A scoping review establishes need for consensus guidance on reporting health equity in observational studies.

OBJECTIVES: To evaluate the support from the available guidance on reporting of health equity in research for our candidate items and to identify additional items for the Strengthening Reporting of Observational studies in Epidemiology-Equity extension. STUDY DESIGN AND SETTING: We conducted a scoping review by searching Embase, MEDLINE, CINAHL, Cochrane Methodology Register, LILACS, and Caribbean Center on Health Sciences Information up to January 2022. We also searched reference lists and gray literature for additional resources. We included guidance and assessments (hereafter termed "resources") related to conduct and/or reporting for any type of health research with or about people experiencing health inequity. RESULTS: We included 34 resources, which supported one or more candidate items or contributed to new items about health equity reporting in observational research. Each candidate item was supported by a median of six (range: 1-15) resources. In addition, 12 resources suggested 13 new items, such as "report the background of investigators". CONCLUSION: Existing resources for reporting health equity in observational studies aligned with our interim checklist of candidate items. We also identified additional items that will be considered in the development of a consensus-based and evidence-based guideline for reporting health equity in observational studies.

How We Might Further Integrate Considerations of Environmental Impact When Assessing the Value of Health Technologies.

There is growing awareness of the impact health technologies can have on the environment and the negative consequences of these environmental impacts on human health. However, health system decision-makers may lack the expertise, data, or resources to incorporate environmental considerations when making decisions about the adoption and use of health technologies. In this article, we describe how health technology assessment (HTA) is evolving to address climate change by providing health system decision-makers with the information they can use to reduce the impact of health care systems on the environment. Our objective is to consider approaches for including the environment domain when conducting an HTA-in particular, the use of the deliberative process-and for determining when the domain should be included. We explore the challenges of gathering the relevant data necessary to assess the environmental impact of a health technology, and we describe a "triage" approach for determining when an in-depth environmental impact assessment is warranted. We also summarize related initiatives from HTA agencies around the world.

Guidance on review type selection for health technology assessments: key factors and considerations for deciding when to conduct a de novo systematic review, an update of a systematic review, or an overview of systematic reviews.

BACKGROUND: A systematic review (SR) helps us make sense of a body of research while minimizing bias and is routinely conducted to evaluate intervention effects in a health technology assessment (HTA). In addition to the traditional de novo SR, which combines the results of multiple primary studies, there are alternative review types that use systematic methods and leverage existing SRs, namely updates of SRs and overviews of SRs. This paper shares guidance that can be used to select the most appropriate review type to conduct when evaluating intervention effects in an HTA, with a goal to leverage existing SRs and reduce research waste where possible. PROCESS: We identified key factors and considerations that can inform the process of deciding to conduct one review type over the others to answer a research question and organized them into guidance comprising a summary and a corresponding flowchart. This work consisted of three steps. First, a guidance document was drafted by methodologists from two Canadian HTA agencies based on their experience. Next, the draft guidance was supplemented with a literature review. Lastly, broader feedback from HTA researchers across Canada was sought and incorporated into the final guidance. INSIGHTS: Nine key factors and six considerations were identified to help reviewers select the most appropriate review type to conduct. These fell into one of two categories: the evidentiary needs of the planned review (i.e., to understand the scope, objective, and analytic approach required for the review) and the state of the existing literature (i.e., to know the available literature in terms of its relevance, quality, comprehensiveness, currency, and findings). The accompanying flowchart, which can be used as a decision tool, demonstrates the interdependency between many of the key factors and considerations and aims to balance the potential benefits and challenges of leveraging existing SRs instead of primary study reports. CONCLUSIONS: Selecting the most appropriate review type to conduct when evaluating intervention effects in an HTA requires a myriad of factors to be considered. We hope this guidance adds clarity to the many competing considerations when deciding which review type to conduct and facilitates that decision-making process.

Rapid qualitative evidence syntheses (rQES) in health technology assessment: experiences, challenges, and lessons.

Healthcare decision makers are increasingly demanding that health technology assessment (HTA) is patient focused, and considers data about patients' perspectives on and experiences with health technologies in their everyday lives. Related data are typically generated through qualitative research, and in HTA the typical approach is to synthesize primary qualitative research through the conduct of qualitative evidence synthesis (QES). Abbreviated HTA timelines often do not allow for the full 6-12 months it may take to complete a QES, which has prompted the Canadian Agency for Drugs and Technologies in Health (CADTH) to explore the concept of "rapid qualitative evidence synthesis" (rQES). In this paper, we describe our experiences conducting three rQES at CADTH, and reflect on challenges faced, successes, and lessons learned. Given limited methodological guidance to guide this work, our aim is to provide insight for researchers who may contemplate rQES. We suggest several lessons, including strategies to iteratively develop research questions and search for eligible studies, use search of filters and limits, and use of a single reviewer experienced in qualitative research throughout the review process. We acknowledge that there is room for debate, though believe rQES is a laudable goal and that it is possible to produce a quality, relevant, and useful product, even under restricted timelines. That said, it is vital to recognize what is lost in the name of rapidity. We intend our paper to advance the necessary debate about when rQES may be appropriate, and not, and enable productive discussions around methodological development.

USING THE INTEGRATE-HTA GUIDANCE: EXPERIENCE FROM CADTH.

OBJECTIVES: The aim of this study was to describe an initial exploration by CADTH, Canada's pan-Canadian health technology assessment (HTA) agency, in using the INTEGRATE-HTA guidance in the production of an HTA that examined the use of both in-center and in-home dialysis modalities for the treatment of end-stage kidney disease in adults in Canada. METHODS AND RESULTS: We outline CADTH's standard HTA production process and context and then describe the experience of the assessment team in using the INTEGRATE-HTA guidance, specifically to help structure and guide the use of a logic model, the identification of implementation issues, and the identification and examination of ethical issues. For each of the aspects, we describe and reflect on how the assessment team used the guidance, challenges that were encountered in its use, and whether and how we might address these challenges when using the INTEGRATE-HTA guidance in the future. CONCLUSIONS: INTEGRATE-HTA provided detailed and helpful guidance for truly integrating wide-ranging aspects of HTA. Our agency was challenged by a steep learning curve for assessment team members, tight project timelines, and a misalignment of current HTA processes with those required to implement the guidance. Nevertheless, using the guidance initiated a dialogue about what might be needed to assess complex interventions and the potential process changes that could facilitate conducting more integrated assessments.

EVALUATION OF PATIENT AND PUBLIC INVOLVEMENT INITIATIVES IN HEALTH TECHNOLOGY ASSESSMENT: A SURVEY OF INTERNATIONAL AGENCIES.

OBJECTIVES: Although there is increased awareness of patient and public involvement (PPI) among health technology assessment (HTA) organizations, evaluations of PPI initiatives are relatively scarce. Our objective as members of Health Technology Assessment International's (HTAi's) Patient and Citizen Involvement Group (PCIG) was to advance understanding of the range of evaluation strategies adopted by HTA organizations and their potential usefulness. METHODS: In March 2016, a survey was sent to fifty-four HTA organizations through the International Network of Agencies for Health Technology Assessment (INAHTA) and contacts of members of HTAi's PCIG. Respondents were asked about their organizational structure; how patients and members of the public are involved; whether and how PPI initiatives have been evaluated, and, if so, which facilitators and challenges to evaluation were found and how results were used and disseminated. RESULTS: Fifteen (n = 15) programs from twelve countries responded (response rate 27.8 percent) that involved patients (14/15) and members of the public (10/15) in HTA activities. Seven programs evaluated their PPI activities, including participant satisfaction (5/7), process (5/7) and impact evaluations (4/7). Evaluation results were used to improve PPI activities, identify education and training needs, and direct strategic priorities. Facilitators and challenges revolved around the need for stakeholder buy-in, sufficient resources, senior leadership, and including patients in evaluations. CONCLUSIONS: A small but diverse set of HTA organizations evaluate their PPI activities using a range of strategies that reflect the range of rationales and approaches to PPI in HTA. It will be important for HTA organizations to draw on evaluation theories and methods.

Patients' perspectives can be integrated in health technology assessments: an exploratory analysis of CADTH Common Drug Review.

PLAIN LANGUAGE SUMMARY: In Canada, the CADTH Common Drug Review helps ensure that scarce health care resources are used to fund the most effective drugs. Clinicians, researchers, payers, and patients all have important, but potentially different, ideas on what should be considered, to determine a drug's value. Since 2010, CADTH has invited patient groups to contribute their perspectives to the Common Drug Review. We explored whether, and how, insights offered by patient groups are integrated into assessment reports and Recommendations by the CADTH Canadian Drug Expert Committee. After examining 30 completed drug assessments, we found that:Patient insights are used by CADTH reviewers to frame an assessment and are used by the expert committee to interpret the evidence.Drug trials do not always measure outcomes that patients consider important.Survival, symptom relief, the process of recovery, and maintaining health are all important aspects to consider when determining value during health technology assessments. ABSTRACT: Background Since 2010, Canadian patient groups have contributed to the CADTH Common Drug Review (CDR). CADTH conducts health technology assessments of new drugs to support publicly funded drug plans' reimbursement decisions. We explored whether, and how, patient insights were integrated into assessment reports and Recommendations by the CADTH Canadian Drug Expert Committee (CDEC). Methods We descriptively analyzed 30 consecutive assessments. One researcher identified a set of issues, insights, and desired treatment outcomes provided by patient groups for each included drug assessment. We tracked the presence of each identified patient insight in the relevant assessment protocol, in clinical trials as reported in the assessment, and in the CDEC Recommendations. Additionally, patient insights were categorized by topic and grouped into a three-tier framework to explore the observed juxtaposition between immediate treatment outcomes as seen in clinical trials and the insights from patients living with a chronic condition. Results In 30 drug assessments, 119 patient insights were identified. Of these insights, 89 were included in assessment protocols; 61 in reported clinical trial data; and 67 insights were reflected upon within the CDEC Recommendations. Patient insights within the first framework tier (health status achieved) were frequently included in all aspects of CDR assessments. Within the second tier (progress of recovery), although two-thirds of patient insights were included in protocols, only one-third was reflected in reported trial data or in CDEC Recommendations. Insights within the third tier, which address the long-term consequences of illness and treatment, were even less frequently addressed in all aspects of CDR assessments. Conclusions Patients' perspectives need not be "considered" in isolation. Patient insights are used by CADTH reviewers to frame an assessment and used by CDEC to interpret the evidence. As health technology assessments should address the indirect and unintended consequences of a technology, as well as its direct and intended effects, drug assessments should consider the progress of recovery and sustainability of health, in addition to survival and immediate health achieved.

Assessment of thiopurine S-methyltransferase activity in patients prescribed thiopurines: a systematic review.

BACKGROUND: The evidence for testing thiopurine S-methyltransferase (TPMT) enzymatic activity or genotype before starting therapy with thiopurine-based drugs is unclear. PURPOSE: To examine the sensitivity and specificity of TPMT genotyping for TPMT enzymatic activity, reducing harm from thiopurine by pretesting, and the association of thiopurine toxicity with TPMT status in adults and children with chronic inflammatory diseases. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Library, and Ovid HealthSTAR (from inception to December 2010) and BIOSIS and Genetics Abstracts (to May 2009). STUDY SELECTION: Two reviewers screened records and identified relevant studies in English. DATA EXTRACTION: Data on patient characteristics, outcomes, and risk for bias were extracted by one reviewer and independently identified by another. DATA SYNTHESIS: 54 observational studies and 1 randomized, controlled trial were included. Insufficient evidence addressed the effectiveness of pretesting. Genotyping sensitivity to identify patients with low and intermediate TPMT enzymatic activity ranged from 70.33% to 86.15% (lower-bound 95% CI, 54.52% to 70.88%; upper-bound CI, 78.50% to 96.33%). Sparse data precluded estimation of genotype sensitivity to identify patients with low to absent enzymatic activity. Genotyping specificity approached 100%. Compared with noncarriers, heterozygous and homozygous genotypes were both associated with leukopenia (odds ratios, 4.29 [CI, 2.67 to 6.89] and 20.84 [CI, 3.42 to 126.89], respectively). Compared with intermediate or normal activity, low TPMT enzymatic activity was significantly associated with myelotoxicity and leukopenia. LIMITATION: Available evidence was not rigorous and was underpowered to detect a difference in outcomes. CONCLUSION: Insufficient evidence addresses the effectiveness of TPMT pretesting in patients with chronic inflammatory diseases. Estimates of the sensitivity of genotyping are imprecise. Evidence confirms the known associations of leukopenia or myelotoxicity with reduced TPMT activity or variant genotype. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Naturopathic medicine and aboriginal health: an exploratory study at Anishnawbe Health Toronto.

OBJECTIVE: To explore the experiences and perceptions of providing and receiving naturopathic care within the Aboriginal community served by community health centre Anishnawbe Health Toronto. METHODS: This is an exploratory study using a descriptive qualitative approach to enable better understanding of the care provided to Aboriginal patients by naturopathic interns and clinician supervisors at Anishnawbe Health Toronto (AHT). We conducted semi-structured interviews with 3 naturopathic supervisors, 7 naturopathic interns, and 7 Aboriginal patients to gain an in-depth understanding of participants' experiences and perceptions of naturopathic medicine at AHT. We also conducted 3 confirmatory interviews with Naturopathic Doctors practicing in other Aboriginal communities. RESULTS: Naturopathic medicine is perceived to fit with health care philosophies in Aboriginal communities, as it emphasizes spiritual, mental and emotional aspects of health. Specifically, strengths of naturopathic medicine within the Aboriginal community relate to the philosophical suitability of naturopathic medicine, the ability to meet a wide range of health needs, the lack of power imbalance in the patient-practitioner relationship, and the cultural sensitivity of the practitioners. While AHT is highly regarded by patients and practitioners, certain limitations at the local setting regarding privacy and inter-professional communication were evident. Further, to facilitate trust, naturopathic interns require enhanced training in specific health issues that face the Aboriginal population to allow them to better engage with the culture and practices of the Aboriginal community. CONCLUSION: The naturopathic clinic at AHT contributes to positive patient outcomes and satisfaction and helps address unmet health needs in this population. Naturopathic medicine may be well suited to address Aboriginal health care needs through its holistic and respectful approach to care and a foundation of traditional knowledge and research evidence for treatment of a person's mind, body and spirit.

Complementary and alternative therapies for back pain II.

BACKGROUND: Back and neck pain are important health problems with serious societal and economic implications. Conventional treatments have been shown to have limited benefit in improving patient outcomes. Complementary and Alternative Medicine (CAM) therapies offer additional options in the management of low back and neck pain. Many trials evaluating CAM therapies have poor quality and inconsistent results. OBJECTIVES: To systematically review the efficacy, effectiveness, cost-effectiveness, and harms of acupuncture, spinal manipulation, mobilization, and massage techniques in management of back, neck, and/or thoracic pain. DATA SOURCES: MEDLINE, Cochrane Central, Cochrane Database of Systematic Reviews, CINAHL, and EMBASE were searched up to 2010; unpublished literature and reference lists of relevant articles were also searched. study selection: All records were screened by two independent reviewers. Primary reports of comparative efficacy, effectiveness, harms, and/or economic evaluations from randomized controlled trials (RCTs) of the CAM therapies in adults (age ≥ 18 years) with back, neck, or thoracic pain were eligible. Non-randomized controlled trials and observational studies (case-control, cohort, cross-sectional) comparing harms were also included. Reviews, case reports, editorials, commentaries or letters were excluded. DATA EXTRACTION: Two independent reviewers using a predefined form extracted data on study, participants, treatments, and outcome characteristics. RESULTS: 265 RCTs and 5 non-RCTs were included. Acupuncture for chronic nonspecific low back pain was associated with significantly lower pain intensity than placebo but only immediately post-treatment (VAS: -0.59, 95 percent CI: -0.93, -0.25). However, acupuncture was not different from placebo in post-treatment disability, pain medication intake, or global improvement in chronic nonspecific low back pain. Acupuncture did not differ from sham-acupuncture in reducing chronic non-specific neck pain immediately after treatment (VAS: 0.24, 95 percent CI: -1.20, 0.73). Acupuncture was superior to no treatment in improving pain intensity (VAS: -1.19, 95 percent CI: 95 percent CI: -2.17, -0.21), disability (PDI), functioning (HFAQ), well-being (SF-36), and range of mobility (extension, flexion), immediately after the treatment. In general, trials that applied sham-acupuncture tended to produce negative results (i.e., statistically non-significant) compared to trials that applied other types of placebo (e.g., TENS, medication, laser). Results regarding comparisons with other active treatments (pain medication, mobilization, laser therapy) were less consistent Acupuncture was more cost-effective compared to usual care or no treatment for patients with chronic back pain. For both low back and neck pain, manipulation was significantly better than placebo or no treatment in reducing pain immediately or short-term after the end of treatment. Manipulation was also better than acupuncture in improving pain and function in chronic nonspecific low back pain. Results from studies comparing manipulation to massage, medication, or physiotherapy were inconsistent, either in favor of manipulation or indicating no significant difference between the two treatments. Findings of studies regarding costs of manipulation relative to other therapies were inconsistent. Mobilization was superior to no treatment but not different from placebo in reducing low back pain or spinal flexibility after the treatment. Mobilization was better than physiotherapy in reducing low back pain (VAS: -0.50, 95 percent CI: -0.70, -0.30) and disability (Oswestry: -4.93, 95 percent CI: -5.91, -3.96). In subjects with acute or subacute neck pain, mobilization compared to placebo significantly reduced neck pain. Mobilization and placebo did not differ in subjects with chronic neck pain. Massage was superior to placebo or no treatment in reducing pain and disability only amongst subjects with acute/sub-acute low back pain. Massage was also significantly better than physical therapy in improving back pain (VAS: -2.11, 95 percent CI: -3.15, -1.07) or disability. For subjects with neck pain, massage was better than no treatment, placebo, or exercise in improving pain or disability, but not neck flexibility. Some evidence indicated higher costs for massage use compared to general practitioner care for low back pain. Reporting of harms in RCTs was poor and inconsistent. Subjects receiving CAM therapies reported soreness or bleeding on the site of application after acupuncture and worsening of pain after manipulation or massage. In two case-control studies cervical manipulation was shown to be significantly associated with vertebral artery dissection or vertebrobasilar vascular accident. CONCLUSIONS: Evidence was of poor to moderate grade and most of it pertained to chronic nonspecific pain, making it difficult to draw more definitive conclusions regarding benefits and harms of CAM therapies in subjects with acute/subacute, mixed, or unknown duration of pain. The benefit of CAM treatments was mostly evident immediately or shortly after the end of the treatment and then faded with time. Very few studies reported long-term outcomes. There was insufficient data to explore subgroup effects. The trial results were inconsistent due probably to methodological and clinical diversity, thereby limiting the extent of quantitative synthesis and complicating interpretation of trial results. Strong efforts are warranted to improve the conduct methodology and reporting quality of primary studies of CAM therapies. Future well powered head to head comparisons of CAM treatments and trials comparing CAM to widely used active treatments that report on all clinically relevant outcomes are needed to draw better conclusions.

Assessment of thiopurine methyltransferase activity in patients prescribed azathioprine or other thiopurine-based drugs.

OBJECTIVES: To examine whether pretreatment determination of thiopurine methyltransferase (TPMT) enzymatic activity (phenotyping) or TPMT genotype, to guide thiopurine therapy in chronic autoimmune disease patients, reduces treatment harms. Other objectives included assessing: preanalytic, analytic, and postanalytic requirements for TPMT testing; diagnostic accuracy of TPMT genotyping versus phenotyping; association of thiopurine toxicity with TPMT genotypic or phenotypic status; and costs of testing, care, and treating drug-associated complications. DATA SOURCES: MEDLINE®, EMBASE®, and Healthstar were searched from inception to May 2010; the Cochrane Library® to October 2009; and BIOSIS®, Genetics Abstracts, and EconLit™ to May 2009, for English language records. REVIEW METHODS: A reviewer screened records, and a second reviewer verified exclusions and subsequent selection of relevant studies. Studies in patients with leukemia and organ transplant were excluded. Additionally, laboratories that provide TPMT analytical services were surveyed to assess means of TPMT testing in practice. Where possible, risk of bias was assessed using standard criteria. Meta-analyses estimated diagnostic sensitivity, and specificity; and odds ratios of associations. RESULTS: 1790 titles or abstracts, and 538 full text records were screened. 114 observational studies and one RCT were included. Majority of studies were rated fair quality, except for diagnostic studies with 37 percent of studies rated poor. In general, there were few patients who were homozygous (or compound heterozygous) for TPMT variant alleles in the included studies limiting applicability. There is insufficient evidence examining effectiveness of pretesting in terms of reduction in clinical adverse events. Sufficient preanalytical data were available regarding preferred specimen collection, stability and storage conditions for TPMT testing. There was no clinically significant effect of age, gender, various coadministered drugs, or most morbidities (with the exception of renal failure and dialysis). TPMT phenotyping methods had coefficients of variation generally below 10 percent. TPMT genotyping reproducibility is generally between 95-100 percent. The sensitivity of genotyping to identify patients with low or intermediate TPMT enzymatic activity is imprecise, ranging from 70.70 to 82.10 percent (95 percent CI, lower bound range 37.90 to 54.00 percent; upper bound range 84.60 to 96.90 percent). Sensitivity of homozygous TPMT genotype to correctly identify patients with low to absent enzymatic activity was 87.10 percent (95 percent CI 44.30 to 98.30 percent). Genotyping specificity approached 100 percent. Leukopenia was significantly associated with low and intermediate enzymatic activity (low activity OR 80.00, 95 percent CI 11.5 to 559; and intermediate activity OR 2.96, 95 percent CI 1.18 to 7.42), and homozygous and heterozygous TPMT variant allele genotype (OR 18.60, 95 percent CI 4.12 to 83.60; and 4.62, 95 percent CI 2.34 to 9.16, respectively). In general, TPMT phenotyping costs less than genotyping, although estimates across studies are quite heterogeneous. CONCLUSIONS: There is insufficient direct evidence regarding the effectiveness of pretesting of TPMT status in patients with chronic autoimmune diseases. Indirect evidence confirms strong association of leukopenia with lower levels of TPMT activity and carrier genotype already established in the literature.