Consent Of Subjects Research Articles

Chapter 7: Informed consent and xenotransplantation clinical trials

This essay explores the meaning and implications of informed consent in xenotransplantation clinical trials from both ethically justifiable and international perspectives. In international and national codes and guidelines involving human subject research and in the laws of many nations, the informed consent of research subjects is obligatory. Its moral foundations include and also extend beyond respect for individual persons as autonomous agents in Western nations. Axioms regarding the value of human life and duties to protect innocent and vulnerable persons from harm, duress, and deceit underlie Western individualism and are broadly shared in many non-Western cultures. Accents on family and/or community consent in China and other nations are compatible with individual consent as long as family and community consent supplement, rather than replace, individual consent. Reflecting its moral foundations, informed consent in medical research is rightly characterized as "voluntary" or "freely given" informed consent because it encompasses researchers' disclosure and subjects' comprehension of all the relevant information about the protocol that reasonable persons would want to know in order to freely and affirmatively enroll in the research. The interplay between these conceptual foundations of informed consent and the realities of xenotransplantation research defines what the nature and functions of consent should be in xenotransplantation clinical trials. Because these trials involve a complex body of medical information, numerous procedures, numerous risks (associated with failure rates, immunosuppression, xenogeneic infections, and so on) and the subject's obligation to abide by extensive national and international precautionary guidelines, informed consent should be enacted as an organized, sequential, thoughtfully paced, jargon-free process of communication. The features and functions of consent forms or consent documents should accord with this process. Rather than being virtually equated with informed consent, consent documents should be utilized as templates of relevant, essential, and understandable information that contribute to comprehension and voluntary enrollment. In xenotransplantation clinical research, the consenting process must cover a large number of topics, including treatment choices, participation information, study procedures, information about risks associated with immunosuppression, xenogeneic infections, discomforts, and other matters. In addition, due to infectious risks, subjects are obliged to 10 post-protocol responsibilities. Two of the three unique moral issues regarding informed consent in xenotransplantation trials involve what to do to minimize post-protocol infectious risks and what to do about international and national guidelines that affirm the subject's right to withdraw from participation in medical research at any time. The third moral issue centers on issues involving the enrollment of children and mentally incapacitated adults. The other chapters in this consensus statement demonstrate that, morally and logically, favorable harm-benefit determinations precede considerations of informed consent. When these harm-benefit assessments are favorable enough to warrant the onset of clinical trials, informed consent emerges as a pivotal moral precondition for these trials.

Critical evaluation of informed consent forms for adult and minor aged whole blood donation used by United States blood centers

Blood donation is a medical procedure with attendant risks, and thus blood donors should undergo acceptable informed consent. There are no guidelines for the informed consent forms (ICFs) for whole blood donors or for parental consent forms (PCFs) for minor age blood donors. The goal of the study was to determine if the majority of the generally accepted elements of informed consent are provided to volunteer allogeneic whole blood donors in the United States. ICFs and PCFs along with their accompanying general information forms (GIFs) from nonmilitary blood collection establishments for allogeneic whole blood donation were collected throughout the United States and scored using a system based on the essential elements of informed consent derived from guidelines of consent for research subjects. The overall score for each ICF and PCF was obtained. Twenty-one ICFs and 37 PCFs from 48 states representing major collection centers within the United States were scored. The mean score for the common essential elements ICFs was 35 percent (range, 10%-80%) and for PCFs was 46 percent (range, 10%-90%). None of the whole blood allogeneic donation informed consents surveyed contained all the common essential or specific blood donation information desired. There is a need for national guidelines for the informed consent process for both the donor and the parent of a minor to ensure adequate information is specified.

Conducting Research in Disease Outbreaks

Conducting Research in Disease Outbreaks

Informed Consent for Clinical Research Involving Patients With Chest Disease in the United States

The concept of informed consent was applied to clinical research in the United States after research abuses were documented in Nazi Germany and this country. The concept is imbedded in the Nuremberg Code, the Declaration of Helsinki, and the Belmont Report. Federal regulations governing clinical research require both the consent of subjects and peer review of research proposals by institutional review boards (IRBs). Subpart A of the Code of Federal Regulations contains basic provisions for the protection of research subjects and requirements for informed consent by subjects or their surrogates; surrogate consent may or may not be allowed under state law. Other subparts contain further protections for subjects with diminished capacity, such as children, that limit the kind of research in which they can participate. Whether these protections should be extended to decisionally impaired adults, including those who are critically ill, remains to be determined. Consent can be deferred or waived for emergency research only rarely in the United States, in contrast to other countries.

Etyczna strona prób klinicznych fazy I w onkologii

The article begins by giving explaining the domination in biomedical experimentation of research leading to the production and implementation of new medicines. The description of these factors serves as an introduction to the fundamental section of the article that discusses the specific features of clinical tests during phase I of oncological therapy. They include above all such elements as the choice of human subjects from among the terminally ill and the non-therapeutic character of the experiments with an accompanying small statistical background of significant effects. The above features are the basic source of ethical dilemmas connected with phase I tests. In the article the following four most important factors have been analyzed: 1. the practical impossibility of obtaining an informed consent of the human subject for participating in the test, 2. the blurring of the border between therapy and experiment, leading to the treatment of phase I experiments as especially valuable though non-cost-effective therapeutic procedures, 3. the blurring of the distinction between a physician-therapist and a physician-researcher, 4. the tendency on the part of physicians and patients to treat phase I experiments as a way to avoid difficult conversations and decisions after all therapeutic options have been exhausted.

Automated consent through privacy agents: Legal requirements and technical architecture

The changes imposed by new information technologies, especially pervasive computing and the Internet, require a deep reflection on the fundamental values underlying privacy and the best way to achieve their protection. The explicit consent of the data subject, which is a cornerstone of most data protection regulations, is a typical example of requirement which is very difficult to put into practice in the new world of “pervasive computing” where many data communications necessarily occur without the users' notice. In this paper, we argue that an architecture based on “Privacy Agents” can make privacy rights protection more effective, provided however that this architecture meets a number of legal requirements to ensure the validity of consent delivered through such Privacy Agents. We first present a legal analysis of consent considering successively (1) its nature; (2) its essential features (qualities and defects) and (3) its formal requirements. Then we draw the lessons of this legal analysis for the design of a valid architecture based on Privacy Agents. To conclude, we suggest an implementation of this architecture proposed in a multidisciplinary project involving lawyers and computer scientists.

Voluntariness of Consent to Research: A Conceptual Model

A good deal of policy and practice in human subjects research aims to ensure that when subjects consent to research, they do so voluntarily. To date, however, voluntariness and its impairment have been poorly conceptualized and studied. The legal doctrine of informed consent could provide a useful model.

The unique challenges of enrolling patients into multiple clinical trials

Multiple interventions are implemented to save the lives of a critically ill patients. The therapeutic value of most of these interventions remains untested. Enrollment of patients in the intensive care unit into multiple studies could improve the efficiency of testing interventions in the intensive care unit. Unfortunately, enrollment of intensive care unit patients into multiple studies is often discouraged. If the same patient is enrolled into more than one study, there is a risk that interactions between interventions could lead to false conclusions. In addition, there is a belief that the families of critically ill patients might feel overly stressed if they are repeatedly approached for consent. This article provides a rationale for enrolling intensive care unit patients into multiple clinical trials. Factorial designs are efficient, but their inherent limitations must be noted. The little evidence that is available shows that most patients would enroll in multiple studies and do not feel overly stressed by participating in more than one study. Modifications to subject consent, data collection, and data analysis for coenrollment could facilitate it. In conclusion, more vigorous promotion of thoughtful coenrollment policies could increase the efficiency of critical care research.

The Holocaust and medical ethics: the voices of the victims

Fifty-nine years ago, Dr Leo Alexander published his now famous report on medicine under the Nazis. In his report he describes the two major crimes of German physicians. The participation...

If no means no, does yes mean yes? Consenting to research intimacies

This article reflects on some ethical dilemmas presented by an ethnographic study of prostitution that I conducted in the 1990s. The study drew one research subject into a long and very close relationship with me, and though she was an active and fully consenting participant in the research, she was also objectified within both the field relationship and the textual products it generated. This kind of contradiction has been recognized and discussed as a more general problem for ethnography by feminist and critical ethnographers. In this article it is considered specifically in relation to informed consent as an ethical issue. If an ethnographer secures the free and informed consent of a research subject, does this necessarily make the intimacy of their subsequent relationship ethical? Is it possible for anyone to genuinely consent to being objectified through the research process?

Banking of Biological Fluids for Studies of Disease-associated Protein Biomarkers

With the increasing demand of providing personalized medicine the need for biobanking of biological material from individual patients has increased. Such samples are essential for molecular research aimed at characterizing diseases at several levels ranging from epidemiology and diagnostic and prognostic classification to prediction of response to therapy. Clinically validated biomarkers may provide information to be used for diagnosis, screening, evaluation of risk/predisposition, assessment of prognosis, monitoring (recurrence of disease), and prediction of response to treatment and as a surrogate response marker. Many types of biological fluids or tissues can be collected and stored in biorepositories. Samples of blood can be further processed into plasma and serum, and tissue pieces can be either frozen or fixed in formalin and then embedded into paraffin. The present review focuses on biological fluids, especially serum and plasma, intended for study of protein biomarkers. In biomarker studies the process from the decision to take a sample from an individual to the moment the sample is safely placed in the biobank consists of several phases including collection of samples, transport of the samples, and handling and storage of samples. Critical points in each step important for high quality biomarker studies are described in this review. Failure to develop and adhere to robust standardized protocols may have significant consequences as the quality of the material stored in the biobank as well as conclusions and clinical recommendations based on analysis of such material may be severely affected.

국내 임상시험에 관한 정보 검색의 현황과 개선방안

This year, the number of approved clinical trials in Korea is expected to exceed approximately 300 cases. In regards to this, the Korea Food & Drug Administration provides statistical data and related laws and guidelines on clinical trials through the Release of clinical trials from its website. However, it is not easy to instantly search the basic information related to the study of design, process, subject's consent form, recruitment of subject, and sponsor's contacts information, etc. Accordingly, the ClinicalTrials.gov that is administered by the National Institutes of Health (NIH) and the Food and Drug Administration (FDA) will be compared against the Release of clinical trial of the Korea Food & Drug Administration in order to identify the proper ways to manage and disclose the clinical trial information to the public.

Substitute Consent for Research Involving the Elderly: A Comparison Between Quebec and France

The authors first describe the rules enacted in Quebec and France to protect adults with decisional impairment who may be approached by investigators to participate in research protocols. They then present two consecutive postal surveys conducted among Quebec and French researchers in aging and designed to (1) assess their knowledge of the legal provisions implemented to protect decisionally incapable adults, (2) elicit their opinions regarding the person best suited to provide substitute consent for research participation, and (3) document their conduct related to obtaining consent for prospective subjects with impaired decisional capacity. Knowledge of the legislation governing substitute consent was poor, even more so among French than Quebec researchers (p < 0.001). In both samples, the majority of respondents felt that the substitute decision-maker does not have to be legally appointed when the study poses little risk to the participant. Practice data revealed a certain discrepancy between the conduct of researchers in aging and the legal provisions regarding consent for research purposes that prevail in their jurisdictions. These findings underscore the need to better educate clinical investigators about existing measures to protect prospective subjects who lack decisional capacity. They also provide some support for allowing close relatives to consent to research participation on behalf of older adults who are unable to consent by themselves and have not been appointed a legal representative.

Sex-related differences in the anteroposterior diameter of the foetal cisterna magna

To measure the anteroposterior diameter of the foetal cisterna magna and observe whether there are differences according to sex. Three hundred and thirty-seven Chinese women with low-risk pregnancies and a singleton foetus between 22 and 38 weeks' gestational age were included in this retrospective study. Informed consent of the volunteer subjects and hospital authority approval were first obtained. Double-blinded for gender, the anteroposterior diameter of the cisterna magna of the foetuses was measured by transabdominal sonography. Magnetic resonance imaging (MRI) was used for those foetuses with mega cisterna magna. All of the foetuses were healthy by prenatal and postnatal examination, including physical and imaging examination. The mean anteroposterior diameter of the cisterna magna of all foetuses was 8.01+/-1.79 mm. The anteroposterior diameter of the cisterna magna had no obvious correlation with the gestational age. The mean anteroposterior diameter of the cisterna magna of 179 male foetuses was 8.63+/-2.16 mm, and the mean anteroposterior diameter of the cisterna magna of 158 female foetuses was 7.87+/-1.74 mm. The size difference was statistically significant (p<0.001). In the 33 foetuses with mega cisterna magna, the number of male foetuses was greater than female foetuses, and the proportion of the foetuses with mega cisterna magna in the male group was significantly higher than the foetuses in the female group (p<0.05). Male foetuses had slightly larger anteroposterior diameters of the cisterna magna than female foetuses. The study would be useful for creating normal range values for the cisterna magna of male and female foetuses.

돼지고기가 공장근로자들의 신기능지표와 혈청 생화학치에 미치는 영향

본 연구는 공장 근로자들을 대상으로 작업환경에 대한 지표조사를 실시한 후 일상식이와 돼지고기를 섭취케 하고 신기능과 혈액지표성분에 미치는 영향을 분석하여 돼지고기의 영양학적인 우수성을 규명하고자 수행하였다. 작업환경이 비교적 열악한 남성근로자 45명에게 6주 동안 자신의 일상식이를 유지하면서 돼지고기를 주 2회(회당 150g) 급여한 다음 시험전후 신기능지표와 혈청생화학치를 조사하였다. 시험 종료 후 신기능지표중 NAG활성도는 감소한 반면 ALA농도는 증가한 것으로 나타났다. 혈청지질 중 총콜레스테롤(TC), 고밀도지단백(HDL) 및 저밀도지단백(LDL)-콜레스테롤농도는 차이가 없었고, 중성지방(TG)농도는 통계적으로 유의하게 증가하였다(p<0.005). 돼지고기 섭취는 혈중 아연, 납 및 카드뮴농도를 감소시켰지만 유의성은 없었다. 본 연구에서 시험대상자의 작업환경이 일반 근로자들에 비해 산업적인 오염노출의 위험도가 더 높다는 사실을 감안할 때 일상식이와 함께 돼지고기의 추가적인 급여가 신기능지표중 NAG활성도 저하와 혈중 카드뮴(Cd)농도를 감소시킨 것으로 나타났다. 향후 이와 관련된 보다 정밀하게 통제된 연구가 필요할 것으로 사료되었다. This study was conducted to reveal the effects of pork consumption on the renal and hematochemical indices of workers occupationally exposed to an unclean environment for 6 weeks. Forty-five free-living volunteers were recruited from the workers employed in a car-engine part factory and a leather dyeing company in the Gyeonggi area. Volunteers were to submit a subject consent form prior to the study. They were asked to complete a questionnaire on dietary habits, and blood and urine samples were collected before and after the pork consumption trial. Pork dishes were fed twice weekly (150g per meal) as part of lunch or dinner at the work place. Urine N-Acetyl-<TEX>${\beta}$</TEX>-D-glucosamidase (NAG) levels were reduced after the trial, but total-cholesterol, HDL-and LDL-cholesterol levels did not change. However, triglyceride levels did increase significantly (p<0.005). The Zn, Pb, and Cd concentrations in serum tended to decrease, though without statistical significance. In conclusion, the regular consumption of pork may be beneficial for renal functions, however further research in this area is needed.

The principle of respect for autonomy – Concordant with the experience of oncology physicians and molecular biologists in their daily work?

BackgroundThis article presents results from a qualitative empirical investigation of how Danish oncology physicians and Danish molecular biologists experience the principle of respect for autonomy in their daily work.MethodsThis study is based on 12 semi-structured interviews with three groups of respondents: a group of oncology physicians working in a clinic at a public hospital and two groups of molecular biologists conducting basic research, one group employed at a public university and the other in a private biopharmaceutical company.ResultsWe found that that molecular biologists consider the principle of respect for autonomy as a negative obligation, where the informed consent of patients or research subjects should be respected. Furthermore, molecular biologists believe that very sick patients are constraint by the circumstances to a certain choice. However, in contrast to molecular biologists, oncology physicians experience the principle of respect for autonomy as a positive obligation, where the physician in dialogue with the patient performs a medical prognosis based on the patient's wishes and ideas, mutual understanding and respect. Oncology physicians believe that they have a positive obligation to adjust to the level of the patient when providing information making sure that the patient understands. Oncology physicians experience situations where the principle of respect for autonomy does not apply because the patient is in a difficult situation.ConclusionIn this study we explore the moral views and attitudes of oncology physicians and molecular biologists and compare these views with bioethical theories of the American bioethicists Tom L. Beauchamp & James F. Childress and the Danish philosophers Jakob Rendtorff & Peter Kemp. This study shows that essential parts of the two bioethical theories are reflected in the daily work of Danish oncology physicians and Danish molecular biologists. However, the study also explores dimensions where the theories can be developed further to be concordant with biomedical practice. The hope is that this study enhances the understanding of the principle of respect for autonomy and the way it is practiced.

Beyond informed consent: the therapeutic misconception and trust

The therapeutic misconception has been seen as presenting an ethical problem because failure to distinguish the aims of research participation from those receiving ordinary treatment may seriously undermine the informed...

Tipping Point, Over the Top, or Just Noncompliance as Usual?

As soon as I read the headline, I thought, here we go again. As a former director of the Office for Human Research Protections at the Department of Health and Human Services, I was hardly surprised when several colleagues sent me the op-ed by Atul Gawande in the New York Times last December called A Lifesaving Checklist. (1) Dr. Gawande, a surgeon at Brigham and Women's Hospital in Boston and staff writer at the New Yorker, suggested that the federal agency responsible for protection of human subjects in research had gone too far--over the bureaucratic edge. Perhaps he was right, but his representation of the facts was not, as OHRP was quick to point out in a statement of its own. (2) OHRP's statement did not evoke the energetic public response that Gawande's did, but then facts have a way of being complicated and nuanced, making drama a bit harder. Gawande's piece and the outcry it provoked gave the impression that OHRP had truly gone over the top--that it had, against all common sense and good judgment, prohibited hospitals and physicians from implementing a simple checklist for inserting a central venous catheter. Getting doctors to follow such a checklist could be a safe and effective quality improvement program that might reduce the incidence of bloodstream infections, which are believed to be caused by poor attention to technique by doctors but have become the eighth leading cause of death in the United States, according to the Centers for Disease Control and Prevention. Gawande's article might also have left the impression that OHRP viewed all efforts to improve quality of care in hospitals as clinical research and had required that they be reviewed and approved by an institutional review board. At least, that seems to be the impression that prompted the chief executive officer of the American Hospital Association, Rich Umberdston, to write an irate letter to Secretary of Health and Human Services Michael Leavitt demanding that OHRP be put in its place and its determinations and statements retracted. The simple truth was that OHRP took no such draconian The lead investigator in the study that sparked this controversy was Peter Pronovost, an anesthesiologist who has dedicated his career to improving safety and quality in medicine. Pronovost is a true believer in quality improvement, but he holds that quality improvement initiatives should be rigorously evaluated to determine whether a specific quality improvement initiative really works. He had proposed a research study to evaluate the effectiveness of the lifesaving checklist, and he had submitted the proposal to the Johns Hopkins institutional review board for review and approval, just as any other properly trained, responsible investigator would. The IRB held that the study was exempt from review because it was a quality improvement program, not human subjects research. This decision prompted a complaint to OHRP that research was being done without prior review and approval and without informed consent of the human subjects who participated in it. OHRP agreed that the project was not exempt from review, forcing the investigators and the institution to take corrective action. The trial was suspended. Gawande--and his readers--were incensed. But when I spoke to Dr. Pronovost, even he agreed that his study was designed to be research, as OHRP understands that term, and that OHRP's determination that IRB review was necessary was consistent with the applicable regulations. While there is room for discussion about risk levels, involvement of human subjects, and requirements for informed consent, the bottom line is that some QI initiatives are research involving human subjects, and that those initiatives are subject to federal regulations and institutional policies for research oversight, whether they turn out to be exempt from IRB review and approval, approvable by expedited review (because they pose no greater than minimal risk), or subject to full IRB review. …

Using Mystery Clients to Assess Condom Negotiation in Malawi: Some Ethical Concerns

To halt the HIV/AIDS epidemic in Malawi, donors supported the government in promoting safer sex among women who solicit sex with men in and around bars. In 1996, a qualitative study explored the changing dynamics of concurrent sexual partnerships, using a variety of researchers and methods. Although most international ethical research codes prescribe the informed consent of research subjects, the present author, as principal investigator for that study, included the mystery-client method, which omits informants' consent. Five trained, pilot-tested, and closely supervised male researchers contacted 101 bar girls and "freelancing" women in trading and urban centers to assess the women's ability to negotiate condom use. The men posed as clients but were instructed not to have sex with their informants. This approach provided important contextualized information to improve HIV transmission-prevention programs, yet it raises ethical concerns. This article is intended to contribute to the dialogue and debate on ethical research involving mystery clients and to encourage other researchers to share their ethical dilemmas and show how they have addressed them.

Communicating with the Elderly: Decision Making and Informed Consent in Subjects with Frailty or Dementia

Obtaining a valid informed consent from an elderly person, especially when frail or with possible dementia, will initially involve the practical problem of assessing the ability to communicate. Only then can the assessment of decisionmaking capacities and the obtaining of informed consent for participation in research be progressed. Normal ageing does not impair communication or decision-making, but pathological status does, this may, or may not, be associated with the ageing process. Perceptual impairment may, in particular, interfere with the communication. Once the subject appreciates and understands that he/she has the right to make a choice then it is important to ensure that he/she fully understands the decision he/she is being asked to make and can communicate and explain in his/her own words why a particular decision was made. In this paper suggestions, based upon existing guidelines or texts, will be made as to how to improve communication with the elderly and the capabilities that the subject must demonstrate to show his capacity to make a decision will be discussed.