Informed Consent Considerations for Certain Types of Studies
Certain types of studies have special and important informed consent considerations. These are in addition to those considerations already discussed and the Principal Investigators should consider all of these elements when preparing a consent form.
The nature of some studies requires that the full purpose not be revealed to the subject until the study is completed. Such deliberate withholding of information is permitted only if the subject is informed that this is the case and agrees. This must be clearly stated in the consent form, along with the plan for when and how the complete information will be shared with the subject. Research based on deception or incomplete disclosure should be thoroughly justified and discussed with the IRB reviewer assigned to primary review of the study.
The informed consent document for drug trials must ensure that subjects understand that the drug is investigational, that its benefits for the condition are unproven, and, if applicable, that the physician/ investigator may have a potential conflict of interest. In Phase 1 trials, subjects must understand that the primary purpose of Phase 1 trials is generally to determine safety and pharmacy of the drug rather than provide a direct benefit to subjects.
Principal Investigators should use the generic/pharmacological name(s) of the agents, not the trade name(s). This also applies to the names of drug(s) used in the title of the project. The dose/dosage range of drugs to be administered must be clearly stated in the consent form. Availability of experimental drug(s) to the subject following the end of the subjects' participation and/or the close of the study and how the cost will be covered must also be clearly stated.
In epidemiologic studies, the IRB requires that the information provided to prospective subjects include descriptions of the kind of data that will be collected, the identity of the persons who will have access to the data, the safeguards that will be used to protect the data from inappropriate disclosure, the risks that could result from disclosure, whether identifiers will be collected, and whether they will be contacted again in the future. In long term studies, the IRB asks Principal Investigators to present a plan to obtain continuing consent from subjects at critical intervals ( e.g. , where the protocol is altered, new information becomes available). The initial consent at the beginning of a study usually will not suffice over an extended period of time.
Principal Investigators conducting genetic research must submit a proposed consent form that addresses these issues and should also discuss the following issues in the protocol, as applicable.
- If children are directly involved ( e.g. , with blood draws, biopsies, interviews), whether they will benefit directly from participating in the project.
- If extended family members are involved: (a) how they will be contacted and recruited in a way that does not unduly influence or coerce them to participate; (b) whether there are confidentiality issues involved ( e.g. , extended family members may not know an individual is sick or has a specific condition) and, if so, how they will be handled; and, (c) what measures can be taken to minimize family pressure on children in the extended family to participate.
- What information families will receive at what point in the research and the meaning of the information, e.g. , diagnostic, predictive, or reproductive implications. How interim or inconclusive results will be handled. Many genetic studies will not yield information that will be clinical useful to the subjects for some time.
- If some information may be given to each subject , state what information subjects will receive and when during the study. For example, will test information be conveyed separately to each subject upon receiving results, or only after the study is completed. Indicate if this information will represent only that which pertains to each subject or if it will be aggregate data from all study subjects.
- Whether subjects or family members will be given the choice to receive or not to receive study information or information about themselves. If they will have that choice, an option for noting their choice must be in the consent.
- Whether there are psychological risks ( e.g. , anxiety, confusion) associated with the research and the results obtained. If so, an explanation of how the information will be given to families in a way that will minimize these risks and the supports available to the subjects after they receive the information, i.e. , genetic counseling. If children are directly involved in the project, an explanation of how the data will be gathered and conveyed to them in a way that minimizes self-doubt and anxiety.
- Whether there are social risks ( e.g. , jeopardy to insurability, employability, damage to familial relationships) associated with the research and the results obtained. If so, how the research data will be protected from third parties, such as employers and insurance companies, and steps that the subjects should take to assure that potential economic risks are minimized. If extended family members are to be studied, what methods will be used to protect family members from unauthorized disclosure of medical or other personal information about themselves to other family members?
- State the possible clinical implications of receiving the test results. If appropriate, include the level of certainty that a positive test result serves as a predictor of the disease being studied.
- Whether there is a possibility of incidental findings , such as paternity or information about diseases or conditions other than the one(s) under study, and, if so, an explanation of how this information will be handled.
- An explanation of whether research findings will be disclosed to the subject's physician for clinical use . If they will have that choice, an option for specific consent for this must be included with a location to note their choice in the consent form.
- An explanation of how data/samples will be handled : (a) if a subject wishes to withdraw from a genetic study after it has begun; (b) if a subject wishes to withdraw from a genetic study after the project has been completed; and (c) if either the current Principal Investigator or another investigator wishes to use the research data/samples from this project for different research purposes.
- An explanation of whether or not personal identifiers will be maintained with the tissue or DNA specimens or not, recorded as part of the study records, or if links to personal identifiers will be maintained in a master list. Describe what personal identifiers will be recorded, such as name, medical record number, social security number or other code. Describe whether or not a subject would be re-contacted and given information from the specimens. If so, under what circumstances.
HIV/AIDS Related Research
Principal Investigators should ensure that study information that identifies the subject is not disclosed without the subject's consent. Principal Investigators should consider whether additional safeguards are necessary when research involves subjects in the later stages of the HIV-related illness, since the illness can cause dementia. Principal Investigators should also ensure that there is a mechanism for dealing with changes in mental capacity and continuing consent, if necessary.
If your study involves a single X-ray procedure for which standard wording is provided by the RSC you may use the exact wording provided. The consent form will not need to be reviewed by the Radiation Safety Committee subcommittee (HIRE - Human Investigations Involving Radiation Exposure). You must however, send them an electronic copy of the protocol and consent form(s) after the study is approved by the IRB.
If you are not using a single procedure- you must obtain approval from the RSC prior to being allowed to enroll subjects. You must provide their approval to the IRB-HSR.
Randomized Trials and Placebos
For randomized trials, the consent form should state the fact that subjects may be kept unaware of their treatment assignments in "blinded" studies and research involving placebos. Ethical considerations demand that subjects be informed when their assignment will be random, the percent chance they have of receiving both the experimental therapy and the alternative treatment, and that one of the possible consequences of participation is that the group to which they are assigned may receive the less effective intervention. Further, subjects should be told who will know whether they are receiving the placebo or the active agent. In a double-blinded trial, for example, subjects should be told that neither they nor the Principal Investigator will know whether they are receiving the placebo or the experimental therapy.
In studies involving a placebo washout, subjects should be told that at some point during the study all subjects will receive placebo treatment; Principal Investigators but not subjects will know when subjects are receiving placebos for washout purposes.
Use of Biological Specimens and Tissue Banking
Types of Human Biological Specimens
Most human biological specimens come from samples collected for diagnostic or therapeutic procedures, but other sources can include autopsies, volunteer donors, or materials collected and shared by other researchers.
- The term "biospecimen" is used widely and encompasses a full range of human specimen types including:
- Sub-cellular components such as DNA or RNA
- Cells or tissues from any part of the human body
- Organs such as liver, bladder, kidney, heart, placenta, etc.
- Gametes (ova and sperm)
- Embryos and fetal tissues
- Breast milk
- Exhaled air
- Bodily products such as teeth, hair, nail clippings, sweat, urine, feces
- Blood and blood fractions: plasma, serum, buffy coat, red blood cells
- Saliva and buccal cells
- Exceptions: Organisms, such as bacteria and viruses, isolated from human specimens are not human biological specimens.
Tissue Banks and Repositories
Various terms are used to designate the storage sites for human biological collections. The most common are defined below.
- Repository is a term usually applied to large formal collections of specimens and/or data. Examples include:
- The National Pathology Repository
- The Cooperative Human Tissue Network
- Tissue bank generally refers to smaller collections of specimens, which may be specific to an institution, disease, or even to specimens in a researcher's freezer.
Approvals Needed to Collect and/or Bank Human Specimens
If you are involved in collecting specimens from research subjects or intend to receive specimens from clinicians for banking purposes, you will need to obtain protocol approval from the IRB.
- Federally funded or cooperative group banks usually have well-defined prioritization and distribution methods. Be prepared to provide a Letter of Intent (LOI) or a study protocol describing your research plan. Applications are generally reviewed by an oversight committee and judged on scientific merit, statistical validity, the investigator's ability to conduct the proposed research, and the appropriateness of the sample size requested to accomplish the research goals.
- Departmental/Division banks and investigator-maintained collections may not have well-established application or distribution policies and may not be obligated to share specimen resources at all. Contact the tissue bank's administrator to find out how to obtain specimens.
- Commercial Tissue Banks: Specimens may be available for purchase from commercial sources.
- Private Collections: Individual researchers who are collecting specimens in your area of research may be willing to provide them. Contact the researcher directly to find out if collaboration is an option and the conditions for transferring or sharing specimens.
Informed Consent Issues
The informed consent form for the collection of biological specimens should ask subjects whether:
- the tissue may be kept for use in research to learn about, prevent, treat or cure a particular disease;
- the tissue may be kept for research about other health problems and
- if someone from UVa may contact the subject in the future to ask him/her to take part in more research.
The consent should also obtain a description of:
- whether tissue specimens will be stored for future research, maintained in a repository or used to establish a cell line, or otherwise how the DNA information from tissue specimens will be utilized in this study.
- where the tissue specimens will be stored; specify the location within the hospital or outside of the hospital.
- the purpose of storing the tissue
- what types of research you or others might use these specimens for in the future.
- who will have access to the DNA information from tissue specimens collected
- who will control distribution of the tissue
- what will happen to stored specimens if the Principal Investigator leaves the present institution.
- an explanation of whether or not personal identifiers will be maintained with the tissue or DNA specimens or not, recorded as part of the study records, or if links to personal identifiers will be maintained in a master list.
- what personal identifiers will be recorded, such as name, medical record number, social security number or other code.
- whether or not a subject would be re-contacted and given information from the banked specimens. If so, under what circumstances.
- what will be done with the study specimens at any point during the study in the event of a subject's withdrawal ( e.g. , the entire specimen/cell line could be removed from the study, identifiers could be removed, or information from the aggregate of study data already generated by a particular specimen could be removed).
*Taken from UVa IRB-HSR Research Guidance