The Cochrane Handbook for Systematic Reviews of Interventions is the official document that describes in detail the process of preparing and maintaining Cochrane systematic reviews on the effects of healthcare interventions.

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Cochrane Handbook for Systematic Reviews of Interventions

Chronic obstructive pulmonary disease (COPD) remains a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States, and is projected to rank fifth in 2020 in burden of disease worldwide, according to a study published by the World Bank/World Health Organization. Yet, COPD remains relatively unknown or ignored by the public as well as public health and government officials. In 1998, in an effort to bring more attention to COPD, its management, and its prevention, a committed group of scientists encouraged the U.S. National Heart, Lung, and Blood Institute and the World Health Organization to form the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Among the important objectives of GOLD are to increase awareness of COPD and to help the millions of people who suffer from this disease and die prematurely of it or its complications. The first step in the GOLD program was to prepare a consensus report, Global Strategy for the Diagnosis, Management, and Prevention of COPD, published in 2001. The present, newly revised document follows the same format as the original consensus report, but has been updated to reflect the many publications on COPD that have appeared. GOLD national leaders, a network of international experts, have initiated investigations of the causes and prevalence of COPD in their countries, and developed innovative approaches for the dissemination and implementation of COPD management guidelines. We appreciate the enormous amount of work the GOLD national leaders have done on behalf of their patients with COPD. Despite the achievements in the 5 years since the GOLD report was originally published, considerable additional work is ahead of us if we are to control this major public health problem. The GOLD initiative will continue to bring COPD to the attention of governments, public health officials, health care workers, and the general public, but a concerted effort by all involved in health care will be necessary.

https://www.who.int/respiratory/copd/GOLD_WR_06.pdf

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.

Much biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study's generalisability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September 2004, with methodologists, researchers, and journal editors to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE Statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles. 18 items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies. A detailed Explanation and Elaboration document is published separately and is freely available on the Web sites of PLoS Medicine, Annals of Internal Medicine, and Epidemiology. We hope that the STROBE Statement will contribute to improving the quality of reporting of observational studies.

/pdf/the-strengthening-the-reporting-of-observational-studies-in-1a60tcw2sx.pdf

The Strengthening the Reporting of Observational Studies in Epidemiology [STROBE] statement: guidelines for reporting observational studies

Much biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study’s generalizability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, case-control and cross-sectional studies. We convened a two-day workshop, in September 2004, with methodologists, researchers and journal editors to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE Statement) that relate to the title, abstract, introduction, methods, results and discussion sections of articles. Eighteen items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies. A detailed Explanation and Elaboration document is published separately and is freely available on the web sites of PLoS Medicine, Annals of Internal Medicine and Epidemiology. We hope that the STROBE Statement will contribute to improving the quality of reporting of observational studies.

/pdf/the-strengthening-the-reporting-of-observational-studies-in-5fvhasotyl.pdf

The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies

XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

Genome-Wide Association Studies of Schizophrenia and Bipolar Disorder in a Diverse Cohort of US Veterans

The aim of the present study was to evaluate, among older persons, the association between respiratory impairment and hospitalisation for chronic obstructive pulmonary disease (COPD), based on spirometric Z-scores, i.e. the LMS (lambda, mu, sigma) method, and a competing risk approach. Using data on 3,563 white participants aged 65-80 yrs (from the Cardiovascular Health Study) we evaluated the association of LMS-defined respiratory impairment with the incident of COPD hospitalisation and the competing outcome of death without COPD hospitalisation, over a 5-yr period. Respiratory impairment included airflow limitation (mild, moderate or severe) and restrictive pattern. Over a 5-yr period, 276 (7.7%) participants had a COPD hospitalisation incident, whereas 296 (8.3%) died without COPD hospitalisation. The risk of COPD hospitalisation was elevated more than two-fold in LMS-defined mild and moderate airflow limitation and restrictive pattern (adjusted HR (95% CI): 2.25 (1.25-4.05), 2.54 (1.53- 4.22) and 2.65 (1.82-3.86), respectively), and more than eight-fold in LMS-defined severe airflow limitation (adjusted HR (95% CI) 8.33 (6.24-11.12)). Conversely, only LMS-defined restrictive-pattern was associated with the competing outcome of death without COPD hospitalisation (adjusted HR (95% CI) 1.68 (1.22-2.32)). In older white persons, LMS-defined respiratory impairment is strongly associated with an increased risk of COPD hospitalisation. These results support the LMS method as a basis for defining respiratory impairment in older persons.

https://erj.ersjournals.com/content/erj/40/1/37.full.pdf

Respiratory impairment and COPD hospitalisation in older persons: a competing risk analysis.

OBJECTIVE: Some people believe that certain issues should be protected from all trade-offs. These issues are referred to as "protected values." We investigated whether some patients with rheumatoid arthritis (RA) treat the risk of adverse effects (AE) as "protected values," i.e., as unacceptable regardless of how small the risk. METHODS: Patients with RA rated willingness to risk 17 different AE on a visual analog scale, where 0 = not willing under any circumstances and 100 = definitely willing. Participants then rated willingness to take medication as the risk of each AE was progressively decreased by 2 levels from its actual risk, using a 5 level scale ranging from 10 in 100 to 1 in 100,000. RESULTS: Between 32% and 39% of participants were not more willing to accept a risk of AE causing reversible cosmetic changes (e.g., acne), between 35% and 47% were not more willing to accept a risk of AE causing reversible discomfort (e.g., rash), and between 41% and 45% were not more willing to accept a risk of AE causing potential irreversible damage (e.g., pneumonitis) as the probability of each of these AE was substantially decreased. Unwillingness to accept risk of toxicity was especially evident for cancer, where 66% of patients refused to accept a risk of cancer occurring in 1 in 100,000 persons. CONCLUSION: Among patients particularly concerned with the risk of drug toxicity, many remain unwilling to accept the risk of AE even when their probability is decreased to levels far below their actual risk. These results suggest that patients may treat particularly worrisome AE as protected values, which may lead to poor decision-making in clinical practice.

https://www.jrheum.org/content/jrheum/30/3/443.full.pdf

Risk communication in rheumatoid arthritis.

M than 5 years after the passage of the 21st Century Cures Act of 2016, the terms “realworld data” (RWD) and “real-world evidence” (RWE) are being used inconsistently and sometimes interchangeably. This imprecision has complicated efforts to assess the impact of such data and evidence and hindered attempts to track their use. The Food and Drug Administration (FDA), in its Framework for FDA’s Real-World Evidence Program,1 defined RWD as “data relating to patient health status and/or the delivery of health care routinely collected from a variety of sources” and defined RWE as “clinical evidence about the usage and potential benefits or risks of a medical product derived from analysis of RWD,” regardless of the type of study design. But there are two widespread misconceptions about these terms. The first is the notion that RWD and RWE were brand-new concepts in 2016. In reality, sources of data and types of study designs haven’t fundamentally changed, but electronic access to more detailed clinical data is evolving, and such information’s reliability and relevance to research are improving. The availability of more robust data on clinical factors that affect health outcomes also provides opportunities for exploring various statistical methods in lieu of randomization. Including “RWD” or “RWE” in the description of a study, however, doesn’t tell us exactly where the data came from or what kind of study architecture is involved. Providing more specifics about data sources and study design can reduce confusion over RWD and RWE.2 The second misconception is that a simple dichotomy between randomized, controlled trials (RCTs) and observational studies delineates the entire landscape of study design.3 Although randomization of treatment assignment is a key strength of RCTs, not all clinical trials are randomized; rather, their defining feature is assignment of treatment according to an investigational protocol. For example, in single-group trials, investigators assign participants to receive an intervention without randomization — and face challenges similar to those in observational studies in determining whether differences in clinical outcomes between the protocol-driven group and a comparator (“control”) group represent actual treatment effects. Correcting these misconceptions requires recognition that the degree of reliance on RWD varies with the type of study design and that, by definition, RCTs that incorporate RWD generate RWE (see diagram). This conceptualization confirms that even when strict eligibility criteria may limit the generalizability of trial results, trial participants exist, and their outcomes occur, in the “real world” — despite perceptions that generation of RWE occurs only outside clinical trials. Also, although the terms “clinical trials” and “observational studies” have clear meanings when used properly, the terms “interventional studies” and “noninterventional studies” have advantages in describing whether the treatment of interest was administered according to a study protocol. These conceptual distinctions were less pertinent when causal inferences regarding therapeutic effectiveness relied mainly on interventional studies with primary data collected in traditional RCTs. Increasingly, however, RCTs incorporate RWD, and when randomization isn’t feasible for ethical or other reasons, externally controlled trials include a comparator group derived entirely from a source of secondary data (“external” to the treatment group). Conversely, noninterventional studies that analyze primary data collected from registries are being conducted more often. Notwithstanding confusion regarding these terms and concepts, we at the FDA continue to evaluate RWD and RWE as we consider regulatory decisions. Indeed, the agency published four related draft guidance documents in 2021.4 FDA guidance on data from electronic health records and medical claims databases includes recommendations on how to select relevant data sources and define and validate study variables; other guidance provides recommendations on designing or using an existing registry to support regulatory decision making. A guidance document on data standards advises sponsors to document a rationale for changes

Real-World Evidence - Where Are We Now?

Objective Impairments in cognition and everyday functioning are common in schizophrenia and bipolar disorder (BPD). In this article, we present factor analyses of cognitive and functional capacity (FC) measures based on 2 studies of schizophrenia (SCZ) and bipolar I disorder (BPI) using similar methods. The overall goal of these analyses was to determine whether performance-based assessments should be examined individually, or aggregated on the basis of the correlational structure of the tests, as well as to evaluate the similarity of factor structures of SCZ and BPI. Method Veterans Affairs Cooperative Studies Program Study #572 (Harvey et al., 2014) evaluated cognitive and FC measures among 5,414 BPI and 3,942 SCZ patients. A 2nd study evaluated similar neuropsychological (NP) and FC measures among 368 BPI and 436 SCZ patients. Principal components analysis, as well as exploratory and CFAs, were used to examine the data. Results Analyses in both datasets suggested that NP and FC measures were explained by a single underlying factor in BPI and SCZ patients, both when analyzed separately or as in a combined sample. The factor structure in both studies was similar, with or without inclusion of FC measures; homogeneous loadings were observed for that single factor across cognitive and FC domains across the samples. Conclusion The empirically derived factor model suggests that NP performance and FC are best explained as a single latent trait applicable to people with SCZ and BPD. This single measure may enhance the robustness of the analyses relating genomic data to performance-based phenotypes.

John Concato

Papers

Genome-Wide Association Studies of Schizophrenia and Bipolar Disorder in a Diverse Cohort of US Veterans

Respiratory impairment and COPD hospitalisation in older persons: a competing risk analysis.

Risk communication in rheumatoid arthritis.

Real-World Evidence - Where Are We Now?

Factor structure of cognition and functional capacity in two studies of schizophrenia and bipolar disorder: Implications for genomic studies.