Patient perspectives on pharmacogenomic (PGx) testing for antidepressant prescribing in primary care: a qualitative description study.

Many patients with major depressive disorder (MDD) try multiple antidepressants before finding one that works well and is tolerable. Pharmacogenomic (PGx) testing was developed to facilitate more efficacious prescribing. This technology has not been robustly implemented clinically. Patient perspectives are critical to policy decisions, but the views of patients with MDD about the use of PGx testing to guide antidepressant prescribing have not been extensively examined, particularly in publicly funded healthcare systems. The purpose of this qualitative description study was to produce actionable patient perspectives evidence to inform future technology assessment of PGx testing. We conducted semi-structured interviews with 21 adults with MDD for which antidepressants were indicated in Ontario, Canada, and used the Ontario Decision Determinants Framework to conduct an unconstrained deductive content analysis. Patients expressed views about the overall clinical benefit of PGx testing in depression care, preferences for deployment of testing, perspectives on ethical considerations, opinions about equity and patient care, and beliefs regarding the feasibility of adopting PGx testing into the healthcare system. They also worried about the possibility of conflicts of interest between PGx test manufacturers and pharmaceutical companies. This study provides policymakers with patient priorities to facilitate the development of patient-centred policies. It highlights that formal adoption of PGx testing into the healthcare system requires a focus on equity of access and health outcomes.

Primary care provider interventions for addressing cancer screening participation with marginalised patients: a scoping review protocol.

INTRODUCTION: Cancer screening is an integral component of primary care, and providers can play a key role in facilitating screening. While much work has focused on patient interventions, there has been less attention on primary care provider (PCP) interventions. In addition, marginalised patients experience disparities in cancer screening which are likely to worsen if not addressed. The objective of this scoping review is to report on the range, extent and nature of PCP interventions that maximise cancer screening participation among marginalised patients. Our review will target cancers where there is strong evidence to support screening, including lung, cervical, breast and colorectal cancers. METHODS AND ANALYSIS: This is a scoping review conducted in accordance with the framework by Levac et al. Comprehensive searches will be conducted by a health sciences librarian using Ovid MEDLINE, Ovid Embase, Scopus, CINAHL Complete and the Cochrane Central Register of Controlled Trials. We will include peer-reviewed English language literature published from 1 January 2000 to 31 March 2022 that describes PCP interventions to maximise cancer screening participation for breast, cervical, lung and colorectal cancers. Two independent reviewers will screen all articles and identify eligible studies for inclusion in two stages: title and abstract, then full text. A third reviewer will resolve any discrepancies. Charted data will be synthesised through a narrative synthesis using a piloted data extraction form informed by the Template for Intervention Description and Replication checklist. ETHICS AND DISSEMINATION: Since this is a synthesis of digitally published literature, no ethics approval is needed for this work. We will target appropriate primary care or cancer screening journals and conference presentations to publish and disseminate the results of this scoping review. The results will also be used to inform an ongoing research study developing PCP interventions for addressing cancer screening with marginalised patients.

Considerations for developing regulations for direct-to-consumer genetic testing: a scoping review using the 3-I framework.

Direct-to-consumer (DTC) genetic testing exists largely outside of any regulatory schemes, and studies providing a comprehensive overview of the ethical, social, legal, and technological considerations for regulating these types of technologies are lacking. This paper uses the 3-I framework for policy analysis to analyze the ideas, interests, and institutions relevant to policy development for DTC genetic testing in North America and internationally. A scoping review was conducted. Citation databases were searched for papers addressing the ethical, social, legal, and technological implications of DTC genetic testing; stakeholder perspectives on and experiences with DTC genetic testing; or the effect of such testing on the healthcare system. Ninety-nine publications, organizational reports, governmental documents, or pieces of legislation were included. The ideas included are autonomy, informed decision making, privacy, and clinical validity and utility. The interests discussed are those of the public and healthcare providers. The institutions included are regulatory organizations such as the Food and Drug Administration in the United States, laws governing the implementation or delivery of genetic testing in general, and legislation created to protect against genetic discrimination. This analysis clarifies the ethical, social, legal, and technological issues of DTC genetic testing regulation. This information can be used by policy makers to develop or strengthen regulations for DTC genetic testing such as requiring an assessment of the clinical validity of tests before they become publicly available, controlling how tests are marketed, and stipulating requirements for healthcare provider involvement and informed consent.

Immediate versus delayed sequential bilateral cataract surgery in children: a cost-effectiveness analysis.

BACKGROUND/AIMS: Children with bilateral cataracts may undergo immediate sequential bilateral cataract surgery (ISBCS), which involves surgery on both eyes during the same general anaesthesia, or delayed sequential bilateral cataract surgery (DSBCS), which involves operating on each eye on separate days and requires a second anaesthesia. ISBCS is viewed with caution because of the risk of bilateral endophthalmitis. Proponents of ISBCS emphasise that the incidence of serious complications is low and is outweighed by benefits such as avoidance of multiple anaesthesia, faster visual rehabilitation and potential for decreased costs. However, there is a paucity of literature regarding the cost-effectiveness of ISBCS in children. We conducted a cost-effectiveness analysis to determine whether ISBCS is more cost-effective than DSBCS from the societal and health system perspectives in Ontario, Canada, which has a universal, single-payer system. METHODS: A retrospective analysis of children who underwent ISBCS or DSBCS at a tertiary referral paediatric hospital was conducted. A decision tree was constructed using TreeAge Pro 2018 software. Clear visual axis was the measure of effectiveness. A time horizon of 8 weeks postoperatively was adopted. Both direct and indirect costs were included. RESULTS: Fifty-three children were included, 37 in the ISBCS group and 16 in the DSBCS group. ISBCS and DSBCS were equally effective. ISBCS resulted in cost-savings of $3,776 (95% CI:-$4,641 to $12,578) CAD, per patient, from the societal perspective and $2,200 (95% CI:-$5,615 to $10,373) CAD per patient from the health system perspective. CONCLUSION: ISBCS was less costly than DSBCS from both societal and health system perspectives while being equally effective.

Cascade health service use in family members following genetic testing in children: a scoping literature review.

Cascade genetic testing is the identification of individuals at risk for a hereditary condition by genetic testing in relatives of people known to possess particular genetic variants. Cascade testing has health system implications, however cascade costs and health effects are not considered in health technology assessments (HTAs) that focus on costs and health consequences in individual patients. Cascade health service use must be better understood to be incorporated in HTA of emerging genetic tests for children. The purpose of this review was to characterise published research related to patterns and costs of cascade health service use by relatives of children with any condition diagnosed through genetic testing. To this end, a scoping literature review was conducted. Citation databases were searched for English-language papers reporting uptake, costs, downstream health service use, or cost-effectiveness of cascade investigations of relatives of children who receive a genetic diagnosis. Included publications were critically appraised, and findings were synthesised. Twenty publications were included. Sixteen had a paediatric proband population; four had a combined paediatric and adult proband population. Uptake of cascade testing varied across diseases, from 37% for cystic fibrosis, 39% to 65% for hypertrophic cardiomyopathy, and 90% for rare monogenic conditions. Two studies evaluated costs. It was concluded that cascade testing in the child-to-parent direction has been reported in a variety of diseases, and that understanding the scope of cascade testing will aid in the design and conduct of HTA of emerging genetic technologies to better inform funding and policy decisions.

Incorporating Cascade Effects of Genetic Testing in Economic Evaluation: A Scoping Review of Methodological Challenges.

Cascade genetic testing is indicated for family members of individuals testing positive on a genetic test, and is particularly relevant for child health because of their vulnerability and the long-term health and economic implications. Cascade testing has patient- and health system-level implications; however cascade costs and health effects are not routinely considered in economic evaluation. The methodological challenges associated with incorporating cascade effects in economic evaluation require examination. The purpose of this scoping review was to identify published economic evaluations that considered cascade genetic testing. Citation databases were searched for English-language economic evaluations reporting on cascade genetic testing. Nineteen publications were included. In four, genetic testing was used to identify new index patients-cascade effects were also considered; thirteen assessed cascade genetic testing strategies for the identification of at-risk relatives; and two calculated the costs of cascade genetic testing as a secondary objective. Methodological challenges associated with incorporating cascade effects in economic evaluation are related to study design, costing, measurement and valuation of health outcomes, and modeling. As health economic studies may currently be underestimating both the cost and health benefits attributable to genetic technologies through omission of cascade effects, development of methods to address these difficulties is required.

Implementing Publicly Funded Noninvasive Prenatal Testing for Fetal Aneuploidy in Ontario, Canada: Clinician Experiences With a Disruptive Technology.

The last decade has experienced unprecedented uptake of noninvasive prenatal testing (NIPT), creating significant changes in the way prenatal clinicians provide services. Through the lens of social shaping of technology, we examine the effects of the introduction of this technology on the health care system in Ontario, Canada. Using a qualitative descriptive approach, we conducted a cross-sectional study investigating clinicians' perspectives of NIPT in 2014, 2016, and 2018. Through in-depth interviews (n = 37), we explored their perspectives on the impact of NIPT on their referral practices, workload, coordination of testing modalities, education and counseling, and elicited their views on recent expansions of the test. Findings suggest that the introduction of NIPT has created unintended consequences with respect to clinician workload and wellness, clinician education, equity of access, and public system resources. Responsiveness from decision makers is key to ensuring the responsible use of NIPT in the health care system.

Perspectives of Pregnant People and Clinicians on Noninvasive Prenatal Testing: A Systematic Review and Qualitative Meta-synthesis.

Background: Pregnant people have a risk of carrying a fetus affected by a chromosomal anomaly. Prenatal screening is offered to pregnant people to assess their risk. In recent years, noninvasive prenatal testing (NIPT) has been introduced clinically, which uses the presence of circulating cell-free fetal DNA in the maternal blood to quantify the risk of a chromosomal anomaly. At present, NIPT is publicly funded for pregnancies at high risk of a chromosomal anomaly, and available to pregnant people at average risk if they choose to pay out of pocket. Methods: We performed a systematic review of primary, empirical qualitative research that describes the experiences and perspectives of pregnant people, their families, clinicians, and others with lived experience relevant to NIPT. We were interested in the beliefs, experiences, preferences, and perspectives of these groups. We analyzed the evidence available in 36 qualitative and mixed-methods studies using the integrative technique of qualitative meta-synthesis. Results: Most people (pregnant people, clinicians, and others with relevant lived experience) said that NIPT offered important information to pregnant people and their partners. Most people were very enthusiastic about widening access to NIPT because it can provide information about chromosomal anomalies quite early in pregnancy, with relatively high accuracy, and without risk of procedure-related pregnancy loss. However, many groups cautioned that widening access to NIPT may result in routinization of this test, causing potential harm to pregnant people, their families, the health care system, people living with disabilities, and society as a whole. Widened logistical, financial, emotional, and informational access may be perceived as a benefit, but it can also confer harm on various groups. Many of these challenges echo historical critiques of other forms of prenatal testing, with some issues mitigated or exacerbated by the particular features of NIPT. Conclusions: Noninvasive prenatal testing offers significant benefit for pregnant people but may also be associated with potential harms related to informed decision-making, inequitable use, social pressure to test, and reduced support for people with disabilities.

Facilitating informed choice about non-invasive prenatal testing (NIPT): a systematic review and qualitative meta-synthesis of women's experiences.

BACKGROUND: Non-invasive prenatal testing (NIPT) can be used to accurately detect fetal chromosomal anomalies early in pregnancy by assessing cell-free fetal DNA present in maternal blood. The rapid diffusion of NIPT, as well as the ease and simplicity of the test raises concerns around informed decision-making and the potential for routinization. Introducing NIPT in a way that facilitates informed and autonomous decisions is imperative to the ethical application of this technology. We approach this imperative by systematically reviewing and synthesizing primary qualitative research on women's experiences with and preferences for informed decision-making around NIPT. METHODS: We searched multiple bibliographic databases including Ovid MEDLINE, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), and ISI Web of Science Social Sciences Citation Index (SSCI). Our review was guided by integrative qualitative meta-synthesis, and we used a staged coding process similar to that of grounded theory to conduct our analysis. RESULTS: Thirty empirical primary qualitative research studies were eligible for inclusion. Women preferred to learn about NIPT from their clinicians, but they expressed dissatisfaction with the quality and quantity of information provided during counselling and often sought information from a variety of other sources. Women generally had a good understanding of test characteristics, and the factors of accuracy, physical risk, and test timing were the critical information elements that they used to make informed decisions around NIPT. Women often described NIPT as easy or just another blood test, highlighting threats to informed decision-making such as routinization or a pressure to test. CONCLUSIONS: Women's unique circumstances modulate the information that they value and require most in the context of making an informed decision. Widened availability of trustworthy information about NIPT as well as careful attention to the facilitation of counselling may help facilitate informed decision-making. TRIAL REGISTRATION: PROSPERO 2018 CRD42018086261 .

Women's perspectives on the ethical implications of non-invasive prenatal testing: a qualitative analysis to inform health policy decisions.

BACKGROUND: Non-Invasive Prenatal Testing (NIPT) is a technology which provides information about fetal genetic characteristics (including sex) very early in pregnancy by examining fetal DNA obtained from a sample of maternal blood. NIPT is a morally complex technology that has advanced quickly to market with a strong push from industry developers, leaving many areas of uncertainty still to be resolved, and creating a strong need for health policy that reflects women's social and ethical values. We approach the need for ethical policy-making by studying the use of NIPT and emerging policy in the province of Ontario, Canada. METHODS: Using an adapted version of constructivist grounded theory, we conducted interviews with 38 women who have had personal experiences with NIPT. We used an iterative process of data collection and analysis and a staged coding strategy to conduct a descriptive analysis of ethics issues identified implicitly and explicitly by women who have been affected by this technology. RESULTS: The findings of this paper focus on current ethical issues for women seeking NIPT, including place in the prenatal pathway, health care provider counselling about the test, industry influence on the diffusion of NIPT, consequences of availability of test results. Other issues gain relevance in the context of future policy decisions regarding NIPT, including funding of NIPT and principles that may govern the expansion of the scope of NIPT. These findings are not an exhaustive list of all the potential ethical issues related to NIPT, but rather a representation of the issues which concern women who have personal experience with this test. CONCLUSIONS: Women who have had personal experience with NIPT have concerns and priorities which sometimes contrast dramatically with the theoretical ethics literature. These findings suggest the importance of engaging patients in ethical deliberation about morally complex technologies, and point to the need for more deliberative patient engagement work in this area.