|NIH Guidance on Informed Consent
For Gene Transfer Research
NIH GUIDELINES: "The subjects should be provided with a detailed explanation in non-technical language of the purpose of the study and the procedures associated with the conduct of the proposed study, including a description of the gene transfer component."
Whenever applicable, the consent form and process should attempt to make clear to potential participants how research participation differs from being treated for health problems outside of the context of the study. This topic is also addressed in the Alternatives section.
Organization of Procedures Section: It is especially important in early-phase research, such as most gene transfer studies, to distinguish standard treatments from investigational interventions, and tests and measurements provided as part of clinical care from those related to the research study. Institutional review boards (IRBs) and institutional biosafety committees (IBCs) can provide guidance on how to differentiate between these activities. Using separate consent forms, or separate consent form sections, for the research component and standard treatment component is one reasonable way to distinguish between the two.
Avoiding Improper Language: Because gene transfer interventions, like other investigational interventions in early-phase trials, are unproven and have not yet been studied for efficacy, they should not be referred to as treatments.
Some examples of improper language are:
Alternative language reinforcing the experimental character of gene transfer should be chosen appropriately for a given protocol. Possible alternatives to the above examples might be:
Dosing Group Designs and Cohort Assignments: Many Phase I studies utilize dose escalation to determine a safe gene transfer agent dosage amount. If the study involves dose escalation, the investigator should explicitly state to which dosage cohort the potential participant will be assigned, the dose level to be received, and any potential risk-benefit balance for that particular cohort. In providing this information, the investigator should describe and explain dose escalation designs for the following reasons:
Other Study Designs: Many Phase III studies involve such features as randomization, inclusion of control groups, use of placebos, and blinding. All of these features should be explained simply and clearly in the consent form and process. Double-blind design explanations should include the information that the blind may be broken if necessary to protect the participant's health and welfare. IRBs and IBCs can provide guidance and sample language on blinding and randomization.
Procedures Language: In order to simplify consent forms, researchers are encouraged to consult resources like the Simplification Guide to Medical Terms that suggest replacements for terms that are difficult to understand and, thus, require explanation or substitution. In addition, dosage information should be as precise as possible; terms like low, medium, or high dose should be quantified in terms that are most informative to potential participants.
Sample 1 - Dose Escalation Design
We do not know the highest dose of the gene transfer agent that is safe. To find out we will give the gene transfer agent to [number] participants at one dose level. If that is safe we will raise the dose given to the next group of participants. The dose you will get will depend on how many participants get the agent before you and how they react. The investigator will tell you this information. This will help you think about possible harms and benefits. Since the gene transfer intervention is experimental, what is likely to happen at any dose is not known.
Sample 2 - Randomization to Experimental or Control Arm
It is not clear whether experimental gene transfer will be more effective than standard treatment. For this reason, you will be randomly assigned (like the flip of a coin) to one of two groups: the experimental group (gene transfer) or control group (standard treatment). You will have a 50% chance of being assigned to either group.