informed consent Process in CR

Guidelines for Obtaining Informed Consent for Clinical Research : 

Guidelines for Obtaining Informed Consent for Clinical Research By: Dr. Amit Bhatt Nexus-CRI

ICD Process : 

ICD Process Informed consent is a process, not just a form signed by prospective study subjects. Documents such as the Code of Federal Regulations describe the elements of informed consent, but lack substantive direction on the process of obtaining consent. The purpose of this article is to provide guidelines for obtaining informed consent. This guide can be useful to anyone involved in clinical research, particularly newcomers to the industry.

History : 

History Longest non-therapeutic experiment on human beings in medical history: The progress of untreated syphilis (1932-72). 399 poor African-American sharecroppers in rural Macon County, Alabama, USA.

History : 

History The men were told they were being treated for “bad blood”. Even after penicillin was discovered and found to be a miracle cure, the men were not treated or even told what they had. US government officials went to extreme lengths to insure that they received no therapy from any source. Presidential apology, May 1997

Nazi Prisoner Research During World War II : 

Nazi Prisoner Research During World War II Objectives of various trials: Effect of cold, heat, chemicals on men, women and children “Time to death” testing in response to stressors in healthy “volunteers” Organ transplant experiments on healthy “volunteers” Any information given (some?) is irrelevant because prisoners were forced to participate Outcome: 23 German scientists taken to court, 7 acquitted, 9 imprisoned, 7 given death sentence Nuremberg Code of 1947

Informed Consent in Human ResearchThe Origins : 

Informed Consent in Human ResearchThe Origins Before the 20th century, guidelines required physician’s need to adhere to acceptable medical standards Issue of patient’s agreement to the research never discussed Most requirements arose after the Nuremberg trials

Informed Consent in Human ResearchThe Origins : 

Informed Consent in Human ResearchThe Origins Emerges from the ethical principle of Respect for Persons Individuals be treated as capable of taking decisions for themselves (“autonomy”) Those with diminished autonomy be protected

What is informed consent? : 

What is informed consent? Informed consent is a PROCESS Involves Providing all relevant information to the volunteer/ patient The patient/ volunteer understanding the information provided Voluntarily agreeing to participate A basic right

Biomedical Research in HumansGuidelines for Informed Consent : 

Biomedical Research in HumansGuidelines for Informed Consent The Nuremberg Code, 1947 The Declaration of Helsinki, 1964 (2000) The Belmont Report, 1979 ICH GCP, 1997 ICMR Guidelines, 2000

The Nuremberg Code : 

The Nuremberg Code A set of 10 principles on research involving humans Developed after the horrors of Nazi experiments on humans became public Published in 1947

The Nuremberg Code and Informed Consent : 

The Nuremberg Code and Informed Consent The voluntary consent of the human subject is absolutely essential Person must have legal capacity to consent Should have “sufficient knowledge and comprehension” to make an “understanding and enlightened decision” Must be able to exercise “free power of choice”

Nazi Experiment : 

Nazi Experiment Inform the subject of The nature, duration and purpose The method and means All inconveniences and hazards Possible effects on health There should be no force, fraud, deceit, duress, coercion.

The Declaration of Helsinki : 

The Declaration of Helsinki A statement of ethical principles on research involving humans Published by the World Medical Association Developed from the Nuremberg Code Made by physicians First adopted at Helsinki in 1964

DOH : 

DOH Subjects must be Volunteers Informed participants Consent be obtained, preferably in writing If subject in a dependent relationship with the physician, consent be obtained by an independent physician

DOH : 

DOH Consent from legally acceptable representative required if subject: Minor Incapable of giving consent Physical or mental disability If subject is a minor, assent be taken, where possible

process : 

process When consent not possible prior to participation in research Approved by the “review committee” Consent must be obtained as soon as possible from the subject or a legally acceptable representative

The Belmont Report : 

The Belmont Report Ethical principles and guidelines for protecting humans in clinical research Developed by a commission set up in the US in the aftermath of the Tuskeegee Study becoming public Published in 1979

The Belmont Report and Informed Consent : 

The Belmont Report and Informed Consent Identifies three elements of the process Information Comprehension Voluntariness

Belmont report : 

Belmont report Information All information be provided Conditions under which information provided also important (rapid/ disorganized manner?) Comprehension Adapt presentation of information to subject’s capacities Investigators must ascertain comprehension Special provisions – immaturity, mental disability Voluntariness There must be no coercion or undue influence

ICMR Guidelines : 

ICMR Guidelines Participation must be voluntary Participants must be “fully apprised of the research” The investigator must obtain informed consent Responsibilities and information that must be provided Assent be obtained, where possible, for minors Requirement for consent can be waived by an ethics committee if risk is minimal (e.g. collecting data from subjects’ records)

Summary of all Guidelines : 

Summary of all Guidelines Guidelines require All relevant information be provided to subjects Ascertaining they understand what their participation means for them Voluntary consent Protecting vulnerable subjects with additional safeguards.

Process of ICD : 

Process of ICD The process of obtaining informed consent from subjects is a critical point of entry for research participants. Although the basic principles of obtaining informed consent transcend therapeutic areas and vulnerable patient populations, significant differences must be considered when research designs include individuals at increased risk.

Process : 

Process Special attention must be given to meeting the needs of vulnerable populations such as children, the critically ill, or the mentally impaired. The atmosphere for the family of a trauma patient during the first few critical hours of admission is far removed from the unhurried pace of the outpatient clinic. The focus of this article, however, is the process of obtaining consent from a population of patients who are not under duress at the time of consent.

Subject : 

Subject The subject may have been identified as part of a recruitment campaign. The subject may simply be part of a patient population being studied. The clinical trial may be offered as a treatment option after a patient has been given the facts concerning a diagnosis and prognosis.

Undue influence : 

Undue influence Although there are several ways that patients learn about clinical trial "little is known about the factors that influence decisions to participate in scientific research”. These factors include socioeconomic background, cultural traditions, literacy and language ability, and interactions with physicians and other healthcare professionals.

Risk benefit Ratio : 

Risk benefit Ratio The investigator should carefully weigh the consequences of trying to obtain consent after the patient has just been diagnosed with a life-threatening illness. A subject's ability to make decisions may also be affected by his/her emotional state. Emotional stress can be a cause of failure to consent. It is recommended that the subject be given a week to accept her diagnosis before discussing enrollment in the study.

Contd. : 

Contd. Emotional stress can be a cause of failure to consent. It is recommended that the subject be given a week to accept her diagnosis before discussing enrollment in the study. Subject's hesitation to ask detailed questions Variable presentation of the content Difficulty verifying the subject's comprehension.

Therapeutic Misconception : 

Therapeutic Misconception Subjects did not read the consent before signing, and a high percentage of volunteers admitted to not fully understanding the risks and not knowing what questions to ask. The concept of "therapeutic misconception" in research is another problem that has received much attention in both legal and bioethics literature.

Awareness of alternative Medicine : 

Awareness of alternative Medicine Generally, it is important that potential subjects are aware that research is not the only therapeutic alternative for them. Lack of subject understanding and comprehension is possibly compounded by the increasing regulations that govern the performance of study personnel and the cost pressures, meaning that there is ever-decreasing time available for study personnel to spend reviewing the consent with the subject.

Process : 

Process The informed consent process begins when a potential subject is first approached to participate in a clinical trial. Whether informed consent is obtained over the phone (remember-there may be a specific protocol for doing this at your institution), or in a doctor's office or hospital, the setting should be the same.

Contd. : 

Contd. It should be an unhurried, private atmosphere where the subject has time to review the document and ask questions. The subject should be approached in a respectful manner and the person obtaining consent should introduce themselves by name and role, stating the purpose of their communication. As already indicated, the timing of this process is very important.

Contd. : 

Contd. The person obtaining consent must have appropriate credentials and be qualified to do so. She/he should have experience in the field of study-otherwise, how will she answer questions posed by the subject? Additionally, this person should be familiar with good clinical practice guidelines for informed consent and with his/her own institutional review board's requirements for the process.

Contd. : 

Contd. The researcher should determine the ability of the potential subject to understand the information and give consent before proceeding further. If the subject does not read or speak English adequately, an assessment should be performed to determine the subject's needs.

TRANSLATION : 

TRANSLATION Use an effective process of translation and back-translation when an informed consent document must be translated from one language to another. This process must include adequate pretesting of the consent document to determine that it is comprehensible to individuals who will be recruited for a research project.

Document : 

Document Enlist the help of individuals who can act as "cultural experts" on ways in which to communicate difficult scientific concepts for study populations who may be unfamiliar with the biomedical problem being investigated. Keep the consent document as short as possible, using simple language and a format that is clear and understandable for potential research participants.

Contd. : 

Contd. The issue of using family members when there is a language barrier is a gray area. Most subjects feel more comfortable if one or more family members are available to help them with decision-making, though this is not always the case. Additionally, excluding family or friends from the discussion may eliminate bias for or against participation; however, this must be balanced with the subject's wishes. Tailor the discussion to the subject's needs.

Contd. : 

Contd. Discussing the research study The informed consent process is based on complete disclosure of the facts. During this process, the study coordinator or principal investigator should endeavor to establish a rapport and trusting relationship with the potential subject.

Review : 

Review The coordinator or investigator should thoroughly review each section of the informed consent with the study subject. The consent form is, in essence, a teaching tool-a nontechnical, understandable document, written at an eighth-grade reading level.

Contd. : 

Contd. It is imperative that subjects understand the nature of the research study, the risks and the benefits, alternatives to research, and their rights as study subjects. Study subjects need to read (or have read to them) and comprehend the informed consent document. Ensure that they understand the nature of the study, that is, why the research is being done and why they are being asked to participate.

Slide 40: 

The coordinator of the study should use whatever resources are available to promote subject understanding of the study such as, graphics, video, or even the device to be used, if possible. Care must be taken to avoid medical jargon that subjects could not possibly understand. Avoid presenting an overly positive (or negative) picture of the clinical trial for which consent is being obtained.

Slide 41: 

There is a growing body of data showing that research subjects have an unrealistic view of what their participation entails. Emphasis must be placed on the risks as well as the benefits. As has already been mentioned, subjects should understand the distinction between what is research and what is routine medical therapy. The idea is not to coerce but to provide the subject with the facts.

Slide 42: 

Finally, subjects should be allowed-and encouraged-to ask questions about the study. They should be able to take the document home with them if time permits. Consent should be obtained when the investigator is available to answer questions or address concerns. The principal investigator is ultimately responsible for all aspects of conducting the research.

Slide 43: 

The following information be included in the authorization or consent form the information that is provided or disclosed who may use or disclose the information who may receive the information each purpose of the use or disclosure of the information

Contd. : 

Contd. expiration date or event of the consent and authorization individual's signature and date the subject's right to revoke authorization the subject's right to refuse to sign authorization the fact that subsequent disclosures by the recipient may not be protected under ICH.

Template ICD : 

Template ICD Format of informed consent form for subjects participating in clinical trial Study Title: Study Number : Subject Initials :___________ Subject’s Name :____________ Date of births / age ________ Please initial box (Subject) I confirm that I have read and understood the information sheet date [ ] for the above study and have had the opportunity to ask questions I understand that my participation in the study is voluntary and that I [ ] am free to withdraw at any time, without giving any reason, without my medical care or legal rights being affected. I understand that the Sponsor of the clinical trial, others working on the [ ] Sponsor’s behalf, the Ethics Committee and the regulatory authorities will not need my permission to look at my health records both in respects of the current study and any further research that may be conducted in relation to it, even if I withdraw from the trial. I agree to this access. However, I understand that my identity will not be revealed in any information released to third parties or published.

Slide 46: 

I agree not to restrict the use of any data or results that arise from this study [ ] provided such a use is only for scientific purpose(s) 5. I agree to take part in the above study [ ] Signature (or Thumb impression) of the Subject/Legally acceptable Representative :_______________ Date : Signatory’s Name Signature of the Investigator : Date Study Investigator’s Name Signature of the witness Date

Resource Material : 

Resource Material Ethical guidelines for Biomedical Research on Human Subjects, Indian Council of Medical Research (ICMR) New Delhi 2000 The Gazette of India Extraordinary Part II Section 3(I) Research Ethics Training Curriculum R.Rivera, D. Borasky, R. Rice, Family Health International, 2001. http://www.fhi.org Designing Clinical Research An Epidemiologic Approach Ed Stephen, B Hulley, Steven R. Cummings Williams & Wilkins, Batlimore