] |
| 6 | And is monitored | The study must be monitored by the sponsor or its delegate for compliance with the guidelines | Trust but verify. The sponsor has a duty to check that investigators are actually following the rules. [1] |
| 7 | The data arising is accurate | The data must be complete and accurately reflect information in source documents | Fabricated or inaccurate data can lead to approval of dangerous or ineffective drugs. [1] |
| 8 | And accounted for | There must be complete accountability for test articles, their storage and final disposition | Drug accountability means knowing exactly how many doses were dispensed, used, returned, and destroyed. Prevents diversion and ensures dosing accuracy. [1] |
| 9 | And kept in a proper place | Proper record keeping and record retention practices must be followed | Records must be preserved for audit trails. If you can't prove something happened correctly, you can't claim it did. [1] |
| 10 | And that there is a plan of quality assurance | A plan of quality assurance must be in place and implemented throughout the study | QA is not an afterthought — it must be planned from the start and implemented throughout (not just at the end). [1] |
Memory Aid for 10 GCP Principles
Think of them in logical groups:
- Design (1-2): Well-crafted plan + sound science
- Protection (3-4): External review + informed consent
- Execution (5-6): Follow guidelines + monitor compliance
- Data (7-8-9): Accurate data + drug accountability + record keeping
- Quality (10): QA throughout
The IRB / Ethics Committee
In 1964 the Declaration of Helsinki introduced the concept that each institution should have an ethics committee or institutional review board (IRB) that should review clinical trials that take place in a hospital or institution. [1]
Before Helsinki, research ethics depended on the individual conscience of the investigator. The problem? Investigators have inherent conflicts of interest — career advancement, funding, publications. Helsinki's genius was introducing institutional oversight — an independent body that reviews protocols before subjects are enrolled.
The ethics committee is NOT involved with research involving animals; that is done by another committee (CULATR). [1]
CULATR = Committee on the Use of Live Animals in Teaching and Research. This is a separate body. If an exam question asks about animal research ethics oversight, the answer is CULATR, not the IRB.
There is a combined HKU HA ethics committee (or institutional review board) that comprises members from the Faculty, a non-faculty member and a representative from the Hospital Authority. The committee reviews over 150 protocols a year in circulation as well as face to face meetings. The commitment is to adhere to the Principles of Helsinki and also to the ICH-GCP guidelines. [1]
| Feature | Detail |
|---|---|
| Composition | Faculty members + non-faculty member + Hospital Authority representative |
| Volume | Reviews > 150 protocols/year |
| Standards | Declaration of Helsinki + ICH-GCP guidelines |
| Method | Circulation review + face-to-face meetings |
Why a non-faculty member? To provide a lay perspective and prevent institutional groupthink. The non-faculty member represents the public interest — they ensure that the committee doesn't become an insular club of researchers rubber-stamping each other's protocols.
Why an HA representative? Because clinical trials at HKU often involve HA hospital patients. The HA has a duty to protect its patients regardless of whether the research is academically sound.
The investigator must ensure that a proper informed consent is signed. [1]
Informed Consent in Research
The individual has been given all the information a rational person needs to assess the personal risks, requirements, and rewards of participation in a research study. [1]
Break this down:
- "All the information" — not a selective subset that makes the study sound appealing
- "A rational person" — the standard is not what a medical professional would understand, but what a reasonable layperson would need
- "Personal risks" — side effects, potential harm, inconvenience
- "Requirements" — what participation involves (visits, blood draws, lifestyle changes)
- "Rewards" — potential benefits (which may be none for the individual subject)
In any procedure that you are performing on a patient informed consent needs to be given. This should also be borne in mind when you are doing minor procedures. [1]
This is a practical clinical point. Even as a medical student performing a venepuncture, you need to explain what you're doing and get verbal consent. In research, this is formalised with a written consent form, but the principle is the same.
Obtain informed consent (writing or oral) – an ongoing not singular process. Enumerate how to manage privacy and confidentiality. Data reporting, handling and disposal. [2]
Key Concept: Consent is Ongoing
Informed consent is an ongoing process, not a singular event. A patient signing a form at enrolment does not mean consent is permanently granted. Subjects must be kept informed of new findings, and consent must be reconfirmed if the study changes significantly. [2]
Routine FDA audit findings:
- Inadequate consent form: 56%
- Inadequate and inaccurate records: 23%
- Inaccurate drug accountability: 22%
- Failure to adhere to protocol: 9%
- Failure to keep IRB informed of changes: 9% [1]
| Violation | Frequency | Why It's a Problem |
|---|---|---|
| Inadequate consent form | 56% | The single most common violation. Forms may be missing required elements, use jargon patients can't understand, or fail to disclose all risks. This directly violates GCP Principle 4. [1] |
| Inadequate and inaccurate records | 23% | If you can't trust the records, you can't trust the data. Violates GCP Principles 7 and 9. [1] |
| Inaccurate drug accountability | 22% | Not knowing where the study drug went means you don't know if subjects received the correct dose — or if drug was diverted. Violates GCP Principle 8. [1] |
| Failure to adhere to protocol | 9% | Protocol deviations compromise data integrity and may expose subjects to unanticipated risks. Violates GCP Principle 5. [1] |
| Failure to keep IRB informed of changes | 9% | The IRB can only protect subjects if it knows what's actually happening. Failing to report changes undermines the entire oversight system. Violates GCP Principle 3. [1] |
Exam High Yield
The most common FDA audit finding is inadequate consent form (56%). This is the single most commonly tested fact from this lecture. The top 3 problems are consent (56%), records (23%), and drug accountability (22%). Be able to list at least 3. [1]
Case in point: "Doctored files" (to be shown during lecture). List the following areas where Dr Poisson violated GCP principles. [1]
This refers to the famous case of Dr. Roger Poisson of Montreal, who was found to have falsified data in breast cancer clinical trials (NSABP trials). He enrolled patients who did not meet eligibility criteria, fabricated laboratory results to make them appear eligible, and altered records to conceal the fraud.
GCP Principles violated by Dr. Poisson:
- Principle 2 (sound scientific principles) — Enrolling ineligible patients corrupts the science
- Principle 4 (informed consent) — Patients consented to a study they may not have actually qualified for; the consent was therefore based on false premises
- Principle 5 (adherence to regulatory guidelines/protocol) — Deliberately deviated from inclusion/exclusion criteria
- Principle 7 (data accuracy) — Fabricated lab results and altered records
- Principle 9 (proper record keeping) — Records were falsified, not properly maintained
- Principle 10 (quality assurance) — The QA system failed to catch the fraud for years
This case illustrates why external monitoring (Principle 6) and institutional oversight (Principle 3) are essential — relying on investigator honesty alone is insufficient.
Confidentiality in Research: The Nuremberg Code, Declaration of Helsinki, Personal Data (Privacy) Ordinance, IRB, LKS Faculty of Medicine Research Ethics. [2]
Main ethical issues in human subject research: Obtain informed consent (writing or oral) – an ongoing not singular process. Enumerate how to manage privacy and confidentiality. Data reporting, handling and disposal. [2]
Research generates large amounts of personal health data. Confidentiality obligations in research include:
- Anonymisation/de-identification of data wherever possible
- Secure storage with restricted access
- Clear data disposal protocols after the study ends
- Compliance with the Personal Data (Privacy) Ordinance (PDPO) in Hong Kong
- IRB oversight of data handling plans
From GC 174 and other ethics lectures, the broader ethical framework that underpins research ethics includes [2][3]:
| Framework | Application to Research Ethics |
|---|---|
| Principlism (Beauchamp & Childress) | Autonomy → informed consent; Beneficence → potential benefit to society/subjects; Non-maleficence → minimise harm to subjects; Justice → fair subject selection, equitable distribution of research benefits and burdens |
| Nuremberg Code | Voluntary consent is absolutely essential |
| Declaration of Helsinki | IRB review, ongoing consent, duty to publish results, best proven treatment as comparator |
| ICH-GCP | 10 principles as detailed above |
| PDPO | Hong Kong law governing handling of personal data — applies to research data |
For the Medical Student / Junior Doctor
- If asked to recruit patients for a study: Ensure IRB approval exists, consent form is approved, you understand the protocol, and you can explain risks/benefits in plain language
- If performing a procedure as part of research: Separate research consent from clinical consent
- If you notice protocol violations: Report to the IRB — you have an ethical duty to do so
- If a patient in a trial develops an adverse event: Report as per protocol, and ensure the IRB is informed (serious adverse events require expedited reporting)
- If a patient wants to withdraw from a trial: They have an absolute right to do so at any time, without penalty to their clinical care
Exam Intelligence
| Trap | Correct Understanding |
|---|---|
| "GCP was created by the FDA" | GCP guidelines are NOT the product of the FDA. They evolved from the Nuremberg Code (1947), Declaration of Helsinki (1964), and ICH consensus. The FDA uses GCP but did not create it. [1] |
| "Phase I trials test efficacy" | Phase I tests safety in healthy volunteers. Efficacy testing begins in Phase II. [1] |
| "The IRB reviews animal research" | The ethics committee is NOT involved with research involving animals; that is done by another committee (CULATR). [1] |
| "Informed consent is a one-time event" | Consent is an ongoing process, not singular. Must be maintained throughout the study. [2] |
| "The most common FDA audit problem is protocol violation" | The most common finding is inadequate consent form (56%). [1] |
| Confusing sponsor and investigator | Sponsor = initiates/funds. Investigator = carries out. They are different parties with different responsibilities. [1] |
| Concept A | Concept B | Key Difference |
|---|---|---|
| Nuremberg Code (1947) | Declaration of Helsinki (1964) | Nuremberg = first codification of voluntary consent; Helsinki = added IRB/ethics committee concept |
| IRB | CULATR | IRB = human subjects; CULATR = animal subjects |
| GCP | GMP (Good Manufacturing Practice) | GCP = clinical trials; GMP = drug manufacturing |
| Phase II | Phase III | Phase II = does it work (efficacy); Phase III = is it better than existing treatment (comparative) |
After reviewing all indexed past paper files, no questions directly and specifically testing the GC 159 Research Ethics lecture content (definitions of sponsor/investigator/IRB/GCP, 10 GCP principles, 4 clinical trial phases, FDA audit findings) were found verbatim in the indexed past paper extracts.
However, several past paper questions test related ethical frameworks that overlap with this lecture:
2019 Fourth Summative SAQ Q12 [4]:
Mrs. Chan is an 87-year-old lady with early dementia... (a) With reference to ethical principles, list two arguments for and two arguments against commencing resuscitation. (b) What would you do? Justify your answer.
- Relevance: Tests principlism (autonomy, beneficence, non-maleficence, justice) which underpins research ethics
- Answer: Arguments for CPR: beneficence (preserving life), family wishes (some weight). Arguments against: autonomy (patient expressed DNACPR wish), non-maleficence (futile intervention causes suffering). Action: Perform CPR (no valid DNACPR form in records — legally you must resuscitate), then discuss DNACPR formally with team and family afterwards.
2020 Fourth Summative Minicases Q8-10 [5]:
Which ethical principle is violated and why? List three points of how you would respond to the daughter's request? With reference to principlism, list three possible factors that may contribute to non-disclosure of diagnosis.
- Relevance: Tests principlism framework applied to clinical ethics — same framework applies to research ethics
2022 Fourth Summative SAQ Q10 [6]:
Give four ethical objections to the use of donor sperm.
- Relevance: Tests ethical reasoning skills that parallel research ethics analysis
2021 Fourth Summative Minicase Q16 [7]:
Name key issues in the system development [AI for precision medicine in lung cancer] to gain the public confidence and trust.
- Relevance: Tests ethical frameworks around data handling, consent, and trust — all central to research ethics
High Yield Summary
Research Ethics — What You Must Know for the Exam:
-
Definitions: Sponsor (initiates/funds), Investigator (carries out), IRB/Ethics Committee (external review body introduced by Helsinki 1964), GCP (standards for ethical and scientific conduct of clinical research — NOT an FDA product)
-
GCP has two goals: Protection of human subjects AND maintenance of highest scientific standards
-
Historical evolution: Nuremberg Code 1947 → Declaration of Helsinki 1964 → ICH-GCP (international harmonization)
-
4 Phases of Clinical Trials: Phase I (safety in normals), Phase II (does it work), Phase III (is it better), Phase IV (post-marketing long-term surveillance)
-
10 GCP Principles in groups: Design (well-crafted + scientific) → Protection (external review + consent) → Execution (follow guidelines + monitor) → Data (accurate + accountable + proper records) → Quality (QA throughout)
-
HKU/HA Ethics Committee: Combined body with faculty + non-faculty + HA representative, reviews > 150 protocols/year, adheres to Helsinki + ICH-GCP
-
Informed consent: All information a rational person needs to assess personal risks, requirements, and rewards — ongoing process, not singular
-
Top FDA audit violations: Consent form (56%) > > Records (23%) ≈ Drug accountability (22%) > Protocol adherence (9%) = Failure to inform IRB (9%)
-
IRB does NOT cover animal research — that is CULATR
-
The "Doctored Files" case (Dr. Poisson): Fabricated data, enrolled ineligible patients — violated principles 2, 4, 5, 7, 9, 10
Active Recall - Research Ethics
[1] Lecture slides: GC 159. Research Ethics (Notes).pdf (pp. 1-3) [2] Lecture slides: GC 174. Confidentiality Balancing public vs private interests.pdf (pp. 10, 27) [3] Lecture slides: GC 173. Why should I be locked up Ethics in psychiatry, Consent and Refusal in Treatment.pdf [4] Past papers: 2019 Fourth Summative SAQ.pdf (Q12, p.6) [5] Past papers: 2020 Fourth Summative Minicases.pdf (Q8-10, p.22) [6] Past papers: 2022 Fourth Summative SAQ.pdf (Q10, p.11) [7] Past papers: 2021 Fourth Summative Minicase.pdf (Q16, p.20)
GC158 Point-of-care Testing (POCT)
Point-of-care testing is diagnostic testing performed at or near the site of patient care, outside the central laboratory, to provide rapid results that facilitate immediate clinical decision-making.
GC160 The Woman Needs That Drug Oral Contraceptives Drugs Affecting Uterine Motility
Oral contraceptives are estrogen-progestin or progestin-only formulations that prevent ovulation, alter the endometrium, and thicken cervical mucus, while uterine motility drugs such as oxytocin, ergot alkaloids, prostaglandins, and tocolytics either stimulate or inhibit uterine contractions to manage labor, postpartum hemorrhage, or preterm labor.