DoH Declaration of Helsinki

Question 1

PREAMBLE

The ____ (WMA) has developed the ____ as a statement of ____ principles for ____, including research on identifiable human material and data.

The Declaration is intended to be read as ____ and each of its constituent paragraphs should be applied with consideration of all other relevant paragraphs.

Answer 1

The World Medical Association (WMA) has developed the Declaration of Helsinki as a statement of ethical principles for medical research involving human subjects, including research on identifiable human material and data.

The Declaration is intended to be read as a whole and each of its constituent paragraphs should be applied with consideration of all other relevant paragraphs.

Question 2

PREAMBLE

Consistent with the mandate of the WMA, the Declaration is addressed primarily to ____. The WMA encourages others who are involved in ____ to adopt these principles.

Answer 2

Consistent with the mandate of the WMA, the Declaration is addressed primarily to physicians. The WMA encourages others who are involved in medical research involving human subjects to adopt these principles.

Question 3

GENERAL PRINCIPLES

The Declaration of Geneva of the WMA binds the physician with the words, “____ will be my first consideration,” and the International Code of Medical Ethics declares that, “A physician shall ____ when providing medical care.”

Answer 3

The Declaration of Geneva of the WMA binds the physician with the words, “The health of my patient will be my first consideration,” and the International Code of Medical Ethics declares that, “A physician shall act in the patient’s best interest when providing medical care.”

Question 4

GENERAL PRINCIPLES

It is the duty of the physician to promote and safeguard the ____, ____ and ____ of patients, including those who are involved in medical research. The physician’s ____ and ____ are dedicated to the fulfillment of this duty.

Answer 4

It is the duty of the physician to promote and safeguard the health, well-being and rights of patients, including those who are involved in medical research. The physician’s knowledge and conscience are dedicated to the fulfillment of this duty.

Question 5

GENERAL PRINCIPLES

Medical progress is based on research that ____ must include studies involving ____.

Answer 5

Medical progress is based on research that ultimately must include studies involving human subjects.

Question 6

GENERAL PRINCIPLES

The primary purpose of medical research involving human subjects is to understand the ____,
____ and ____ of diseases and improve ____, ____ and ____ interventions (methods, procedures and treatments).

Answer 6

The primary purpose of medical research involving human subjects is to understand the causes, development and effects of diseases and improve preventive, diagnostic and therapeutic interventions (methods, procedures and treatments).

Question 7

GENERAL PRINCIPLES

Medical research is subject to ____ standards that promote and ensure ____ for all human subjects and protect their ____ and ____.

Answer 7

Medical research is subject to ethical standards that promote and ensure respect for all human subjects and protect their health and rights.

Question 8

GENERAL PRINCIPLES

While the ____ purpose of medical research is to generate new knowledge, this goal can ____ take precedence over the ____ and ____ of individual research subjects.

Answer 8

While the primary purpose of medical research is to generate new knowledge, this goal can never take precedence over the rights and interests of individual research subjects.

Question 9

GENERAL PRINCIPLES

It is the duty of physicians who are involved in medical research to protect the ____, ____, ____, ____, ____, ____, and ____ of research subjects.

Answer 9

It is the duty of physicians who are involved in medical research to protect the life, health, dignity, integrity, right to self-determination, privacy, and confidentiality of personal information of research subjects.

Question 10

GENERAL PRINCIPLES

The responsibility for the protection of research subjects must ____ rest with the physician or other health care professionals and ____ with the research subjects, even though they have ____.

Answer 10

The responsibility for the protection of research subjects must always rest with the physician or other health care professionals and never with the research subjects, even though they have given consent.

Question 11

GENERAL PRINCIPLES

Even the best proven interventions must be evaluated continually through research for their ____, ____, ____, ____ and ____.

Answer 11

Even the best proven interventions must be evaluated continually through research for their safety, effectiveness, effficiency, accessibility and quality.

Question 12

GENERAL PRINCIPLES

Physicians must consider the ____, ____ and ____ norms and standards for research involving human subjects in their own countries as well as applicable ____ norms and standards.

Answer 12

Physicians must consider the ethical, legal and regulatory norms and standards for research involving human subjects in their own countries as well as applicable international norms and standards.

Question 13

GENERAL PRINCIPLES

No ____ or ____ ethical, legal or regulatory requirement should reduce or eliminate any of the protections for research subjects set forth in this Declaration.

Answer 13

No national or international ethical, legal or regulatory requirement should reduce or eliminate any of the protections for research subjects set forth in this Declaration.

Question 14

GENERAL PRINCIPLES

Medical research should be conducted in a manner that minimizes possible harm to the ____.

Answer 14

Medical research should be conducted in a manner that minimises possible harm to the environment.

Question 15

GENERAL PRINCIPLES

Medical research involving human subjects must be conducted only by individuals with the appropriate ____ and ____ education, training and qualifications. Research on patients or healthy volunteers requires the supervision of a competent and appropriately qualified ____ or other health care professional.

Answer 15

Medical research involving human subjects must be conducted only by individuals with the appropriate ethics and scientific education, training and qualifications. Research on patients or healthy volunteers requires the supervision of a competent and appropriately qualified physician or other health care professional.

Question 16

GENERAL PRINCIPLES

Groups that are ____ in medical research should be provided appropriate access to participation in research.

Answer 16

Groups that are underrepresented in medical research should be provided appropriate access to participation in research.

Question 17

GENERAL PRINCIPLES

Physicians who combine medical research with medical care should involve their patients in research only to the extent that this is ____ by its potential preventive, diagnostic or therapeutic value and if the physician has good reason to believe that participation in the research study will ____ affect the health of the patients who serve as research subjects.

Answer 17

Physicians who combine medical research with medical care should involve their patients in research only to the extent that this is justified by its potential preventive, diagnostic or therapeutic value and if the physician has good reason to believe that participation in the research study will not adversely affect the health of the patients who serve as research subjects.

Question 18

GENERAL PRINCIPLES

Appropriate ____ and ____ for subjects who are harmed as a result of participating in research must be ensured.

Answer 18

Appropriate compensation and treatment for subjects who are harmed as a result of participating in research must be ensured.

Question 19

GENERAL PRINCIPLES

In medical practice and in medical research, most interventions involve ____. Medical research involving human subjects may only be conducted if the importance of the objective outweighs the ____ to the research subjects.

Answer 19

In medical practice and in medical research, most interventions involve risks and burdens. Medical research involving human subjects may only be conducted if the importance of the objective outweighs the risks and burdens to the research subjects.

Question 20

Risks, Burdens and Benefits

All medical research involving human subjects must be preceded by careful assessment of predictable ____ to the individuals and groups involved in the research in comparison with foreseeable ____ to them and to other individuals or groups affected by the condition under investigation.

Answer 20

All medical research involving human subjects must be preceded by careful assessment of predictable risks and burdens to the individuals and groups involved in the research in comparison with foreseeable benefits to them and to other individuals or groups affected by the condition under investigation.

Question 21

Risks, Burdens and Benefits

Measures to ____ the risks must be implemented. The risks must be ____ monitored, assessed and documented by the researcher.

Answer 21

Measures to minimise the risks must be implemented. The risks must be continuously monitored, assessed and documented by the researcher.

Question 22

Risks, Burdens and Benefits

Physicians may not be involved in a research study involving human subjects unless they are confident that the risks have been adequately ____ and can be satisfactorily ____.

Answer 22

Physicians may not be involved in a research study involving human subjects unless they are confident that the risks have been adequately assessed and can be satisfactorily managed.

Question 23

Risks, Burdens and Benefits

When the risks are found to ____ the potential benefits or when there is conclusive ____, physicians must assess whether to continue, modify or immediately stop the study.

Answer 23

When the risks are found to outweigh the potential benefits or when there is conclusive proof of definitive outcomes, physicians must assess whether to continue, modify or immediately stop the study.

Question 24

Vulnerable Groups and Individuals

Some groups and individuals are particularly ____ and may have an ____ likelihood of being wronged or of incurring additional harm.

Answer 24

Some groups and individuals are particularly vulnerable and may have an increased likelihood of being wronged or of incurring additional harm.

Question 25

# Vulnerable Groups and Individuals All vulnerable groups and individuals should receive ___ considered protection.

Answer 25

All vulnerable groups and individuals should receive specifically considered protection.

Question 26

# Vulnerable Groups and Individuals Medical research with a vulnerable group is only justified if the research is responsive to the ____ of this group and the research cannot be carried out in a ____ group. In addition, this group should stand to ____ from the knowledge, practices or interventions that result from the research.

Answer 26

Medical research with a vulnerable group is only justified if the research is responsive to the **health needs or priorities** of this group and the research cannot be carried out in a **non-vulnerable** group. In addition, this group should stand to **benefit** from the knowledge, practices or interventions that result from the research.

Question 27

# Scientific Requirements and Research Protocols Medical research involving human subjects must conform to generally accepted scientific ____, be based on a thorough knowledge of the scientific ____, other ____, and adequate ____ and, as appropriate, ____.

Answer 27

Medical research involving human subjects must conform to generally accepted scientific **principles**, be based on a thorough knowledge of the scientific **literature**, other **relevant sources of information**, and adequate **laboratory** and, as appropriate, **animal experimentation**.The welfare of animals used for research must be respected.

Question 28

Scientific Requirements and Research Protocols The ____ of animals used for research must be respected.

Answer 28

The **welfare** of animals used for research must be respected.

Question 29

Scientific Requirements and Research Protocols The design and performance of each research study involving human subjects must be clearly described and justified in a ____.

Answer 29

The design and performance of each research study involving human subjects must be clearly described and justified in a **research protocol**.

Question 30

Scientific Requirements and Research Protocols The protocol should contain a statement of the ____ considerations involved and should indicate how ____ have been addressed.

Answer 30

The protocol should contain a statement of the **ethical** considerations involved and should indicate how **the principles in this Declaration** have been addressed.

Question 31

Scientific Requirements and Research Protocols The protocol should include information regarding ____, ____, ____, ____, ____ and information regarding provisions for ____ subjects who are harmed as a consequence of participation in the research study.

Answer 31

The protocol should include information regarding **funding**, **sponsors**, **institutional affiliations**, potential **conflicts of interest**, **incentives for subjects** and information regarding provisions for **treating and/or compensating** subjects who are harmed as a consequence of participation in the research study.

Question 32

Scientific Requirements and Research Protocols The protocol should include information regarding provisions for ____ who are harmed as a consequence of participation in the research study. In clinical trials, the protocol must also describe appropriate arrangements for ____ provisions.

Answer 32

The protocol should include information regarding provisions for **treating and/or compensating subjects** who are harmed as a consequence of participation in the research study. In clinical trials, the protocol must also describe appropriate arrangements for **post-trial** provisions.

Question 33

# Research Ethics Committees The research protocol must be submitted for ____, ____, ____ and ____ to the concerned research ethics committee before the study begins. This committee must be ____ in its functioning, must be ____ of the researcher, the sponsor and any other undue influence and must be ____.

Answer 33

The research protocol must be submitted for **consideration**, **comment**, **guidance** and **approval** to the concerned research ethics committee before the study begins. This committee must be **transparent** in its functioning, must be **independent** of the researcher, the sponsor and any other undue influence and must be **duly qualified**.

Question 34

# Research Ethics Committees It (the Research Ethics Committee) must take into consideration the ____ of the country or countries in which the research is to be performed as well as applicable ____ norm and standards but these must not be allowed to reduce or eliminate any of the ____ for research subjects set forth in this Declaration.

Answer 34

It must take into consideration the **laws and regulations** of the country or countries in which the research is to be performed as well as applicable **international** norms and standards but these must not be allowed to reduce or eliminate any of the **protections** for research subjects set forth in this Declaration.

Question 35

# Research Ethics Committees The committee must have the right to ____ ongoing studies. The researcher must provide ____ information to the committee, especially information about any ____.

Answer 35

The committee must have the right to **monitor** ongoing studies. The researcher must provide **monitoring** information to the committee, especially information about any **serious adverse events**.

Question 36

# Research Ethics Committees No amendment to the protocol may be made without ____ and ____ by the committee.

Answer 36

No amendment to the protocol may be made without **consideration** and **approval** by the committee.

Question 37

# Research Ethics Committees After the end of the study, the researchers must ____ to the committee containing a summary of the study’s findings and conclusions.

Answer 37

After the end of the study, the researchers must **submit** a final report to the committee containing a summary of the study’s findings and conclusions.

Question 38

# Privacy and Confidentiality Every precaution must be taken to protect the ____ of research subjects and the ____ of their personal information.

Answer 38

Every precaution must be taken to protect the **privacy** of research subjects and the **confidentiality** of their personal information.

Question 39

# Informed Consent Participation by individuals capable of giving informed consent as subjects in medical research must be ____.

Answer 39

Participation by individuals capable of giving informed consent as subjects in medical research must be **voluntary**.

Question 40

# Informed Consent Although it may be appropriate to consult family members or community leaders, no individual capable of ____ may be enrolled in a research study unless he or she ____.

Answer 40

Although it may be appropriate to consult family members or community leaders, no individual capable of **giving informed consent** may be enrolled in a research study unless he or she **freely agrees**.

Question 41

# Informed Consent In medical research involving human subjects capable of giving informed consent, each potential subject must be adequately informed of the ____, ____, ____, any ____, ____, the anticipated ____ of the study and the discomfort it may entail, ____ and any other relevant aspects of the study.

Answer 41

In medical research involving human subjects capable of giving informed consent, each potential subject must be adequately informed of the **aims**, **methods**, **sources of funding**, any **possible conflicts of interest**, **institutional affiliations of the researcher**, the anticipated **benefits and potential risks** of the study and the discomfort it may entail, **post-study provisions** and any other relevant aspects of the study.

Question 42

# Informed Consent The potential subject must be informed of the right to ____ in the study or to ____ at any time without reprisal. Special attention should be given to the specific ____ of individual potential subjects as well as to the ____ to deliver the information.

Answer 42

The potential subject must be informed of the right to **refuse to participate** in the study or to **withdraw consent to participate** at any time without reprisal. Special attention should be given to the specific **information needs** of individual potential subjects as well as to the **methods** used to deliver the information.

Question 43

# Informed Consent After ensuring that the potential subject has ____, the physician or another appropriately qualified individual must then seek the potential subject’s ____, preferably in writing.

Answer 43

After ensuring that the potential subject has **understood the information**, the physician or another appropriately qualified individual must then seek the potential subject’s **freely-given informed consent**, preferably in writing.

Question 44

# Informed Consent If the consent cannot be expressed in writing, the non-written consent must be formally ____ and ____.

Answer 44

If the consent cannot be expressed in writing, the non-written consent must be formally **documented** and **witnessed**.

Question 45

# Informed Consent All medical research subjects should be given the ____ of being informed about the general outcome and results of the study.

Answer 45

All medical research subjects should be given the **option** of being informed about the general outcome and results of the study.

Question 46

# Informed Consent When seeking informed consent for participation in a research study the physician must be particularly cautious if the potential subject is in a ____ relationship with the physician or may consent under ____. In such situations the informed consent must be sought by an appropriately qualified individual who is ____ of this relationship.

Answer 46

When seeking informed consent for participation in a research study the physician must be particularly cautious if the potential subject is in a **dependent** relationship with the physician or may consent under **duress**. In such situations the informed consent must be sought by an appropriately qualified individual who is **completely independent** of this relationship.

Question 47

# Informed Consent For a potential research subject who is ____ of giving informed consent, the physician must seek informed consent from the ____.

Answer 47

For a potential research subject who is **incapable** of giving informed consent, the physician must seek informed consent from the **legally authorised representative**.

Question 48

# Informed Consent These individuals (incapable of giving consent) must not be included in a research study that has no likelihood of benefit for them unless ____, ____, and ____.

Answer 48

These individuals must not be included in a research study that has no likelihood of benefit for them unless **it is intended to promote the health of the group represented by the potential subject**, **the research cannot instead be performed with persons capable of providing informed consent**, and **the research entails only minimal risk and minimal burden**.

Question 49

# Informed Consent When a potential research subject who is deemed incapable of giving informed consent is able to ____ to decisions about participation in research, the physician must ____ in addition to the consent of the legally authorized representative. The potential subject’s ____ should be respected.

Answer 49

When a potential research subject who is deemed incapable of giving informed consent is able to **give assent** to decisions about participation in research, the physician must **seek that assent** in addition to the consent of the legally authorised representative. The potential subject’s **dissent** should be respected.

Question 50

# Informed Consent Research involving subjects who are ____ or ____ incapable of giving consent, for example, unconscious patients, may be done only if the physical or mental condition that prevents giving informed consent is ____. In such circumstances the physician must seek informed consent from the ____.

Answer 50

Research involving subjects who are **physically** or **mentally** incapable of giving consent, for example, unconscious patients, may be done only if the physical or mental condition that prevents giving informed consent is **a necessary characteristic of the research group**. In such circumstances the physician must seek informed consent from the **legally authorised representative**.

Question 51

# Informed Consent If no such (legally authorized) representative is available and ____, the study may proceed without informed consent provided that the specific reasons for involving subjects with a condition that renders them unable to give informed consent have been stated in the ____ and the study has been approved by ____. Consent to remain in the research must be obtained ____ from the subject or a legally authorised representative.

Answer 51

If no such (legally authorized) representative is available and **if the research cannot be delayed**, the study may proceed without informed consent provided that the specific reasons for involving subjects with a condition that renders them unable to give informed consent have been stated in the **research protocol** and the study has been approved by **a research ethics committee**. Consent to remain in the research must be obtained **as soon as possible** from the subject or a legally authorised representative.

Question 52

# Informed Consent The physician must fully inform the patient which aspects of their care are ____. The refusal of a patient to participate in a study or the patient’s decision to withdraw from the study must never adversely affect ____.

Answer 52

The physician must fully inform the patient which aspects of their care are **related to the research**. The refusal of a patient to participate in a study or the patient’s decision to withdraw from the study must never adversely affect **the patient-physician relationship**.

Question 53

# Informed Consent For medical research using ___ human material or data, such as research on material or data contained in biobanks or similar repositories, physicians must seek ___ for its collection, storage and/or reuse.

Answer 53

For medical research using **identifiable** human material or data, such as research on material or data contained in biobanks or similar repositories, physicians must seek **informed consent** for its collection, storage and/or reuse.

Question 54

# Informed Consent There may be exceptional situations where consent would be ___ or ___ to obtain for such research. In such situations the research may be done only after ___ and ___ of a research ethics committee.

Answer 54

There may be exceptional situations where consent would be **impossible** or **impracticable** to obtain for such research. In such situations the research may be done only after **consideration** and **approval** of a research ethics committee.

Question 55

# Use of Placebo The benefits, risks, burdens and effectiveness of a ____ must be tested against those of the ____, except in the following circumstances: Where ____, the use of placebo, or no intervention, is acceptable; or

Answer 55

The benefits, risks, burdens and effectiveness of a **new intervention** must be tested against those of the **best proven intervention(s)**, except in the following circumstances: Where **no proven intervention exists**, the use of placebo, or no intervention, is acceptable; or

Question 56

# Use of Placebo The benefits, risks, burdens and effectiveness of a new intervention must be tested against those of the best proven intervention(s), except in the following circumstances:: Where for compelling and scientifically sound ____ reasons the use of any intervention less effective than the best proven one, the use of placebo, or no intervention is ____ to determine the efficacy or safety of an intervention and the patients who receive any intervention less effective than the best proven one, placebo, or no intervention will ____ be subject to additional risks of serious or irreversible harm as a result of not receiving the best proven intervention. Extreme care must be taken to avoid abuse of this option.

Answer 56

Where for compelling and scientifically sound **methodological** reasons the use of any intervention less effective than the best proven one, the use of placebo, or no intervention is **necessary** to determine the efficacy or safety of an intervention and the patients who receive any intervention less effective than the best proven one, placebo, or no intervention will **not** be subject to additional risks of serious or irreversible harm as a result of not receiving the best proven intervention. Extreme care must be taken to avoid abuse of this option.

Question 57

# Post-Trial Provisions In advance of a clinical trial, sponsors, researchers and host country governments should make provisions for ____ for all participants who still need an intervention identified as ____ in the trial. This information must also be disclosed to participants during the ____.

Answer 57

In advance of a clinical trial, sponsors, researchers and host country governments should make provisions for **post-trial access** for all participants who still need an intervention identified as **beneficial** in the trial. This information must also be disclosed to participants during the **informed consent process**.

Question 58

# Research Registration and Publication and Dissemination of Results Every research study involving human subjects must be registered in a ___ before recruitment of the first subject.

Answer 58

Every research study involving human subjects must be registered in a publicly accessible database before recruitment of the first subject.

Question 59

# Research Registration and Publication and Dissemination of Results Researchers, authors, sponsors, editors and publishers all have ethical obligations with regard to the ____ of the results of research. Researchers have a duty to make ____ the results of their research on human subjects and are accountable for the ____ and ____ of their reports. All parties should adhere to accepted guidelines for ____.

Answer 59

Researchers, authors, sponsors, editors and publishers all have ethical obligations with regard to the **publication and dissemination** of the results of research. Researchers have a duty to make **publicly available** the results of their research on human subjects and are accountable for the **completeness** and **accuracy** of their reports. All parties should adhere to accepted guidelines for **ethical reporting**.

Question 60

# Research Registration and Publication and Dissemination of Results ____ and ____ as well as ____ results must be published or otherwise made publicly available.

Answer 60

**Negative** and **inconclusive** as well as **positive** results must be published or otherwise made publicly available.

Question 61

# Unproven Interventions in Clinical Practice In the treatment of an individual patient, where proven interventions ____ or other known interventions have been ____, the physician, after seeking expert advice, with informed consent from the patient or a legally authorised representative, may use an ____ intervention if in the physician’s judgement it offers hope of saving life, re-establishing health or alleviating suffering.

Answer 61

In the treatment of an individual patient, where proven interventions **do not exist** or other known interventions have been **ineffective**, the physician, after seeking expert advice, with informed consent from the patient or a legally authorised representative, may use an **unproven** intervention if in the physician’s judgement it offers hope of saving life, re-establishing health or alleviating suffering.

Question 62

# Use of Placebo The ____, ____, ____ and ____ of a new intervention must be tested against those of the best proven intervention(s), except in certain circumstances:

Answer 62

The **benefits**, **risks**, **burdens** and **effectiveness** of a new intervention must be tested against those of the best proven intervention(s), except in certain circumstances:

Question 63

# Research Registration and Publication and Dissemination of Results ____, ____ and ____ must be declared in the publication. Reports of research not in accordance with the principles of this Declaration should ____ be accepted for publication.

Answer 63

**Sources of funding**, **institutional affiliations** and **conflicts of interest** must be declared in the publication. Reports of research not in accordance with the principles of this Declaration should **not** be accepted for publication.

Question 64

# Unproven Interventions in Clinical Practice This (unproven) intervention should subsequently be made the object of research, designed to evaluate its ____. In all cases, new information must be ____ and, where appropriate, made ____.

Answer 64

This intervention should subsequently be made the object of research, designed to evaluate its **safety and efficacy**. In all cases, new information must be **recorded** and, where appropriate, made **publicly available**.

Question 65

# Overview Declaration of Helsinki, General Content (2+5)

Answer 65

1. Preamble 2. General Principles 1. Risks, Burdens, and Benefits 2. Vulnerable Groups and Individuals 3. Scientific Requirements and Research Protocols 4. Research Ethics Committees 5. Privacy and Confidentiality

Question 66

# Overview Declaration of Helsinki, Specific Content (5)

Answer 66

6. Informed Consent 7. Use of Placebo 8. Post-Trial Provisions 9. Research Registration and Publication and Dissemination of Results 10. Unproven Interventions in Clinical Practice