Informed Consent 1

Running Head: HUMAN SUBJECTS

Human Subject’s Comprehension of Informed Consent

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Statement of the Problem
A primary protection of the rights of clinical research subjects revolves around the concept respect for persons and the provision of informed consent (Belmont Report, 1979). Legal and ethical policies and guidelines enforce that research participants give informed consent prior to voluntary enrollment in a research study (Code of Federal Regulations,1999). However, the informed consent process presents some major challenges for study participants and research staff. Several papers have addressed problems with the current process. Brady (2003) identifies the following issues: subject’s hesitation to ask detailed questions, variable presentation of the content, and difficulty verifying the subject’s comprehension. Also, a survey performed by Center Watch in 2002 found that 14% of subjects did not read the consent before signing it 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” (Joffe, Cook, Cleary, Clark, & Weeks, 2001) in research is another problem that has received much attention in both legal and bioethics literature. It is important that potential subjects are aware that participation in clinical research is not the only therapeutic alternative for them (Horng & Grady, 2003). Lack of subject understanding and comprehension is compounded by busy physician schedules and increased patient volumes in private practice and clinical research. This causes a time constraint, which ultimately affects the patients ability to ask questions and discuss research participation procedures. The research study details, including all risks and benefits should be communicated to the study subjects during the informed consent process. Subjects should also be given the opportunity to ask questions and time to process the information before they make a

Informed Consent 3 commitment. 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 (Appelbaum, 2002). The idea is not to coerce but to provide the subject with facts to facilitate an informed decision about enrolling or not enrolling in a clinical research study. Many factors can influence the study participant’s willingness to sign the informed consent document. These factors include socioeconomic background, cultural traditions, literacy and language ability, and relationships with physicians and other healthcare professionals. What, when, and how information is presented can affect a subject’s comprehension of research and potential enrollment (Bosk, 2002). The investigator should carefully weigh the consequences of trying to obtain consent after the participant has just been diagnosed with a life threatening illness. A subject’s ability to make decisions may be affected by their emotional state and can be a cause of failure to consent. A subject should be given time to accept the diagnosis before discussing study enrollment. Study findings indicate that risk levels influence a subject’s willingness to participate in clinical research (Trechan et al., 2003). Negative media attention such as popular press coverage of an adverse event that occurred during a research study at John Hopkins, may adversely affect decisions to participate (Karigan, 2001). Getz (2002) suggests that subjects who successfully complete other clinical trials are more likely to consent again. The Food and Drug Administration (FDA), The National Institutes of Health (NIH), and The Office for Protection from Research Risks (OPRR) play important and complementary roles to oversee research and protect human subjects. These agencies work with Institutional Review Boards (IRBs) to ensure that people who agree to participate in studies fully understand the Informed Consent 4 nature of the research and voluntarily consent to participate. Research institutions such as academic health centers and universities have the ultimate responsibility to ensure that clinical investigators adhere to this informed consent process. Unfortunately, there are no standard tools to assess the results of the consent process. This prevents the IRBs from monitoring progress and efficiency of the investigators and determining if other barriers exist that may cause lack of comprehension.
Statement of Significance Conducting a study of the consent process at l will enable the GCRC compliance office, the Committee on Research Involving Human Subjects (CORIHS-IRB), and the NIH to better ascertain if participants are being informed as per government guidelines. If no problems are detected, then the questionnaire can be used periodically as a standard measure for monitoring. However, if the survey shows that issues need to be addressed, this study will pinpoint what areas need attention.
Once the problem areas are revealed, educational interventions can be applied specifically to remedy each situation. At the present time, we are not sure how much the research participants understand therefore to insure patient safety and educate the research community it would be very beneficial to conduct the study.
Statement of Purpose
The purpose of this study is to answer the following research questions: To what extent do research participants comprehend the informed consent?
What are the perceived barriers that influence a human subject from being informed?

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Review of Literature
Overview
This review of literature will summarize the quality of informed consent in research. It will focus on research subject comprehension of the informed consent process to evaluate if volunteers have been informed. This review will identify barriers to understanding: subject education level, study team facilitation of information, and consent difficulty level. Areas in need of further research will be addressed to help increase comprehension. Research on Human Subject’s Comprehension of the Informed Consent Detailed informed consent is a requirement of patient participation in clinical research, however patients commonly fail to understand and recall the information conveyed. Studies have shown some reasonable steps investigators must take to ensure comprehension include; using clear, non-technical language at an appropriate reading level, in the participant’s native language, and providing opportunities to ask questions throughout the trial (Sreenivasan, 2003). Joffe, Cook, Cleary, Clark, and Weeks (2001) conducted a study to determine the quality of the informed consent in cancer trials. Results showed that 70% did not understand the protocol treatment details and 25% did not understand risk benefit issues. While issues about the relationship between knowledge and study enrollment are unclear, it is apparent that the subject’s full understanding of the protocol is essential if ethical standards of informed consent are to be met (Daugherty, 1999). Research on Barriers to Comprehension: Subject Education Level, Consent Ease in Readability, and Investigator Delivery of Study Information

Informed Consent 6 Studies have documented that the majority of consent documents for research are written at a reading level above that of the majority of the U.S. population (Sreenivasan, 2003). Coyne, Xu, Raich, Plomer, Dignan, Wenzel, Fairclough, Habermann, Schnell, Quella, and Cella (2003) randomly assigned 207 cancer patients to either an easy-to-read consent or the standard consent. Results showed that informed consent documents can be modified to be easier to read without omitting critical information. Also, patient anxiety and satisfaction can be affected by the consent document. Other studies have found that increased knowledge was associated with college education, use of the U.S. National Cancer Institute consent form template (easier to read format), not signing the consent form at initial discussion, presence of a nurse, and careful reading of the consent form (Joffe et al., 2001). Video presentation of the informed consent information was found to significantly increase study knowledge in subjects with lower levels of education (Curbow, Fogarty, McDonnell, Chill, Benz Scott, 2004). Investigators often report that they experience difficulty with explaining trials, and audiotape audits have shown that in many consent interviews critical information is omitted or poorly presented. Jenkins, Fallowfield, Souhami, and Sawtell (1999) analyzed 82 audiotaped discussions in which consent was being conducted for participation in a randomized clinical trial. In most, the concept of the trial was introduced by describing uncertainty about treatment decisions. The median duration of the consent process was 15 minutes and patient understanding was never checked in 83%. Tomamichel, Sessa, Herzig, de Jong, Pagani, and Cavalli (1995) analyzed the content of the informed consent interviews and concluded that the investigator’s willingness to perceive and Informed Consent 7 discuss the emotional needs, complaints, or objections of patients needed to be improved. The patient was not encouraged in decision making. Verheggen, Jonkers, and Kok (1996) interviewed 32 Principal Investigators who recruited 198 subjects for clinical trials. These investigators were skeptical of the subject’s abilities to comprehend 15 of 20 elemental aspects of informed consent. Of the 32, only 6 felt that the consent procedure ensured that subject’s understood the procedures of the trial; 22 felt that understanding was incomplete, and 4 were uncertain about levels of understanding. Patient experiences and perceptions of being recruited to Phase I and Phade II clinical trials have been analyzed in a qualitative study by Cox (2002). The major factors influencing trial participation were a thorough description of the trial by investigators and study staff and the utility of the written informed consent as a reference.
The Current Study A questionnaire will be used to determine whether a research participant’s encounter with the informed consent process resulted in an understanding of the study that they are enrolled in. This study will differ from others that have been conducted because a large number of participants will be normal healthy volunteers (controls). This removes the emotion and anxiety factors caused by the illness, which can affect comprehension and the decision process. Also, the study will include any protocol on the GCRC not just one specific trial. The idea for this research project is to detect any trends that may be causing this miscomprehension issue so that interventions can be implemented to resolve it.

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Methods
Research Design A descriptive, non-experimental approach has been chosen. A cross-sectional survey will be used to determine the prevalence of miscomprehension of the informed consent process in research subjects. This cross-sectional design works best for this study because it can provide descriptive information within a short time frame and can measure correlations between the different variables (comprehension versus educational level, investigator/study team participation, nursing reinforcement). The observations and data collection will then be used to make some recommendations for change. Because the method being used is a “snapshot in time” and the study is being conducted on newly consented research participants, history, maturation, and subject mortality will not impact the internal validity of the study. The tool developed to measure comprehension and understanding of the informed consent will not include racial, cultural, language, or intelligence bias; thus reducing the potential for instrumentation validity concerns. The cross-sectional design allows for control of subjects and measurements therefore making it easier to control external validity. One researcher will be administering the questionnaire to study participants for continuity purposes. No special attention or extra conversation will be provided as to reduce the potential for Hawthorne and researcher effects. The participants for this study will be matched to the population demographics for Suffolk County as reported by the United States Department of Commerce Census Bureau. This should satisfy generalizability. The cross-sectional research design also promotes reliability. This one time only predominately close-ended and true/false survey eliminates Informed Consent 9 confounding factors such as fatigue, subject motivation issues, and repeated test learning. Since the survey is self administered tester skill and different testers will not present an issue. The testing environment will be a simple interview room without any noise or visual distractions.
Sample Characteristics Sample Selection and Sample Size: a convenience sample of 100 people will be recruited into the study. Eligibility Criteria: Inclusion • Male and female adults, 18 years or older • Signed consent to enroll in a research study at the GCRC • Participation in only one research study at the time of this survey • English primary language • Ability to read and write English at an 8th grade level Exclusion • Males and females < 18 years of age • Not consented to participate in a research study • Participation in more than one research study at the time of this survey • English secondary language
Recruitment Procedures The convenience sample will be recruited from the study population on on the 12th floor in the south tower.

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Data Collection Procedures
Data will be collected using an in-person self-report questionnaire. Information will be recorded on teleforms and scanned into a database. There are no standard measurement tools for outcome assessment of the consent process. Investigators performing similar studies have used surveys tailored specifically for their protocols, however, validity of these tools have not been established. A new survey will be designed to determine the extent of research participant’s comprehension of informed consent at the
Study Variable Definition and Measurement The dependent variable in this study is comprehension of the informed consent. The independent variables are subject education level, investigator/study team involvement in consenting subject, and nursing personnel facilitation of the study. The survey will consist of 20 questions on the basic elements of the informed consent as specified in the Code of Federal Regulations. Other elements surveyed will be questions about the consent process (time spent reading document, clarity, questions answered) and demographic characteristics (age, sex, education).
Data Management and Analysis For variables at least 5-point rating scales will be summarized with means and standard deviations. Comparisons of means will be based on Student t-tests or Wilcoxin rank-sum tests if normality assumptions are suspect. Categorical variables will be summarized as counts, proportions, or percents and Pearson chi-square tests and Fisher’s exact test will be used to make statistical comparisons. Findings will be considered statistically significant at p-values less than or equal to 5% and parameters will be estimated with corresponding 95% confidence intervals. Informed Consent 11
SPSS software will be used and all data will be stored in a locked cabinet in a locked office on the GCRC.
Expected Results I expect that more than half of the subjects enrolled in this study will understand their consent forms and be satisfied with the informed consent process. I think that very few people if any will have felt pressured to participate. At least 25% will not understand questions pertaining to the elements of the informed consent as described in the Federal Regulations and a portion of these people will not have read the consent. Results of this study might uncover important flaws in the consent process. Interventions can then be introduced to educate participants and study personnel to facilitate comprehension and ultimately, ensure human subject safety.
Limitations
Several limitations might affect the interpretation of this study. First, the study is being conducted at the GCRC, of which characteristics could differ at other sites. Second, participants are being asked to complete the survey at any time point after consenting to participate in a study on the research unit. Understanding of the consent concepts might be better at the time of signing rather than several days or even weeks later. Third, since direct observation of the consent process is not being performed it might be difficult to assess whether lack of comprehension is due to investigator/study team failure to inform or participant’s lack of recall.

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Time Frame Literature Search 10 hours Reading Articles 30 hours Hypothesis 10 hours Research Design 25 hours Tool development 10 hours Data Collection & 25 hours Administering the Questionnaire Analyzing the Data 20 hours Practicum Write-up 5 hours 135 hours
Protection of Human Subjects and HIPAA The study being conducted is research involving human subjects. Therefore, all required IRB paperwork must be submitted and approved by the Committee for Research Involving Human Subjects (CORIHS) at to protocol initiation. This proposal will qualify for the exempt review category because the study involves survey procedures for which there are no foreseeable risks to the participants.
*CORIHS human subject compliance training completed (see attached confirmation).

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References
Appelbaum, P.S.(2002). Clarifying the Ethics of Clinical Research: A Move toward Avoiding the Therapeutic Misconception. American Journal of Bioethics, 2(2), 22-24.
Bosk, C.L.(2002). Obtaining Voluntary Consent for Research in Desperately Ill Patients. Medical Care, 40(9), 64-68.
Brady, J.S. (2003, January). Multimedia Delivery Can Enhance the Consent Process. Applied Clinical Trials, 36-42.
Cox, K. (2002). Informed Consent and Decision Making: Patient’s Experiences of the Process of Recruitment to Phases I and II Anti-Cancer Drug Trials. Patient Education and Counseling, 46, 31-38.
Coyne, C.A., Xu, R., Raich, P., Plomer, K., Dignan, M., Wenzel, L.B., Fairclough, D., Habermann, T., Schnell, L., Quella, S., Cella, D. (2001). Randomized, Controlled Trial of an Easy-to-read Informed Consent Statement for Clinical Trial Participation: A Study of the Eastern Cooperative Oncology Group. Journal of Clinical Oncology, 21(5), 836-842.
Curbow, B., Fogarty, L.A., McDonnell, K., Chill, J., Benz Scott, L. (2004). Can a Brief Intervention Improve Breast Cancer Clinical Trial Knowledge and Beliefs? Social Science and Medicine, 58(1), 193-205.
Daugherty, C.K. (1999). Impact of Therapeutic Research on Informed Consent and the Ethics of Clincial Trials: A Medical Oncology Perspective. Journal of Clinical Oncology, 17, 1601-1617.
Getz, K.A. (2002, November). Informed Consent Process: A Survey of Subjects Assesses Strengths and Weaknesses. Applied Clinical Trials, 30-36. Informed Consent 14
Horng, S. & Grady, C. (2003). Misunderstanding in Clinical Research: Distinguishing Therapeutic Misconception, Therapeutic Misestimation, and Therapeutic Optimism. IRB: A Review of Human Subjects Research, 25(1), 11-16.
Jenkins, V.A., Fallowfield, L., Souhami, A., Sawtell, M. (1999). How Do Doctors Explain Randomized Clinical Trials to Their Patients? European Journal of Cancer, 35, 1187-1193. Joffe, S., Cook, F.E., Cleary, P.D., Clark, J.W., Weeks, J.C. (2001, November). Quality of Informed Consent In Cancer Clinical Trials: A Cross-Sectional Survey. The Lancet, 358, 1772-1777
Karigan, M.(2001). Ethics in Clinical Research: The Nursing Perspective. American Journal of Nursing, 101(9), 26-31.
Office for Protection from Research Risks. (1979, April 18). Ethical Principles and Guidelines For Research Involving Human Subjects. The Belmont Report, B. 1.
Sreenivasan,G. (2003). Does Informed Consent to Research Require Comprehension? The Lancet, 362, 2016-2018.
Tomamichel, M., Sessa, C., Herzig, S., de Jong, J., Pagani, O. Y. W., Cavalli, F. (1995). Informed Consent for Phase I Studies: Evaluation of Quantity and Quality of Information Provided to Patients. Annal of Oncology, 6, 363-369.
Treschan, T.A., Scheck, T., Kober, A., Fleischmann, E., Bickenber, B., Petshcnigg, B., Akca, O., Lackner, F.X., Jandl-Jager, E., Sessler, D.I. (2003). The Influemce of Protocol Pain and Risk on Patient’s Willingness to Consent for Clinical Studies: A Randomized Trial. Anesthesia & Analgesia, 96(2), 498-506. Informed Consent 15
U.S. Department of Health and Human Services. (1999). General Requirements for Informed Consent. Code of Federal Regulations, 45 CFR 46.116.
Veheggen, F. W., Jonkers, R., Kok, G. (1996). Patient’s Perceptions on Informed Consent and the Quality of Information and Disclosure. Patient Education and Counseling, 29, 137-143.