Public perception of participation in low-risk clinical trials in critical care using waived consent: a Canadian national survey.

PURPOSE: The acceptability of waiver of consent for participation in clinical research in intensive care unit (ICU) settings is uncertain. We sought to survey the Canadian public to assess levels of support, comfort, and acceptability for waived consent for low-risk clinical trials. METHODS: We performed a prospective cross-sectional survey of the Canadian public aged 18 yr or older. The survey was conducted by Ipsos between 19 and 23 November 2020. The survey content was derived from a literature review and in consultation with a patient and family partnership committee. The survey focused on attitudes and beliefs on waived consent for participation in low-risk clinical trials in ICU settings. The survey contained 35 items focused on sociodemographics, general health status, participation in medical research, and levels of support and comfort with research and with waived consent. The survey used a case study of a low-risk clinical trial intervention in ICU patients. Analysis was descriptive. RESULTS: We included 2,000 participants, 38% of whom reported experience with ICU and 16% with medical research. Participation in medical research was more common among those with postsecondary education, those with chronic disease, and those who were employed in health care. Most (80%) would support a model of waived consent for low-risk clinical trials, citing medical benefits (36%) and low perceived risk (34%). Most (77%) were comfortable with personally participating in a low-risk clinical trial. Most (80%) believed waived consent approaches were acceptable. Half (52%) believed the waived consent process should provide information about the research and include the option of opting out. When asked whether participants should always give full informed consent, regardless of the practicality or level of risk, 74% and 72% agreed, respectively. CONCLUSIONS: There is public support for models of waived consent for participation in low-risk pragmatic clinical trials in ICU settings in Canada; however, this is not universal. This information can inform and guide education, ethics, policy, and legal discussion on consent models.

RéSUMé: OBJECTIF: L'acceptabilité de la renonciation au consentement pour la participation à la recherche clinique à l'unité de soins intensifs (USI) est incertaine. Nous avons cherché à sonder la population canadienne afin d'évaluer les niveaux de soutien, de confort et d'acceptabilité de la renonciation au consentement pour les études cliniques à faible risque. MéTHODE: Nous avons réalisé un sondage transversal prospectif auprès de la population canadienne âgée de 18 ans et plus. Le sondage a été réalisé par Ipsos entre le 19 et le 23 novembre 2020. Le contenu du sondage a été élaboré à partir d'une revue de la littérature et en consultation avec un comité de partenariat composé de patient·es et de familles. Le sondage portait sur les attitudes et les croyances à l'égard de la renonciation au consentement pour participer à des études cliniques à faible risque dans les unités de soins intensifs. Le sondage comportait 35 questions axées sur les données sociodémographiques, l'état de santé général, la participation à la recherche médicale et les niveaux de soutien et de confort à l'égard de la recherche et de la renonciation au consentement. Le sondage s'est appuyé sur une étude de cas d'une intervention d'étude clinique à faible risque chez des patient·es des soins intensifs. L'analyse était descriptive. RéSULTATS: Nous avons inclus 2000 personnes, dont 38 % ont déclaré avoir eu des expériences en soins intensifs et 16 % en recherche médicale. La participation à la recherche médicale était plus fréquente chez les personnes ayant fait des études postsecondaires, celles atteintes de maladies chroniques et celles qui travaillaient dans le domaine des soins de santé. La plupart d'entre elles (80 %) appuieraient un modèle de renonciation au consentement pour les études cliniques à faible risque, citant les avantages médicaux (36 %) et le faible risque perçu (34 %). La majorité des personnes répondantes (77 %) étaient à l'aise à l'idée de participer personnellement à une étude clinique à faible risque. La plupart d'entre elles (80 %) croyaient que les approches fondées sur la renonciation au consentement étaient acceptables. La moitié (52 %) estimaient que le processus de renonciation au consentement devrait fournir des renseignements sur la recherche et inclure la possibilité de se retirer. Lorsqu'on leur a demandé si les participant·es devraient toujours donner un consentement éclairé complet, quel que soit l'aspect pratique ou le niveau de risque, 74 % et 72 % ont répondu par l'affirmative, respectivement. CONCLUSION: Il y a un appui public pour les modèles de renonciation au consentement quant à la participation à des études cliniques pragmatiques à faible risque dans les unités de soins intensifs au Canada; cet appui n'est toutefois pas universel. Ces renseignements peuvent éclairer et orienter l'éducation, l'éthique, les politiques et les discussions juridiques sur les modèles de consentement.

"I think there has to be a mutual respect for there to be value": Evaluating patient engagement in a national clinical trial on de-implementation of low value care.

BACKGROUND: The evaluation of patient engagement in research is understudied and under-reported, making it difficult to know what engagement strategies work best and when. We provide the results of an evaluation of patient engagement in a large Canadian research program focused on the de-implementation of low-value care. We aimed to evaluate the experience and impact of patient engagement in the study. METHODS: An online cross-sectional survey was administered using Microsoft Forms to (1) researchers and study staff and (2) patient partners. The survey was developed following iterative reviews by the project's patient partnership council and evaluation committee. Survey content areas included opinions on patient engagement to date, including challenges to engagement and suggestions for improvement. Patient partners also evaluated the partnership council. Descriptive statistics including counts and percentages described Likert scale survey items, while open comments were analyzed using descriptive content analysis. RESULTS: The survey response rate was 46% (17/37). There were positive attitudes about the value of patient engagement in this project. There was also a high degree of willingness to be involved with patient engagement in future projects, whether as a patient partner or as a researcher including patients on the research team. Most patient partners felt their contributions to the project were valued by researchers and study research staff. Open comments revealed that a co-design approach and full inclusion on the research team were integral to demonstrating the value of patient partner input. Areas for improvement included more frequent and ongoing communication among all team members, as well as earlier training about patient engagement, particularly addressing role expectations and role clarity. CONCLUSIONS: Our data revealed that despite some challenges, team members recognized the value of patient engagement in research and agreed project decisions had been impacted by patient partner input. Ongoing communication was highlighted as an area for improvement, as well as earlier training and ongoing support for all team members, but particularly researchers and study staff. In response to evaluation data, the team has reinstated a quarterly newsletter and plans to use specific patient engagement planning templates across study sites for all project activities. These tools should help make expectations clear for all team members and contribute to a positive patient engagement experience. Findings can inform patient engagement planning and evaluation for other health research projects.

Evaluating patient engagement in research is often not done or not reported, making it hard to know what engagement strategies work best and when. Here, we provide the results of an evaluation of patient engagement in a Canadian Institutes for Health Research (CIHR) Strategy for Patient Oriented Research (SPOR) Innovative Clinical Trial Multi-Year Grant. The project focuses on strategies to reduce two low-value care practices (pre-operative testing in low-risk day surgery and imaging for low back pain). An online survey was sent to project researchers, study staff and patient partners to get their opinions on the patient engagement in the project. Generally, there were positive attitudes about the value of patient engagement in the project. Both patient partners and research study staff were very willing to be involved with patient engagement in future projects. Most patient partners felt their contributions to the project were valued by researchers and study research staff. An important part of showing the value of patient partners was working together to design the project and making sure that the patient partners were considered full members of the research team. Areas for improvement included better communication among all team members and earlier training about patient engagement with a focus on patient roles and expectations. The results from this survey will be used to improve the patient engagement in this project but will also help patient engagement planning and evaluation for other health research projects.

Beyond guideline knowledge: a theory-based qualitative study of low-value preoperative testing.

BACKGROUND: Choosing Wisely Canada and most major anesthesia and preoperative guidelines recommend against obtaining preoperative tests before low-risk procedures. However, these recommendations alone have not reduced low-value test ordering. In this study, the theoretical domains framework (TDF) was used to understand the drivers of preoperative electrocardiogram (ECG) and chest X-ray (CXR) ordering for patients undergoing low-risk surgery ('low-value preoperative testing') among anesthesiologists, internal medicine specialists, nurses, and surgeons. METHODS: Using snowball sampling, preoperative clinicians working in a single health system in Canada were recruited for semi-structured interviews about low-value preoperative testing. The interview guide was developed using the TDF to identify the factors that influence preoperative ECG and CXR ordering. Interview content was deductively coded using TDF domains and specific beliefs were identified by grouping similar utterances. Domain relevance was established based on belief statement frequency, presence of conflicting beliefs, and perceived influence over preoperative test ordering practices. RESULTS: Sixteen clinicians (7 anesthesiologists, 4 internists, 1 nurse, and 4 surgeons) participated. Eight of the 12 TDF domains were identified as the drivers of preoperative test ordering. While most participants agreed that the guidelines were helpful, they also expressed distrust in the evidence behind them (knowledge). Both a lack of clarity about the responsibilities of the specialties involved in the preoperative process and the ease by which any clinician could order, but not cancel tests, were drivers of low-value preoperative test ordering (social/professional role and identity, social influences, belief about capabilities). Additionally, low-value tests could also be ordered by nurses or the surgeon and may be completed before the anesthesia or internal medicine preoperative assessment appointment (environmental context and resources, beliefs about capabilities). Finally, while participants agreed that they did not intend to routinely order low-value tests and understood that these would not benefit patient outcomes, they also reported ordering tests to prevent surgery cancellations and problems during surgery (motivation and goals, beliefs about consequences, social influences). CONCLUSIONS: We identified key factors that anesthesiologists, internists, nurses, and surgeons believe influence preoperative test ordering for patients undergoing low-risk surgeries. These beliefs highlight the need to shift away from knowledge-based interventions and focus instead on understanding local drivers of behaviour and target change at the individual, team, and institutional levels.

Patient-identified priorities for successful partnerships in patient-oriented research.

Albertans4HealthResearch, supported by the Alberta Strategy for Patient-Oriented Research Patient Engagement Team, hosted a virtual round table discussion to develop a list of considerations for successful partnerships in patient-oriented research. The group, which consists of active patient partners across the Canadian province of Alberta and some research staff engaged in patient-oriented research, considered advice for academic researchers on how to best partner with patients and community members on health research projects. The group identified four main themes, aligned with the national strategy for patient-oriented research (SPOR) patient engagement framework, highlighting important considerations for researchers from the patient perspective, providing practical ways to implement SPOR's key principles: inclusiveness, support, mutual respect, and co-building. This commentary considers the process behind this engagement exercise and offers advice directly from active patient research partners on how to fulfill the operational patient engagement mandate. Academic research teams can use this guidance when considering how to work together with patient partners and community members.

Albertans4HealthResearch, supported by the Alberta Strategy for Patient-Oriented Research (AbSPORU) Patient Engagement Team, hosted a virtual round table discussion to develop a list of considerations for successful partnerships in patient-oriented research. The group, which consists of active patient partners across the Canadian province of Alberta and some research staff engaged in patient-oriented research, considered advice for academic researchers on how to best partner with patients and community members on health research projects. The group identified four main themes, aligned with the national Strategy for Patient-Oriented Research (SPOR) Patient Engagement Framework, highlighting important considerations for researchers from the patient perspective, providing practical ways to implement SPOR's key principles: inclusiveness, support, mutual respect, and co-building. This commentary considers the process behind this engagement exercise and offers advice directly from active patient research partners on how to fulfill the operational patient engagement mandate. Academic research teams can use this guidance when considering how to work together with patient partners and community members.

Michigan BioTrust for Health: public support for using residual dried blood spot samples for health research.

PURPOSE: Focus groups were utilized as a mechanism to solicit input from the public in developing the Michigan BioTrust for Health, a program of the Michigan Department of Community Health to improve storage conditions and promote use of residual newborn screening dried blood spots in health research. METHODS: In 2008-2009, 10 diverse communities representative of the general public that might have special concerns as stakeholders in the BioTrust were identified, and 4 discussion questions were developed for use with a standard agenda. Focus group discussions were audio-recorded and transcribed by department staff. Qualitative conclusions resulting from the group discussions were compared with written, quantitative pre- and post-survey responses completed by individual participants. RESULTS: Overall, there was considerable concurrence of opinion across the focus groups. Participants were generally positive about the BioTrust; a sentiment that held true across different demographic populations with over 85% of participants stating they would support use of residual dried blood spots in health research. CONCLUSION: The focus group process and findings played an important role for public health policy makers in affirming the importance of engaging and informing the public and led to concrete steps to foster community support.

Using core public health functions to promote BRCA best practices among health plans.

OBJECTIVE: The Michigan Department of Community Health (MDCH) Cancer Genomics Program sought to increase the number of health plans with a written policy aligned with the United States Preventive Services Task Force (USPSTF) Grade B Recommendation stating that women whose family history is associated with an increased risk for deleterious mutations in BRCA1 or BRCA2 be referred for genetic counseling and evaluation for BRCA testing. METHODS: Through a cooperative agreement with the Centers for Disease Control and Prevention, MDCH with health plan partners utilized multiple methods (i.e. surveillance, education, federal and state policies, partnerships, and dissemination) to increase the number of health plans with a written policy aligned with the USPSTF Grade B BRCA Recommendation between 2008 and 2011. RESULTS: Since 2008, the number of health plans that have policies consistent with USPSTF Grade B BRCA Recommendation in Michigan increased from 4 to 11. These 11 health plans provide coverage to over 7 million Michigan residents. Honors were bestowed by MDCH to these 11 health plans for their exemplary written policies. CONCLUSIONS: MDCH has implemented a novel and effective approach to promote cancer genomics best practices through health plan policies that serves as a model for federal and state agencies.

Public support for the use of newborn screening dried blood spots in health research.

OBJECTIVES: The level of support among Michigan adults for the use of residual newborn screening dried blood spots (DBS) was investigated. METHODS: We analyzed data from 4 questions on the 2008 Michigan Behavioral Risk Factor Surveillance System (n = 3,108). The questions asked about general support for the use of DBS for research and for research investigating childhood diseases, adult diseases and diseases related to environmental exposures. RESULTS: The majority of adults (72.3%) favored the use of DBS for research intended to benefit the health of residents. With more question specificity, a higher proportion of adults (84.2%-86.8%) were found to favor the use of DBS for research, and a lower proportion had no opinion. The odds of favoring use were higher among those who were younger, female, white, healthy, or with at least a high school degree. CONCLUSIONS: This is the first population survey of adult attitudes regarding use of DBS for different types of health research, with results showing considerable public support. The findings are being used in community outreach efforts and highlight the need to investigate opposition in vulnerable populations.

Recommendations for Telephone Counseling.

Telephone counseling can provide a convenient, accessible, and valuable source of information to the general public, health care providers, and other professionals. In the genetic counseling profession, telephone counseling is often associated with teratogen information services. However, genetic counselors routinely utilize the telephone in a number of different counseling encounters. Nevertheless, the literature provides very little guidance to how that encounter might be conducted, what information should be obtained and provided, or how the encounter should be documented. We present a brief overview of the history of telephone counseling, a description of the major differences between telephone counseling and a face-to-face counseling session, and a framework to optimize a telephone counseling session.

Modulation of B12 dosage and response in fetal treatment of methylmalonic aciduria (MMA): titration of treatment dose to serum and urine MMA.

OBJECTIVE: Prenatally diagnosed methylmalonic aciduria (MMA) has been treated in only a few fetuses, and has been done empirically with maternally administered cyanocobalamin (B12) in attempts to ameliorate sequelae that include failure to thrive, developmental delay, dehydration, and coma. There has not been a systematic attempt to titrate doses to fetal response. We investigated the alterations in maternal dosage necessary to keep maternal plasma (MP) and urine (MU) levels of MMA in the normal range secondary to the ability of pharmacological doses of B12 to catalyze the reaction of methylmalonyl-coenzyme A to succinyl-coenzyme A. METHODS: A 28-year-old woman, with a 3-year-old son affected with MMA, underwent amniocentesis at 15 weeks which showed a normal karyotype, elevated amniotic fluid MMA, and decreased amniocyte 5'-deoxyadenosylcobalamin, propionate, and methyl-tetrahydrofolate. MP and MU MMA levels were measured biweekly. B12 doses were altered periodically according to laboratory-determined levels. RESULTS: MP and MU levels varied with gestational age and in response to increases in maternally administered B12. CONCLUSIONS: With increasing gestation, fetal, and placental size, increasing doses of B12 are necessary to maintain MP and MU levels of MMA within normal range. The data suggest that close surveillance and frequent measurements of MMA are necessary to properly titrate B12 treatment.

Prenatal diagnosis of fetal herpes simplex infection.

BACKGROUND: Intrauterine infection with herpes simplex virus (HSV) has been associated with a significant number of neonatal HSV infections. When these infections begin in utero, the associated morbidity is more severe, and treatment regimens may be less effective. CASE: A 24-year-old nullipara with an abnormal triple screen and multiple ultrasound abnormalities at 19 weeks' gestation underwent amniocentesis and cordocentesis. Laboratory results were consistent with HSV infection. The patient elected to terminate the pregnancy, and on postmortem examination of the fetus, evidence of disseminated disease was present. CONCLUSION: We believe that this case documents a relationship between HSV infection and findings on ultrasound that have previously been described in association with other in utero infections. We suggest that general viral cultures of the amniotic fluid be done when in utero infection is suspected.

Parental decisions to terminate/continue following abnormal cytogenetic prenatal diagnosis: "what" is still more important than "when".

This study was undertaken to determine if parental decisions to continue or terminate following the diagnosis of a cytogenetic abnormality have changed over the past 8 years at the same center. Parental decisions in 310 prenatal chromosomal abnormalities were stratified by procedure (chorionic villus sampling [CVS] vs. amniocentesis) and the severity of the anomaly (severe vs mild-moderate). Patients with severe anomalies were much more likely to terminate regardless of gestational age. There was a trend (P = .107) toward a lower rate of termination for mild-moderate degrees in the second trimester. There was no change in patient's decisions over time. Patients' decisions about termination are focused on the severity of the disorder and only marginally influenced by when in gestation the decision is made.

Impact of abnormal second-trimester maternal serum single, double, and triple screening on patient choices about prenatal diagnosis.

The development of multiple-marker biochemical screening has increased the percentage of aneuploidies detected for all age groups and has also increased the abnormality/amniocentesis ratio from about 1 in 85 for maternal serum alpha-fetoprotein alone (single screening) to about 1 in 50 for either maternal serum alpha-fetoprotein plus human chorionic gonadotropin (double screening) or maternal serum alpha-fetoprotein combined with human chorionic gonadotropin and unconjugated estriol (triple screening). We evaluated the decisions to have or decline amniocentesis of 985 patients 'at risk' by either single, double, or triple screening, as multiple markers were phased in over a 3-year period. The patient acceptance of the procedure did not change (approximately 80%) either by actual risk or type of biochemical screening. The labeling of 'at risk' status is more important than actual numerical risks, and the patient perception of risk status must be considered in counseling.

Pregnancy outcome when both members of a couple have balanced translocations.

BACKGROUND: Couples in which one partner is the carrier of a balanced translocation have increased risks of infertility, recurrent abortion, and delivery of chromosomally abnormal offspring. Pregnancies in which both partners carry balanced translocations are uncommon; therefore, only limited information regarding risk figures is available. We present a couple in which both members had a balanced translocation and discuss their pregnancy outcomes. CASE: A couple had three first-trimester spontaneous abortions at 12, 10, and 8 weeks' gestation, respectively. Both partners were found to be carriers of balanced autosomal translocations. The mother had a Robertsonian translocation with the karyotype 45,XX,t(13q14q). The father had a reciprocal translocation with a 46,XY,t(1;4)(q32;q25) karyotype. There was no information regarding the karyotype of the patient's first-born child with a previous partner. The patient's first-born child with her current partner carried a double balanced translocation karyotype of 45,XX,t(13;14)t(1;4). Their second and third children both had a 45,XX,t(13q14q) karyotype. CONCLUSION: Couples in which both members have a balanced translocation are at increased risk for adverse pregnancy and fetal outcomes, but precise information regarding risk estimates for this rare circumstance is limited. Genetic counseling of such couples therefore presents a unique challenge.

Secretion of a novel T-lymphocyte cytokine possessing both chemotactic and growth factor activity by serotonin-stimulated human aortic endothelial cells.

The development of an extralymphatic T-lymphocyte focus of inflammation requires chemoattractant-induced cell migration and growth factor-induced cell proliferation. In a previous study, we identified a novel 13- to 15-kDa T-lymphocyte-specific chemotactic cytokine, endothelial cell-derived lymphocyte chemoattractant activity (ED-LCA), secreted by serotonin-stimulated human aortic endothelial cells. Based on its physicochemical and functional characteristics and antibody inhibition studies, ED-LCA is distinct from previously identified endothelial cell-derived IL-1, IL-6, and IL-8. Because of the association between T-lymphocyte chemotactic and growth factor activity, in the current study, we investigated the effect of ED-LCA on T cell growth by assessing its capacity to induce markers of the passage of T cells from the resting (G0) state into the G1 phase of the cell cycle, such as receptors for IL-2 (IL-2R) and transferrin (TFR), and class II major histocompatibility complex antigens (HLA-DR). Incubation of G0 freshly isolated human T lymphocytes for 48 h with chromatographically resolved, partially purified ED-LCA resulted in a threefold increase in expression of IL-2R, a threefold increase in TFR, and a twofold increase in HLA-DR. Double antibody labeling demonstrated that IL-2R was induced in both CD4+ and CD8+ T cell subsets. Although incubation of human T cells with ED-LCA alone did not induce DNA synthesis, addition of exogenous IL-2 to T cells pulsed with ED-LCA for 24 h caused an increase in DNA synthesis with a stimulation index of 3.5. By up-regulating functional cell surface receptors for IL-2 on T lymphocytes and priming them to respond to exogenous IL-2, ED-LCA is a competence growth factor. By virtue of its effect on T cells, as a chemotactic and competence factor, this endothelial cell-derived mitoattractant could participate with other T-cell growth factors like IL-2 in the generation of an extralymphatic T-lymphocyte inflammatory response.

Using lay volunteers to represent children in child protection court proceedings.

Despite a widespread conviction that children ought to be independently represented in child protection court proceedings in the United States, there is little consensus as to what the role of that independent child advocate ought to be or, indeed, who should fulfill that role. This study accomplished three purposes: articulated an aggressive, ambitious and continuous role for the child's representative which encompassed a broad range of the child's interests, both legal and nonlegal; provided training in this role to demonstration groups of attorneys, law students and lay volunteers; and compared the effectiveness of each of the three demonstration groups in representing children to one another and to a control group of attorneys who received no special training from the research team. The findings indicate that carefully selected and trained lay people representing children in child abuse and neglect legal proceedings under lawyer supervision performed similarly to trained lawyers and law students in the way they approached their duties and in case outcomes achieved and significantly different from attorneys who, consistent with the practice in nearly all the United States, received no special training in child advocacy.