APPENDIX TO REPORT AND RECOMMENDATIONS Research Involving Children THE NATIONAL COMMISSION FOR THE PROTECTION OF HUMAN SUBJECTS OF BIOMEDICAL AND BEHAVIORAL RESEARCH DHEW PUBLICATION NO. (OS) 77-0005 For sale by the Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 20402 This Appendix contains papers, reports and other materials that were reviewed by the Commission during its deliberations on re- search involving children. NATIONAL COMMISSION FOR THE PROTECTION OF HUMAN SUBJECTS OF BIOMEDICAL AND BEHAVIORAL RESEARCH MEMBERS OF THE COMMISSION Kenneth John Ryan, M.D., Chairman Chief of Staff Boston Hospital for Women Joseph V. Brady, Ph.D. Karen Lebacqz, Ph.D. Professor of Behavioral Biology Associate Professor of Christian Ethics John Hopkins University Pacific School of Religion Robert E. Cooke, M.D. David W. Louisell, J.D. President Professor of Law Medical College of Pennsylvania University of California at Berkeley Dorothy I. Height Donald W. Seldin, M.D. President Professor and Chairman National Council of Negro Women, Inc. Department of Internal Medicine University of Texas at Dallas Albert R. Jonsen, Ph.D. Eliot Stellar, Ph.D. Associate Professor of Bioethics Provost of the University and University of California at San Francisco Professor of Physiological Psychology University of Pennsylvania Patricia King, J.D. Robert H. Turtle, LL.B. Associate Professor of Law Attorney Georgetown University Law Center VomBaur, Coburn, Simmons & Turtle Washington, DC. NATIONAL COMMISSION FOR THE PROTECTION OF HUMAN SUBJECTS OF BIOMEDICAL AND BEHAVIORAL RESEARCH COMMISSION STAFF PROFESSIONAL STAFF SUPPORT STAFF Michael S. Yesley, J.D. Pamela L. Driscoll Staff Director Arlene Line Barbara Mishkin, M.A. Assistant Staff Director Marie D. Madigan Duane Alexander, M.D. Coral M. Nydegger Pediatrics Erma L. Pender Tom L. Beauchamp, Ph.D. Philosophy Lee A. Calhoun, M.A. Political Science Bradford H. Gray, Ph.D. SPECIAL CONSULTANTS Sociology Miriam Kelty, Ph.D. Robert J. Levine, M.D. Psychology Francis Pizzulli, J.D. Bonnie M. Lee Administrative Assistant Stephen Toulmin, Ph.D. James J. McCartney, M.A., M.S. Research Assistant Betsy Singer Public Information Officer TABLE OF CONTENTS 1. Research Involving Children . Survey Research Center 2. Law of Informed Consent in Human Experimentation: Children. George J. Annas Leonard H. Glantz Barbara F. Katz 3. The Ethics of Non-Therapeutic Clinical Research on Children Proxy Consent in the Medical Context: The Infant as Person . William G. Bartholome 4. The Competence and Freedom of Children to Make Choices Regarding Participation in Biomedical and Behavioral Research . Lucy Rau Ferguson 5. Rights, Duties, and Experimentation on Children: A Critical Response to Worsfold and Bartholome. Stanley Hauerwas 6. National Minority Conference on Human Experimentation. Conference Papers! Children and the Institutionalized Mentally Infirm . Henry W. Foster, Jr. Children and the Institutionalized Mentally Infirm. Crystal A. Kuykendall Resolution and Recommendations of the Workshop on Children 7. Responsibility in Investigations on Human Subjects, excerpt from the Report of the British Medical Research Council 8. Ethical Standards for Research with-Children, Society for Research in Child Development 9. Protection of Human Subjects, Policies and Proced- ures, Department of Health, Education and Wel- fare, Federal Register, Volume 38, No. 221, Part 11, November 16, 1973 10. Guidelines for the Ethical Conduct of Studies to Evaluate Drugs in Pediatric Populations, American Academy of Pediatrics, Committee on Drugs, 1977 11. Additional Readings 1 RESEARCH INVOLVING CHILDREN Survey Research Center University of Michigan Arnold S. Tannenbaum, Ph.D. and Robert A. Cooke, Ph.D., Principal Investigators Contract No. N01-HU-6-2110 Table of Contents page Summary of Findings . 2 Acknowledgements . 4 I. Types of Research . 6 II. Selection of Research Subjects . 9 III. Risks and Benefits of Research . 11 IV. Informed Consent . 15 V. Consent Forms . 20 VI, Subjects' and Proxies' Perceptions of Research . 23 VII. The Attitudes and Suggestions of Investigators, Subjects, and Proxies 28 Appendix . 33 1-1 Research Involving Children The data of this report have been obtained through interviews with 471 research investigators who have engaged in research involving children and. with 144 children-subjects or their proxies. These projects come from our sample of 61 institutions having general assurance of compliance with DREW regulations for protection of human subjects. The research investigators who have responded to our interviews are approximately 75 percent of the total number of such persons who were initially drawn in our sample. The representa- tion of research investigators in our final sample corresponds reasonably well to our initial design. (A more precise statement concerning the reliability of all samples in the study will be presented in the final report.) The final sample of subjects, however, does not correspond well to our design, in part because some institutions did not allow access to subjects and some investiga- tors were unable or unwilling to undertake the additional effort necessary to arrange our contact with subjects. We cannot claim, therefore, to have a representative sample of subjects or proxies. We nonetheless present data in this report obtained from subjects or proxies in order to illustrate the reactions of some of these persons to the research in which they participated. Projects differ from one another in the percent of subjects who were children. This report presents data furnished by investigators for all projects in which at least 25 percent of the subjects were under 19 years of age. Twenty eight percent of all of the projects that passed through our sample of IRB's during the period of July 1, 1974 to June 30, 1975 met this criterion (Table 1.1). In addition, we discuss data from all interviews taken with children or their proxies, not just those involved in projects in which at least 25 percent of the subjects were under age 19. The report is divided into seven sections. The first describes the types 1-2 of research involving children in a variety of institutional settings. The second concerns selection of subjects. The third section describes the risks and benefits of research as reported by researchers. The fourth section discusses informed consent and the fifth reviews the comprehensiveness and comprehensibility of consent forms used in research involving children. The sixth section discusses subjects' and proxies' perceptions of the research process. A seventh section presents the suggestions and opinions of investi- gators and some subjects/proxies. Accompanying the report is an appendix which presents a large number of tables, most of which are summarized in the report. Summary of Findings Projects that included 25 percent or more children represent about a quarter of all of the research that passed through review boards between July 1974 and June 1975. Fourteen percent of this research was reviewed by boards at children's hospitals and 52 percent by boards at medical schools, hospitals (other than children's) and other biomedical research centers. The remaining 34 percent was reviewed at universities (not including medical schools) and, to a lesser extent, at institutions for the mentally infirm and at behavioral research institutions. Approximately half of the projects involving children were primarily biomedical. Behavioral research accounts for about 40 percent of the research,. and the remaining small percentage entailed secondary analyses. Patients served as subjects in most of the projects reviewed at children's hospitals, medical schools, and other biomedical institutions. Patients also participated in about a third of the projects reviewed at universities (without medical schools) and at other behavioral research centers. In a large majority of projects, investigators reported that subjects were selected because of a specific condition or characteristic. 1-3 Most of the research, according to investigators, was designed primarily to benefit subjects directly or to benefit in the future persons with psycho- logical or medical conditions similar to those of the subjects. Almost a third of the projects were designed primarily for other purposes such as contributing to scientific knowledge. In approximately 70 percent of this latter group of projects, subjects were selected because they had a particular condition or characteristic. According to investigators, the changes most frequently requested by review committees concerned procedures for obtaining consent, occurring in- about a quarter of the projects. Consent procedures for secondary analyses were more likely to elicit recommendations for change than were procedures for other types of studies, the more frequent change here being the requirement that written consent be obtained from subjects. Oral and/or written consent was obtained in almost all projects in which children participated. Almost all of the projects from children's hospitals and about two thirds at other places employed proxy consent. Parents, relatives, and legal guardians were the most frequent proxies. Most investigators felt that proxy consent protected subjects "very well" or "fairly well," but a small percent indicated otherwise. Written consent forms were used in almost all research in children's hospitals end in about three quarters of the projects in other institutions. The purpose and procedures of the research were mentioned