Eric Kodish

Perceptions of cancer patients and their physicians involved in phase I trials.

PURPOSE In an attempt to understand some of the complex issues related to the participation of cancer patients in phase I trials, and the perceptions of patients toward these trials, we conducted a pilot survey study of 30 cancer patients who had given informed consent to participate in a phase I trial at our institution. Concurrently, the oncologists identified by the surveyed patients as responsible for their care were surveyed as well. PATIENTS AND METHODS Twenty-seven of 30 consecutive patients agreed to and completed the survey. Patients were surveyed before they received any investigational agents. Eighteen oncologists participated in this survey study. RESULTS Eighty-five percent of patients decided to participate in a phase I trial for reasons of possible therapeutic benefit, 11% because of advice/trust of physicians, and 4% because of family pressures. Ninety-three percent said that they understood all (33%) or most (60%) of the information provided about the trials in which they had decided to participate. Only 33% were able to state the purpose of the trial in which they were participating, with patients able to state the purpose of phase I trials being more educated (P = .01). Surveyed oncologists had wide-ranging beliefs regarding expectations of possible benefits and toxicities for their patients participating in phase I trials. CONCLUSION Cancer patients who participate in phase I trials are strongly motivated by the hope of therapeutic benefit. Altruistic feelings appear to have a limited and inconsequential role in motivating patients to participate in these trials. Cancer patients who participate in phase I trials appear to have an adequate self-perceived knowledge of the risks of investigational agents. However, only a minority of patients appear to have an adequate understanding of the purpose of phase I trials as dose-escalation/dose-determination studies.

Near-total human face transplantation for a severely disfigured patient in the USA

BACKGROUND Multiple reconstructive procedures are common for the reconstruction of complex facial deformities of skin, soft tissues, bony structures, and functional subunits, such as the nose, lips, and eyelids. However, the results have been unsatisfactory. An innovative approach entailing a single surgical procedure of face allograft transplantation is a viable alternative and gives improved results. METHODS On Dec 9, 2008, a 45-year-old woman with a history of severe midface trauma underwent near-total face transplantation in which 80% of her face was replaced with a tailored composite tissue allograft. We addressed issues of immunosuppressive therapy, psychological and ethical outcomes, and re-integration of the patient into society. FINDINGS After the operation, the patient did well physically and psychologically, and tolerated immunosuppression without any major complication. Routine biopsy on day 47 after transplantation showed rejection of graft mucosa; however, a single bolus of corticosteroids reversed rejection. During the first 3 weeks after transplantation, the patient accepted her new face; 6 months after surgery, the functional outcome has been excellent. In contrast to her status before transplantation, the patient can now breathe through her nose, smell, taste, speak intelligibly, eat solid foods, and drink from a cup. INTERPRETATION We show the feasibility of reconstruction of severely disfigured patients in a single surgical procedure using composite face allotransplantation. Therefore, this should be taken in consideration as an early option for severely disfigured patients. FUNDING None.

Children's Competence for Assent and Consent: A Review of Empirical Findings

This narrative review summarizes the empirical literature on childrens competence for consent and assent in research and treatment settings. Studies varied widely regarding methodology, particularly in the areas of participant sampling, situational context studied (e.g., psychological versus medical settings), procedures used (e.g., lab-based vs. real-world approaches), and measurement of competence. This review also identified several fundamental dilemmas underlying approaches to childrens informed consent. These dilemmas, including autonomy versus best interests approaches, legal versus psychological or ethical approaches, child- versus family-based approaches, and approaches that emphasize consent versus those that emphasize assent, have implications for the measurement of childrens competence and interpretation of findings. Recommendations for future research in the area of childrens informed consent include the use of diverse samples and control groups, development of multidimensional and standardized measures of competence, utilization of observational methods and longitudinal designs, examination of noncognitive aspects of childrens competence, and comparison of childrens competence for treatment and research decisions.

Long-term follow-up care for pediatric cancer survivors

Progress in therapy has made survival into adulthood a reality for most children, adolescents, and young adults diagnosed with cancer today. Notably, this growing population remains vulnerable to a variety of long-term therapy-related sequelae. Systematic ongoing follow-up of these patients, therefore, is important for providing for early detection of and intervention for potentially serious late-onset complications. In addition, health counseling and promotion of healthy lifestyles are important aspects of long-term follow-up care to promote risk reduction for health problems that commonly present during adulthood. Both general and subspecialty pediatric health care providers are playing an increasingly important role in the ongoing care of childhood cancer survivors, beyond the routine preventive care, health supervision, and anticipatory guidance provided to all patients. This report is based on the guidelines that have been developed by the Childrens Oncology Group to facilitate comprehensive long-term follow-up of childhood cancer survivors (www.survivorshipguidelines.org).

The world's experience with facial transplantation: What have we learned thus far?

The objective of this review article is to summarize the published details and media citations for all seven face transplants performed to date to point out deficiencies in those reports so as to provide the basis for examining where the field of face transplantation stands, and to act as a stimulus to enhance the quality of future reports and functional outcomes. Overall long-term function of facial alloflaps has been reported satisfactorily in all seven cases. Sensory recovery ranges between 3 and 6 months, and acceptable motor recovery ranges between 9 and 12 months. The risks and benefits of facial composite tissue allotransplantation, which involves mandatory lifelong immunosuppression analogous to kidney transplants, should be deliberated by each institution’s multidisciplinary face transplant team. Face transplantation has been shown thus far to be a viable option in some patients suffering severe facial deficits which are not amenable to modern-day reconstructive technique.

Ethical issues in phase I oncology research: A comparison of investigators and institutional review board chairpersons

PURPOSE Phase I research trials assess the safety of agents never before administered to humans. In the field of oncology, this practice raises several important ethical questions. We examined the ethics of these trials by surveying phase I oncology investigators and institutional review board (IRB) chairpersons at major cancer research centers around the country. METHODS Questionnaires were mailed to 78 investigators and 47 chairpersons to obtain their views on the ethical propriety of conducting phase I oncology research, and on institutional practice regarding these trials. The response rate was 68% in each group. RESULTS The majority of each group reported that phase I oncology trials face no more scrutiny or resistance in their institutions IRB process than other research protocols. Nevertheless, IRB chairpersons were more likely than investigators to favor special procedural safeguards to protect subjects in phase I oncology trials. Nearly all respondents agreed that although actual medical benefit was very uncommon, most patients entered for a chance at a therapeutic effect. Investigators were more likely than chairpersons to report that patients obtained psychologic benefit from participation in phase I trials. CONCLUSION Although individual IRB chairpersons and oncology investigators may have important differences of opinion concerning the ethics of phase I trials, these disagreements do not represent a widespread area of ethical conflict in clinical research.

Comparison of the Informed Consent Process for Randomized Clinical Trials in Pediatric and Adult Oncology

PURPOSE To compare the informed consent processes for phase III pediatric and adult oncology clinical trials in view of the critical importance of human subjects protection in both pediatric and adult cancer care. Findings are discussed in terms of the opportunities for improving pediatric and adult oncology informed consent. PATIENTS AND METHODS A total of 219 subjects are reported on. Adult oncology patients made up 36.1% (n = 79) of the sample. Pediatric surrogates made up the remaining 63.9% (n = 140). Subjects in both studies were observed and audiotaped in conversation with their oncologists, and interviewed afterwards. Comparisons between the adult and pediatric subjects were done using chi(2) statistics and t tests. RESULTS Differences between the pediatric and adult informed consent processes were found. Adult oncology decision makers were, on average, more fully informed and more actively engaged by their oncologists. Pediatric decision makers were, however, given more information about survival/cure, randomization, and voluntariness. Comprehension difficulties were more frequent among pediatric decision makers. Suggestions for improvement are made in view of the differences between adult and pediatric oncology research environments. CONCLUSION Ongoing efforts to improve the ethical framework of clinical cancer research need to take into account the key differences between pediatric and adult oncology informed consent. More research needs to be done to explore the differences between adult and pediatric informed consent processes in oncology.

The Return of Research Results to Participants: Pilot Questionnaire of Adolescents and Parents of Children with Cancer

The offer to return research results to participants is increasingly recognized as an ethical obligation, although few researchers routinely return results. We examined the needs and attitudes of parents of children with cancer and of adolescents with cancer to the return of research results.

A survey of language barriers from the perspective of pediatric oncologists, interpreters, and parents

Oncologists in the US increasingly face the challenge of communicating with non‐English speaking parents of children with cancer. This study explores this challenge from the perspectives of a sample of pediatric oncologists, interpreters, and Spanish‐speaking parents of children with newly diagnosed leukemia.

Providing Research Results to Participants: Attitudes and Needs of Adolescents and Parents of Children With Cancer

PURPOSE There is an increasing demand for researchers to provide research results to participants. Our aim was to define an appropriate process for this, based on needs and attitudes of participants. METHODS A multicenter survey in five sites in the United States and Canada was offered to parents of children with cancer and adolescents with cancer. Respondents indicated their preferred mode of communication of research results with respect to implications; timing, provider, and content of the results; reasons for and against providing results; and barriers to providing results. RESULTS Four hundred nine parents (including 19 of deceased children) and 86 adolescents responded. Most parents (n = 385; 94.2%) felt that they had a strong right to research results. For positive results, most wanted a letter or e-mail summary (n = 238; 58.2%) or a phone call followed by a letter (n = 100; 24.4%). If the results were negative, phone call (n = 136; 33.3%) or personal visits (n = 150; 36.7%) were preferred. Parents wanted the summary to include long-term sequelae and suggestions for participants (n = 341; 83.4%), effect on future treatments (n = 341; 83.4%), and subsequent research steps (n = 284; 69.5%). Understanding the researcher was a main concern about receiving results (n = 145; 35.5%). Parents felt that results provide information to support quality of life (n = 315; 77%) and raise public awareness of research (n = 282; 68.9%). Adolescents identified similar preferences. CONCLUSION Parents of children with cancer and adolescents with cancer feel strongly that they have a right to be offered research results and have specific preferences of how and what information should be communicated.