Informed Consent in Clinical Researches

1. Informed Consent

2. Outline:
1. What is Informed Consent
2. Ethical basis: Why?
3.The consent process.
4. What is required to obtain a valid Informed
Consent?
5. Elements of informed consent.
5. Special situations
6. Conclusions

3. Informed consent is
??Processor aDocumenta

4. Consent is a continuous
process, not a one-time event.
A document.
useful information for subjects
names and contact information
reminder about study procedures

6. Facts
 Researchers need the person to enroll.
 Research can do harm.
 Protocols may require specific procedures
that may not be the best alternative.
 Researchers may be blinded to potential
alternatives.
 Therapeutic misconception of research
subjects.

7. •Applies the ethical principle:
respect for persons.
•Facilitates trust in the research
enterprise.
Informed consent

8. It is no longer an option.
It is now a must under the
current guidelines &
regulations

10. The Consent process:
Information
provided
Information
understood
Decision
made
Comprehension
monitored and
maintained

11. The Process of Consent:
 Choose the right environment and location to
obtain consent.
 Involve multiple health care personnel as
necessary.
 Include family members in the process as
warranted.
 Ensure that the subject or Legally Authorized
Representative is competent.

12. The Process of Consent:
(cont’d)
 Ensure the subject or LAR has sufficient
understanding.
 Continue the process of consent
throughout the study.

14. THE CONSENT PROCESS

15. The Plan
1. Identify obstacles to participation in study and
ways to overcome obstacles
2. Identify words subject may not understand
3. Compile “Frequently Asked Question” list
4. Decide who will do consent discussion
5. Decide where consent discussion will be held
6. Provide adequate time to explain study to
subject
7. Provide adequate time for subject to read and
consider and for questions to be answered

16. Consent Process Plan
.1Identify the obstacles to subject
participation and ways to overcome the
obstacles
TRANSPORTATION
FAMILY
WORK

17. Obstacles to
Participation
How Obstacles Will Be
Resolved
Generic Obstacles
1 1
2 2
3 3
Study Specific Obstacles
1 1
2 2
3 3

18. Consent Process Plan
2. Identify words subject may not
understand in ICF
Placebo
“a small animal like an amoeba”
IRB / IEC
“a committee that reviews your medical records to
see if you should be institutionalized”
Double blind
“Means being blind in both eyes”

19. “Double Blinded Placebo
Controlled study to measure
the efficacy of XXXXXX”
How can you translate it to Arabic ?
XXXXX

20. Consent Process Plan
3. Compile list of questions the subjects
may ask about the study and
appropriate responses

21. Consent Process Plan
4. Decide who will conduct consent
discussion
 Investigator may obtain consent
 Investigator may delegate responsibility to a
knowledgeable person.
 Investigator is ultimately responsible for assuring
informed consent has been appropriately obtained

22. Consent Process Plan
5. Decide where consent discussion will
be held
 Conduct in a quiet area
 Subject should have adequate
uninterrupted time
 Easy access to a study doctor
 Provide space for family members or friends to be
present during the consent discussion

23. Consent Process Plan
6. Provide adequate time to explain the
study and study procedures to the
subject
 Create a visual description when possible to foster
understanding
 Use patient education tools / brochures to assist in
discussion
 Explain the responsibilities of study participation

24. Consent Process Plan
7. Provide adequate time for subject to read
and consider
- No undue influence or coercion
- Allow subject to take consent home to discuss with
families or friends
8. Provide time for questions to be
answered

25. Consent Process Plan
-“How frequently will you need to come to the
clinic during the study?”
-“When can you decide if you want to discontinue from
the study?”
-“What medications must you avoid while in
the study?”
9. Use open-ended questions to assess if subject has
received adequate information to make an informed
decision

26. Consent Process Plan
10. Avoid closed-ended questions
 “Do you understand?”
 “Do you have any questions?”

27. Consent Process Plan
11. An important step towards successful
and ethical clinical research

28. When should Informed
Consent be obtained?
 Obtain consent after approval by Sponsor
and IRB / EC.
 Obtain consent prior to initiation of any
clinical procedures that are performed
solely for purpose of determining eligibility
for research

29. DateSubject or
Legally Acceptable
Representative
Person Conducting
Review of Consent
Date
DateWitness
Who can sign the Consent
Form?
Impartial Witness

30. Documentation of
Informed Consent Process
 Check that contact information is complete
on ICFs given to subject
 Provide subject with one of the copies of the
signed and dated ICF
 File the original signed and dated ICF in the
subject file
 Document study participation in medical
records of subject

31. Construction of a
complete and readable
consent form can be a
difficult task even in the
21st century

32. What is required to
obtain a valid informed
consent?

33. All studies must have informed
consent prospectively obtained
from each research subject (or
LAR).
 All types.
 Level of risk.
 Unless REC waives.

34.  Approved by the REC.
 Signed by the subject or LAR.
 A copy must be given to the person
signing the form.
Informed consent must be
documented using a written
consent form .

35. A good consent form:
 Complete information
 Accurate information
 In compliance with regulations and
guidelines
 Short simple sentences
 Simple understandable language
 Culturally sensitive language

36. Elements of
informed consent
Essential Additional

37. Voluntary
participation
Contact
information
Compensation
Confidentiality
Alternatives
Benefits
Risks
Purpose
Essential

38. Additional elements:
 Statement that there may be risks which
are unforeseeable
 Withdrawal criteria
 Additional costs to subjects
 Consequences of subject’s withdrawal
from research
 Statement that will be told of new findings
 Approximate number of subjects in study

40. No single model
represents a
Blue-Print for all countries

41. Common Findings:
 Too long consent form
 Too complicated language, Section
describing what procedures
 Not all the objectives mentioned in the
protocol are mentioned in the consent form
 Alternative are not mentioned.

42. Common Findings:
 Procedures do not accurately describe all
relevant issues – for example:
How many times for blood samples to
be withdrawn?
 Benefits of the research are over-stated
 Risks are not complete.

43. To be adequate an informed
consent requires that :
Subject
Autonomous
Decision
making capacity

44. Children
Pregnant women
Mentally ill
Prisoners
Minorities…
Vulnerable groups:

45. Children’s assent
To use children in research,
you must first obtain the
permission of the parent(s)
and then obtain assent
from the child.

46. Waiver of informed consent
 Waiving Documentation of Consent.
 Waiving Some elements of Consent.
 Waiving All of the elements of Consent.

47. Waiver of consent
Uncommon and exceptional

48. All studies Must have a consent
form or a waiver of consent.

49. More than Minimal Risk?
yes
Will waiving adversely affect subjects` rights?
yes
No
Practical to do research without waiver?
No
Information will be provided later” if appropriate”
yes
No
yesNo
No waiving
No waiving
No waiving
No waivingREC approve Waiver

50. Proper informed consent:
Disclosure
Understanding
Voluntariness

51. Proper informed consent:
Disclosure
Understanding
Voluntariness
What to tell
How to tell
Circumstances

52. Proper informed consent:
Disclosure
Understanding
Voluntariness
Challenges??
How to assess
Therapeutic
misconception/
randomization

53. Proper informed consent:
Disclosure
Understanding
Voluntariness
Free choice
No coercion
No undue inducement
Affected by:
 Power relation
 Restricted choices
 Illness
 Incentives

54. Challenges regarding
informed consent
Four main challenges:
Illiteracy
Culture,traditions and religion
Stored biological samples
Child assent

55. Informed consent and illiteracy
 In one of the clinical trials an old illiterate
villager told the researchers:
“I understood all what you said
and I agree to participate in
this trial but I used not to
sign any paper”
 What should the researchers
do??

56. Culture, traditions and religion
+
Stored biological samples
Local Research Ethics
regulations and LAW are
required

57. Children
 Every routine intervention that is
undertaken on the child requires
consent from the parents.
 If the child is able to understand
some aspects of the research
study, then his or her “assent”
must be obtained in addition to the
parents’ permission.

58. Child Assent
 What ages?
7 years – 14 years – 16 years – 18 years
– 19 years – less than 21 years???
 Written vs oral
 What information should be given?

59. Willowbrook Studies
 From 1966 to 1969, hepatitis studies were
carried out at the Willowbrook State
School, a NY institution for mentally
defective persons.
 These studies were designed to gain an
understanding of the natural history of
infectious hepatitis and subsequently to
test the effects of gamma globulin in
preventing or ameliorating the disease.

60.  The subjects, all children, were
deliberately infected with the hepatitis
virus; early subjects were fed extracts from
stools of infected individuals, and later
subjects received injections of more
purified virus preparations.

61. Willowbrook Studies
 Investigators defended the deliberate injections of
these children by pointing out that the vast majority
of them acquired the infection anyway while at
Willowbrook, and perhaps it would be better for
them to get infected under carefully controlled
research conditions.

62. The investigators also defended
the study by stating that:
They obtained parental consent
The children would receive a subclinical
infection followed by immunity to the particular
hepatitis virus.
The study had extreme value in
understanding an important disease that
would lead to a vaccine.

63. Willowbrook Studies
 During the course of these studies,
Willowbrook closed its doors to new
patients, but because the research
program had its own space, it was able to
admit new patients.
 Subsequently, parents were able to gain
admission for their children only if they
agreed to have their children enrolled in
the study.

64. Consent Letter ???
 Dear_______________:
 We are studying the possibility of preventing epidemics
of hepatitis on a new principle. Virus is introduced and
gamma globulin given later to some, so that either no
attack or only a mild attack of hepatitis is expected to
follow. This may give the children immunity against this
disease for life. We should like to give your child this new
form of prevention with the hope that it will afford
protection.
 Permission form is enclosed for your consideration. If
you wish to have your child given the benefit of this new
preventative, will you so signify by signing the form.
 Sincerely,
H. H. Berman, MD
We should like to give your child this new
form of prevention with the hope that it will
afford protection.
If you wish to have your child given the
benefit of this new preventative, ……

65. Case 1
 An investigator interviews a potential
research subject, explaining the purpose
of the study, the foreseeable risks, etc.
The subject smiles at the investigator and
says, “I am a simple man and I don’t
understand all this medical stuff and I
don’t think I ever will. But if you believe I
should let you do research on me, I will.”
 Would it be ethical to enroll that person
into the study?

66. Case 2
 A post graduate student was asked by
his professor to participate in the
control group of the professor’s clinical
trial.
 Is It Ethical to recruit the student?
 What should the student do?

67. Case # 3
 An investigator would like to measure
cytokines levels in bronchoalveolar lavage
fluid from patients with suspected lung
cancer lesions.
 He has a colleague who does
bronchoscopies on such patients and he
asks this colleague if he could obtain an
extra 15 cc of lavage fluid from these
patients when they undergo bronchoscopy
to diagnose the etiology of their lung
masses.

68.  Should informed consent be waived for the
obtainment of the additional 15cc of
lavage fluid?

69. Case # 4
 An oncologist-investigator is conducting a chemotherapy
clinical trial and is actively enrolling patients. Within his
clinical practice, at the request of the families, he does
not tell many of his patients their cancer diagnosis. Non-
disclosure of diagnosis also occurs even if the patients
receive chemotherapy.
 Based on this culture related factor, he requests from the
REC permission to enroll cancer patients in his
chemotherapy trials without telling them their cancer
diagnosis. He is concerned that a requirement to reveal
such information will hinder enrollment.
 Should the REC grant a waiver of consent?

70. Case # 5
 An investigator is recruited to do a
Phase 4 study for a drug company that
aims to collect data on side effects of a
recently approved drug for
hypertension.
 She will obtain data from the patients
she sees in her private clinic.

71. Case #5 Cont.
 The data she sends to the drug company
will not contain any identifying information
 Could informed consent be waived for this
study?

72. Case # 6
 An investigator is recruiting patients for a clinical trial
and he has discovered that his subjects are taking the
informed consent document to their private physicians,
who are persuading the subjects to withdraw from the
clinical trial. The subjects are told that the trial is too
risky and unethical.
 Hence, the investigator tells the REC that he will no
longer give his subjects the consent document. He
states that the larger number of dropouts is ruining the
statistical power of the clinical trial.
 Should the REC agree with the investigator?

73. Cases on Informed Consent
 An investigator wants to do a retrospective
medical record review of patients admitted
to the hospital during the last five years.
All data will be recorded anonymously.
 Should a waiver of informed consent be
granted?

74. BOTTOM LINE
The ultimate responsibility for
protection of the rights and welfare of
research subjects rests with the
principal investigator.
Obtainment of valid informed
consent is an important part of that
protection.

75. Honesty
builds
Trust

76. 76