HOW TO PRINT To print this page, use your browser's print button. To print the entire document, download the PDF or click here and use your browser's print button. SAMPLE LANGUAGE Sample 1 - Societal Benefit Sample 2 - phase I Sample 3 - phase I Sample 4 - phase I Sample 5 - phase I Sample 6 - phase II Sample 7 - phase II Sample 8 - phase III1 Sample 9 - phase III2 Sample 10 - phase III3 Sample 11- Surrogate Endpoints2 TOOLS & BACKGROUND MATERIALS King N, et. al.  Consent Forms and the Therapeutic Misconception. IRB Ethics and Human Research 2005.
MAIN POINTS The purpose statement should: Not overstate the goals of the study Reflect the study phase Include an understandable explanation of gene transfer

NIH GUIDELINES: The subjects should be provided with an accurate description of the possible benefits, if any, of participating in the proposed study. For studies that are not reasonably expected to provide a therapeutic benefit to subjects, the Informed Consent document should clearly state that no direct clinical benefit to subjects is expected to occur as a result of participation in the study, although knowledge may be gained that may benefit others."

DISCUSSION
Because of the experimental nature of gene transfer research, it is important for investigators to emphasize to potential participants the speculative nature of the potential benefits from the gene transfer intervention. To this end, the benefits section of the consent form should be labeled as Potential Benefits or presented as a question, such as Are there any possible benefits from this study?

Generic benefits discussions are commonly found in gene transfer research consent forms, but they should be avoided. Simple potential benefit statements, such as "You may or may not benefit from being in this study," or "Personal benefit cannot be predicted or guaranteed," do not provide sufficient meaningful information for potential participants in gene transfer research, particularly in early-phase studies. Such statements should be avoided whenever it is possible to provide more specific information about the nature and likelihood of potential benefits, if any, and their limitations, as described in the text of Appendix M-III-B-1-d and throughout this guidance section.

Vague statements like "Getting the gene transfer in this study may or may not improve your health, reduce your symptoms, or make you feel better" should also be replaced by appropriate discussion of specific disease aspects, since the meaning of "reduce symptoms", "improve health", and "feel better" may be interpreted differently by different potential participants.

Detailed discussion of potential benefits may assist potential participants in understanding the differences between receiving medical treatment and participating in research. An explicit statement of differences between treatment and research may also be helpful. In addition, investigators should distinguish between the ultimate goal of the line of research, the endpoints of the current study, and potential benefits to participants from the gene transfer. Without careful differentiation, the consent form could inappropriately convey the impression that the long-term goal of curing disease with gene transfer is identical to the potential benefit offered in a Phase I trial.

Societal Benefit: Many gene transfer consent forms fail to mention benefit to society. However, potential participants should always be informed that early phase studies are designed for scientific purposes and that those who participate in these studies may extend benefit to future patients by helping to advance scientific and medical knowledge. The investigator should distinguish between these benefits to society and potential benefits, if any, to participants.

Reducing Therapeutic Misconception: Characterizing an experimental study as treatment may be misleading to potential participants because it incorrectly implies that the experimental intervention is in fact a treatment -- or at least that it would not be tried unless there was some realistic expectation of its success for that potential participant. However, in a research context, benefits may not be anticipated with such confidence. This is especially true in early-phase trials, in new fields like gene transfer research, and when participants are seriously ill. Correcting inappropriate "treatment" language may help not only participants but also study personnel and oversight bodies avoid developing unrealistic expectations of clinical improvement from the gene transfer intervention.

Some examples of misleading language are:

• Your doctor is recommending this experimental treatment.
• Your doctor feels that treatment on this study will give you at least as good a chance as you might expect from other therapies.

Examples of misleading terms that may imply medical benefit include therapy, treatment, and patient. These terms should be replaced with terms such as gene transfer or gene transfer agent, and research participant, respectively.

Describing Potential Benefit for Different Phases and Designs: What is known about the potential benefits, if any, of a gene transfer intervention in a given study depend on the design and phase of the study and available evidence. Potential benefits discussions should be phase-specific. For combined Phase I/II studies, it is important to distinguish between the potential benefits of each phase.

Investigators should consider how to present information about prior experience and its limitations in the consent form so as to best inform potential participants. Previous experiences related to benefits in animal studies, and possibly even in vitro experience, may be relevant when the meaning and limitations of the findings are carefully described. Previous human experience is usually relevant, but should nonetheless be described carefully and its limitations addressed.

Uncertainty about the likelihood of the occurrence of direct personal benefit from the gene transfer intervention should always be mentioned. Especially in Phase I and II trials, it is appropriate to say that the primary purpose of the study is to produce benefits to society - that is, contributions to scientific knowledge and medical progress, and perhaps benefits to future patients.

• Phase I Study: Phase I trials involve the greatest uncertainty about the possibility of personal benefits, since existing data are limited. This uncertainty, and the early stage of the research, should be pointed out in the consent form. When presenting animal data, a general statement that humans and animals may respond very differently would be appropriate. The mere hope that the intervention will be therapeutic is not sufficient justification for suggesting the possibility of direct personal benefit. Depending on the specifics of the study, including existing data, study design, and power, it may be appropriate to state that direct personal benefit is unlikely, or that there will be none.
• Phase II Study: The possibility of direct personal benefits from the intervention may be somewhat better defined in Phase II studies. The consent form may include descriptions of suggestions of direct personal benefit that were discovered in Phase I. It should be acknowledged that the extent of experience is still limited; it is certainly still inappropriate to encourage the expectation of personal benefit.
• Phase III Study: The possible personal benefit statement for a Phase III trial should reflect the findings of the earlier phases. It should also acknowledge the results with a greater number of enrolled participants may be very different from those found in earlier phase trials.

Surrogate Endpoints: In gene transfer research, investigators most often seek to measure surrogate endpoints. However, these surrogate endpoints may not directly relate to any benefits that participants may clinically experience. Surrogate endpoints should not be described as benefits to participants unless there is a well-established, direct link to a clear health benefit. The challenge of discussing potential benefits lies in explaining the relationship, or lack thereof, between what the investigators seek to measure and what participants might experience. Whenever appropriate, investigators are encouraged to discuss explicitly and specifically the nature and extent of clear clinical benefits that potential participants may be expecting, in order to explain what expectations are reasonable and why, and what expectations are not reasonable and why.

SAMPLE LANGUAGE

Sample 1 - Societal Benefit

This study is meant to answer scientific questions about gene transfer for your disease. The results may give investigators information to use in future research, even if the gene transfer does not work. Some people find potential societal benefits like these a good reason to participate in this study. Please consider whether you think that as well.

Sample 2 - Phase I

The gene transfer you get in this study is not likely to change the natural course of your disease. This study is not meant to be a treatment for your disease. Instead, the investigators hope that the information learned from this study can benefit patients with [condition] in the future.

Sample 3 - Phase I

The purpose of this study is to test the safety of this gene transfer and to see if we can successfully put the gene into cells of people with [condition]. Treating your disease is not the purpose of this study. It is very unlikely that getting the gene transfer in this study will improve your health or [specific symptoms].

Sample 4 - Phase I

This study is not intended to benefit you directly. Investigators simply want an understanding of gene transfer for [condition]. Information about the amount of DNA needed and the effects of the gene transfer agent will be critical for further studies in the future. Getting the gene transfer in this study will not improve your health or [specific symptoms].

Sample 5 - Phase I

The reason for doing this study is to test the safety of different doses of gene transfer given to participants with [condition]. Although there is some evidence that the gene transfer injections could help [achieve surrogate endpoint] in some participants, we do not know if that will happen to you. Even if it does, the good effect would probably be small and not last long. However, it is very unlikely that this will happen. Benefit to you is not the goal of this study. Instead, we want to see if the study injections are safe. We also want to provide a foundation for future studies of these injections. We hope to benefit future patients with [condition].

Sample 6 - Phase II

Earlier studies support the safety of the gene transfer, but it is far too early to say whether it will help you at all. Even if it does, it is far too soon to know how much it may help and how long any benefit might last.

Sample 7 - Phase II

This is a Phase II study. It is the first systematic attempt to find out if this gene transfer will help individuals like you. You should not enroll in this study with any expectation that you will personally benefit.

Sample 8 - Phase III

Earlier research shows that this intervention may help individuals like you. However, we are not sure there will be any helpful effects. If there are any, we do not know how great those effects might be, or how long they might last. You should keep this uncertainty in mind as you decide whether you want to participate in this research.

Sample 9 - Phase III

This is a Phase III trial. It is an attempt to identify the extent and duration of benefit of this intervention. Any hope you have of gaining a meaningful personal benefit should be just a hope and not an expectation.

Sample 10 - Phase III

We cannot predict if you will gain any personal benefit from getting this gene transfer. Earlier studies show that the experimental gene transfer agent may shrink some tumors. This could decrease cancer-associated symptoms or prolong life for a time. However, the gene transfer may have no good effects on your disease at all. If your disease becomes worse, or if the side effects from the gene transfer become too great, or if there is any other reason to think that participation in this research is not in your best interest, we will stop your participation so that you can be treated with standard therapy.

Sample 11 - Surrogate Endpoints

In this study we are measuring [surrogate endpoint-SE]. We hope that a change in this measure will have [beneficial clinical effect] on this disease. But because this study is short, we do not know if changes in [SE] will change how participants in this study feel. We also do not know if [SE] will last for longer than a short time. It is also possible that for participants whose disease is very severe, a beneficial effect might not be felt very much or at all.