63. Consent: Questions and answers
R E L AT E D E N T R I E S
Consent (page 169), Consent: Checklist (page 177), Consent: Disclaimers and notifications (page 181), Consent: Principles and purpose (page 183), Consent: Process (page 185), Consent: Types (page 189)
QUESTIONS AND ANSWERS
What if a person is randomized and the consent form has not been signed?
Answer:The lapse of protocol is serious. The presumption, while sometimes wrong, is that there was no consent in the absence of documented evidence of consent. Data for the person should be expunged from the study dataset.
The fact of the breach should be reported to the IRB of record. The action of the IRB will depend on the seriousness of the breach. It will not likely be understanding of any instance in which persons are enrolled absent consent and is likely, in such cases, to require a halt of enrollment pending a review of procedures for consent. If the breach was of a procedural nature where consent was obtained but the form was not signed, the action is likely to be less severe.
The investigator should write a memo to the patient’s file noting the breach, the reason or likely reason for the breach, when and how it was noted, when it was reported to the IRB, and the action taken. The processes for consent and documentation of the fact of consent should be reviewed and tightened to prevent future occurrences.
You are well into the trial when you discover the consent form contains information that is wrong. What should you do?
Answer:The course of action depends on when the deficiency is noted. Consents for persons enrolled and still under followup should be updated and the fact of the updating should be documented. Persons still to be enrolled should be consented based on correct information as contained in a revised, IRB approved, consent form.
Persons, when consented, were told they would be treated and followed for one year and then separated from the trial. Later on, investigators decide to treat and follow everyone to a common closing date regardless of when they enrolled. What to do?
Answer:The change requires reconsent. The reconsent should detail the reason for the change and what the change means to persons enrolled. Persons not willing to commit to the new design but willing to remain in the trial under the old design should have that option.
When should a person be informed of the treatment they received in masked trials?
Answer: The answer varies depending on the trial. The expectation, except where persons are told otherwise on enrollment, is that persons will be unmasked when they finish in the trial. The closeout design and procedures for unmasking should be reviewed and approved by IRBs before implementation.
IRBs can be expected to be wary of proposals in which patients are not informed of treatment assignment on completion of treatment and followup. Likewise, plans in which persons are to be informed at some point after the close of the trial are suspect in the absence of means for maintaining contact after close of the trial.
The treatment should be unmasked on separation if the information is of value to the subject or to persons advising the subject on care subsequent to the trial.
A person withdraws from a double-masked trial and asks to be informed of the treatment to which assigned. What do you do?
Answer:There should be efforts to turn the request aside. Part of the reason for doing so is that unmasking during the trial increases the chance of treatment-related feed back
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bias. The risk of such bias can be reduced by masking schemes in which it is possible to unmask an assignment without any peripheral unmasking. That is possible with med Id labeling but not with bin Id labeling (for definitions see Drug packaging and labeling, Page 117).
The issue of unmasking should be covered during consent. If unmasking is not to be done until the end of the trial, persons should be so informed when enrolled. They should know that they may withdraw from the trial at any time but that they will not learn of the treatments they were receiving until the end of the trial except in special circumstances involving time critical treatment decisions.
What if that same person asks to have his/her data removed from the trial?
Answer: Again, under ideal circumstances that issue is covered in consent. Persons enrolled should know that they can withdraw but that data collected on them will not be expunged from the study database.
What is a deconsent and when is it indicated?
Answer:Deconsent is the opposite of consent. It takes place on separation from the trial at its conclusion. In the case of treatment trials, the information imparted relates to treatment received (including identity of assigned treatment in the case of a trial involving masked treatment), findings from the trial and relevance for the person departing, and observations and recommendations regarding the person’s subsequent care and treatment.
What is a reconsent and when is it indicated?
Answer:Reconsent is a reaffirmation of the willingness of a person to continue in a study under new or revised circumstances. The new or revised circumstance may be due to the addition of procedures heretofore not in force, an extension of the period of treatment or of followup, or the addition or deletion of a treatment in the randomization schedule.
Reconsents are necessary when changes in study procedures have the potential of causing persons to withdraw from participation because of the change. Reconsents should be documented in the same way consents are documented.
A treatment is stopped during the trial because it is seen as inferior to the control treatment. Patients on the treatment are informed of the result and taken off treatment. Is there a need to reconsent patients not effected by the change?
Answer: Yes. The information could cause persons not effected by the change to withdraw when informed of the action.
Midway into your trial, another set of investigators, doing a similar trial, announce that they are stopping the trial because the test treatment is superior to the control treatment. The results in your trial do not provide evidence of superiority. What is your duty to patients in your trial?
Answer:They should be informed of the result, that the trial they are in will continue, and why continuation is indicated.
A serious side effect, not anticipated when the trial was designed, is reported outside the trial. The side effect has not been noted to-date in patients in your trial and is not mentioned as a possibility in the existing consent form. Should the form be revised to include mention of the side effect? Should persons already enrolled be informed of the possibility of the side effect?
Answer:Yes to both questions.
A person agrees to be randomized. The randomization is issued and the person declines treatment. What do you do?
Answer:There is nothing to be done. Persons have the right to decline treatment, and that right remains regardless of having consented to randomization. The randomization is counted to the treatment group indicated by the assignment, and the person is counted as enrolled.
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A person believes that she has not been adequately informed as to risks or requirements of the study. What to do?
Answer: Try to address the concerns in a polite and forthright manner. Remind the person of her rights and options, including those to withdraw and to take her complaint to others, including the investigator’s IRB.
What if the complaint relates to injury caused by study?
Answer:The consent form should include a statement on what persons can expect and not expect in relation to redress of study-related injuries. The ‘‘boiler plate’’ on injury, as contained in consents for studies reviewed by the IRB for the Johns Hopkins Hospital and Medical School, is:
If you want to talk to anyone about this research study because you think you have not been treated fairly, or you have been hurt by joining the study, or you have questions about the study, you should call the principal investigator, (name), at (phone no), or call the Office of the Joint Committee on Clinical Investigation at 410 955–3008 or call the Francis Scott Key Medical Center Institutional Review Board for Human Research at 550–1853. Either the investigator or the people in the Committee office or IRB office will answer your questions and/or help you find medical care for an injury you feel you have suffered. The Johns Hopkins University, The Johns Hopkins Hospital, The Francis Scott Key Medical Center (other), and the Federal Government do not have any program to provide compensation to you if you experience injury or other bad effects which are not the fault of the investigator
Investigators are required to clear amendments to protocols through IRBs before they are implemented. There are dozens of changes to forms and procedures over the course of trials. Which among those rise to the level of amendments in the eyes of IRBs?
Answer:Changes having potential of adversely affecting the benefit/risk ratio for persons studied, changes likely to reduce the willingness of persons to enroll or remain under study, and introduction of questions considered to be sensitive in nature.
Which changes require changes to consent documents and procedures?
Answer:Changes having potential of adversely effecting the benefit/risk ratio of being studied as well as any changes likely to reduce a person’s willingness to enroll or remain under study.
If changes are to be reviewed and approved by one’s IRB before implementation, what does one do when the need for change is time critical and where it is unwise to wait for IRB approval before proceeding?
Answer:In matters of urgency, investigators are expected to act without the time delays in waiting for IRB approvals. In such cases, IRBs are informed after-the-fact and of the reasons for the action.
Enrollment and Followup