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BACKGROUND: Based on the Khorana score, guidelines recommend anticoagulation for primary prophylaxis (PP) in outpatients with cancer with an intermediate-to-high risk of venous thromboembolism (VTE). ONKOTEV score has been prospectively externally validated as novel risk assessment model (RAM) with good discriminatory performances but no direct comparisons with Khorana Score are available. METHODS: Using the ONKOTEV validation dataset (n = 425), we applied generalized decision curve analysis (gDCA) which integrates the principles of evidence-based medicine with treatment effects, model accuracy and patient preferences (weighted as the relative value [RV] of avoiding VTE versus major bleeding [MB]). The aim is to select the most optimal treatment strategy among multiple options: "no treatment", "treat all patients with DOAC/LMVH", or "use ONKOTEV/KHORANA scores to guide PP with DOAC/LMWH". RESULTS: Results showed that ONKOTEV-guided PP (using DOAC or LMWH) remained the most optimal strategy for wide range assumption of treatment efficacy and patient's preference. For those patients, who value avoiding VTE more than MB, then offering DOAC to all patients represents the best strategy. When MBs are feared more than the morbidity of VTE, ONKOTEV-guided PP (DOAC) represents the best management strategy. In all cases, ONKOTEV outperformed Khorana for individualized VTE prevention. CONCLUSIONS: When the two predictive models are integrated within a decision analysis framework, ONKOTEV appears superior to Khorana Score in guiding individualized prevention of cancer-related VTE in outpatients with cancer. The findings herein reported provide cutting edge insights in cancer care and support the spread of ONKOTEV score in the ambulatory cancer setting.
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Consensus statements can be very influential in medicine and public health. Some of these statements use systematic evidence synthesis but others fail on this front. Many consensus statements use panels of experts to deduce perceived consensus through Delphi processes. We argue that stacking of panel members toward one particular position or narrative is a major threat, especially in absence of systematic evidence review. Stacking may involve financial conflicts of interest, but nonfinancial conflicts of strong advocacy can also cause major bias. Given their emerging importance, we describe here how such consensus statements may be misleading, by analyzing in depth a recent high-impact Delphi consensus statement on COVID-19 recommendations as a case example. We demonstrate that many of the selected panel members and at least 35% of the core panel members had advocated toward COVID-19 elimination (Zero-COVID) during the pandemic and were leading members of aggressive advocacy groups. These advocacy conflicts were not declared in the Delphi consensus publication, with rare exceptions. Therefore, we propose that consensus statements should always require rigorous evidence synthesis and maximal transparency on potential biases toward advocacy or lobbyist groups to be valid. While advocacy can have many important functions, its biased impact on consensus panels should be carefully avoided.
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OBJECTIVES: To assess to what extent the overall quality of evidence indicates changes to observe intervention effect estimates when new data become available. METHODS: We conducted a meta-epidemiological study. We obtained evidence from meta-analyses of randomized trials of Cochrane reviews addressing the same health-care question that was updated with inclusion of additional data between January 2016 and May 2021. We extracted the reported effect estimates with 95% confidence intervals (CIs) from meta-analyses and corresponding GRADE (Grading of Recommendations Assessment, Development, and Evaluation) assessments of any intervention comparison for the primary outcome in the first and the last updated review version. We considered the reported overall quality (certainty) of evidence (CoE) and specific evidence limitations (no, serious or very serious for risk of bias, imprecision, inconsistency, and/or indirectness). We assessed the change in pooled effect estimates between the original and updated evidence using the ratio of odds ratio (ROR), absolute ratio of odds ratio (aROR), ratio of standard errors (RoSE), direction of effects, and level of statistical significance. RESULTS: High CoE without limitations characterized 19.3% (n = 29) out of 150 included original Cochrane reviews. The update with additional data did not systematically change the effect estimates (mean ROR 1.00; 95% CI 0.99-1.02), which deviated 1.06-fold from the older estimates (median aROR; interquartile range [IQR]: 1.01-1.15), gained precision (median RoSE 0.87; IQR 0.76-1.00), and maintained the same direction with the same level of statistical significance in 93% (27 of 29) of cases. Lower CoE with limitations characterized 121 original reviews and graded as moderate CoE in 30.0% (45 of 150), low CoE in 32.0% (48 of 150), and very low CoE in 18.7% (28 of 150) reviews. Their update had larger absolute deviations (median aROR 1.12 to 1.33) and larger gains in precision (median RoSE 0.78-0.86) without clear and consistent differences between these categories of CoE. Changes in effect direction or statistical significance were also more common in the lower quality evidence, again with a similar extent across categories (without change in 75.6%, 64.6%, and 75.0% for moderate, low, very low CoE). As limitations increased, effect estimates deviated more (aROR 1.05 with zero, 1.11 with one, 1.25 with two, 1.24 with three limitations) and changes in direction or significance became more frequent (93.2% stable with no limitations, 74.5% with one, 68.2% with two, and 61.5% with three limitations). CONCLUSION: High-quality evidence without methodological deficiencies is trustworthy and stable, providing reliable intervention effect estimates when updated with new data. Evidence of moderate and lower quality may be equally prone to being unstable and cannot indicate if available effect estimates are true, exaggerated, or underestimated.
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Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto/normas , Medicina Basada en la Evidencia/normas , Medicina Basada en la Evidencia/métodos , Metaanálisis como Asunto , Revisiones Sistemáticas como Asunto/métodosRESUMEN
ABSTRACT: Current hospital venous thromboembolism (VTE) prophylaxis for medical patients is characterized by both underuse and overuse. The American Society of Hematology (ASH) has endorsed the use of risk assessment models (RAMs) as an approach to individualize VTE prophylaxis by balancing overuse (excessive risk of bleeding) and underuse (risk of avoidable VTE). ASH has endorsed IMPROVE (International Medical Prevention Registry on Venous Thromboembolism) risk assessment models, the only RAMs to assess short-term bleeding and VTE risk in acutely ill medical inpatients. ASH, however, notes that no RAMs have been thoroughly analyzed for their effect on patient outcomes. We aimed to validate the IMPROVE models and adapt them into a simple, fast-and-frugal (FFT) decision tree to evaluate the impact of VTE prevention on health outcomes and costs. We used 3 methods: the "best evidence" from ASH guidelines, a "learning health system paradigm" combining guideline and real-world data from the Medical University of South Carolina (MUSC), and a "real-world data" approach based solely on MUSC data retrospectively extracted from electronic records. We found that the most effective VTE prevention strategy used the FFT decision tree based on an IMPROVE VTE score of ≥2 or ≥4 and a bleeding score of <7. This method could prevent 45% of unnecessary treatments, saving â¼$5 million annually for patients such as the MUSC cohort. We recommend integrating IMPROVE models into hospital electronic medical records as a point-of-care tool, thereby enhancing VTE prevention in hospitalized medical patients.
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Árboles de Decisión , Hemorragia , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/etiología , Medición de Riesgo , Anticoagulantes/uso terapéutico , Factores de RiesgoRESUMEN
ABSTRACT: The American Society of Hematology (ASH) develops a variety of resources that provide guidance to clinicians on the diagnosis and management of blood diseases. These resources include clinical practice guidelines (CPGs) and other forms of clinical advice. Although both ASH CPGs and other forms of clinical advice provide recommendations, they differ with respect to the methods underpinning their development, the principal type of recommendations they offer, their transparency and concordance with published evidence, and the time and resources required for their development. It is crucial that end users be aware of the differences between CPGs and other forms of clinical advice and that producers and publishers of these resources use clear and unambiguous terminology to facilitate their distinction. The objective of this article is to highlight the similarities and differences between ASH CPGs and other forms of ASH clinical advice and discuss the implications of these differences for end users.
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Hematología , Guías de Práctica Clínica como Asunto , Humanos , Hematología/normas , Sociedades Médicas , Estados UnidosRESUMEN
ABSTRACT: Decision analysis can play an essential role in informing practice guidelines. The American Society of Hematology (ASH) thrombophilia guidelines have made a significant step forward in demonstrating how decision modeling integrated within Grading of Recommendations Assessment, Developing, and Evaluation (GRADE) methodology can advance the field of guideline development. Although the ASH model was transparent and understandable, it does, however, suffer from certain limitations that may have generated potentially wrong recommendations. That is, the panel considered 2 models separately: after 3 to 6 months of index venous thromboembolism (VTE), the panel compared thrombophilia testing (A) vs discontinuing anticoagulants (B) and testing (A) vs recommending indefinite anticoagulation to all patients (C), instead of considering all relevant options simultaneously (A vs B vs C). Our study aimed to avoid what we refer to as the omitted choice bias by integrating 2 ASH models into a single unifying threshold decision model. We analyzed 6 ASH panel's recommendations related to the testing for thrombophilia in settings of "provoked" vs "unprovoked" VTE and low vs high bleeding risk (total 12 recommendations). Our model disagreed with the ASH guideline panels' recommendations in 4 of the 12 recommendations we considered. Considering all 3 options simultaneously, our model provided results that would have produced sounder recommendations for patient care. By revisiting the ASH guidelines methodology, we have not only improved the recommendations for thrombophilia but also provided a method that can be easily applied to other clinical problems and promises to improve the current guidelines' methodology.
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Guías de Práctica Clínica como Asunto , Trombofilia , Humanos , Trombofilia/diagnóstico , Trombofilia/etiología , Trombofilia/tratamiento farmacológico , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/etiología , Técnicas de Apoyo para la Decisión , Anticoagulantes/uso terapéuticoRESUMEN
OBJECTIVES: Evidence-based research (EBR) is the systematic and transparent use of prior research to inform a new study so that it answers questions that matter in a valid, efficient, and accessible manner. This study surveyed experts about existing (e.g., citation analysis) and new methods for monitoring EBR and collected ideas about implementing these methods. STUDY DESIGN AND SETTING: We conducted a cross-sectional study via an online survey between November 2022 and March 2023. Participants were experts from the fields of evidence synthesis and research methodology in health research. Open-ended questions were coded by recurring themes; descriptive statistics were used for quantitative questions. RESULTS: Twenty-eight expert participants suggested that citation analysis should be supplemented with content evaluation (not just what is cited but also in which context), content expert involvement, and assessment of the quality of cited systematic reviews. They also suggested that citation analysis could be facilitated with automation tools. They emphasized that EBR monitoring should be conducted by ethics committees and funding bodies before the research starts. Challenges identified for EBR implementation monitoring were resource constraints and clarity on responsibility for EBR monitoring. CONCLUSION: Ideas proposed in this study for monitoring the implementation of EBR can be used to refine methods and define responsibility but should be further explored in terms of feasibility and acceptability. Different methods may be needed to determine if the use of EBR is improving over time.
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Proyectos de Investigación , Humanos , Estudios TransversalesRESUMEN
BACKGROUND: To realize the potential of precision medicine, predictive models should be integrated within the framework of decision analysis, such as the decision curve analysis (DCA). To date, its application has required individual patient data (IPD) that are often unavailable. Performing DCA using aggregate data without requiring IPD may advance the goals of precision medicine. METHODS: We present a statistical framework demonstrating that DCA can be conducted by using only the mean and standard deviation (SD) from the raw probabilities of the predictive model. We tested our theoretical framework by performing extensive simulations and comparing the aggregate-based DCA with IPD DCA. The latter was conducted using IPD from four predictive models that employed logistic regression, Cox or competing risk time-to-event modeling including (a) statins for primary prevention of cardiovascular disease (n = 4859), (b) hospice referral for terminally ill patients (n = 9104), (c) use of thromboprophylaxis for preventing venous thromboembolism in patients with cancer (n = 425) and (d) prevention of sinusoidal obstruction syndrome after hematopoietic cell transplantation (SCT) (n = 80). RESULTS: Simulations assuming perfect calibration showed that regardless of which probability distributions informed the predictive models, the differences in DCA were negligible. Similarly, for the adequately powered models, the results of DCA based on the summary data were similar to IPD-derived DCA. The inherent instability of the predictive models, based on the smaller sample sizes, resulted in a somewhat larger discrepancy between aggregate and IPD-based DCA. CONCLUSIONS: DCA informed by adequately powered and well-calibrated models using only summary statistical estimates (mean and SD) approximates well models using IPD. Use of aggregate data will facilitate broader integration of predictive with decision modeling toward the goals of individualized decision-making.
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Anticoagulantes , Tromboembolia Venosa , Humanos , Modelos LogísticosRESUMEN
OBJECTIVES: To synthesize empirical studies that investigate the cognitive and social processes involved in the deliberation process of guideline development meetings and determine the distribution of deliberated topics. STUDY DESIGN AND SETTING: We conducted a mixed-method systematic review using a convergent segregated approach. We searched for empirical studies that investigate the intragroup dynamics of guideline development meetings indexed in bibliographic databases. RESULTS: Of the 5,899 citations screened, 12 studies from six countries proved eligible. Chairs, cochairs, and methodologists contributed to at least one-third of the discussion time in guideline development meetings; patient partners contributed the least. In interdisciplinary groups, male gender and occupation as a physician were positively associated with the amount of contribution. Compared to groups that used the Grading of Recommendations Assessment, Development and Evaluation approach, for groups that did not, when faced with insufficient or low-quality evidence, relied more on their clinical experience. The presence of a cognitive "yes" bias was apparent in meetings: panelists tended to acquiesce with positive statements that required less cognitive effort than negative statements. CONCLUSION: The social dynamics of the discussions were linked to each panelist's activity role, professional background, and gender, all of which influenced the level of contributions they made in guideline development meetings.
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Dinámica de Grupo , Humanos , Investigación Empírica , Guías de Práctica Clínica como AsuntoRESUMEN
BACKGROUND: Current methods for developing clinical practice guidelines have several limitations: they are characterised by the "black box" operation-a process with defined inputs and outputs but an incomplete understanding of its internal workings; they have "the integration problem"-a lack of framework for explicitly integrating factors such as patient preferences and trade-offs between benefits and harms; they generate one recommendation at a time that typically are not connected in a coherent analytical framework; and they apply to "average" patients, while clinicians and their patients seek advice tailored to individual circumstances. METHODS: We propose augmenting the current guideline development method by converting evidence-based pathways into fast-and-frugal decision trees (FFTs) and integrating them with generalised decision curve analysis to formulate clear, individualised management recommendations. RESULTS: We illustrate the process by developing recommendations for the management of heparin-induced thrombocytopenia (HIT). We converted evidence-based pathways for HIT, developed by the American Society of Hematology, into an FFT. Here, we consider only thrombotic complications and major bleeding. We leveraged the predictive potential of FFTs to compare the effects of argatroban, bivalirudin, fondaparinux, and direct oral anticoagulants (DOACs) using generalised decision curve analysis. We found that DOACs were superior to other treatments if the FFT-predicted probability of HIT exceeded 3%. CONCLUSIONS: The proposed analytical framework connects guidelines, pathways, FFTs, and decision analysis, offering risk-tailored personalised recommendations and addressing current guideline development critiques.
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Trombocitopenia , Humanos , Trombocitopenia/inducido químicamente , Técnicas de Apoyo para la Decisión , Atención al PacienteRESUMEN
In this chapter, we illustrate how evidence about treatments' benefits and harms can be integrated to enable rational decision-making even under considerable clinical uncertainty.
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Toma de Decisiones Clínicas , Toma de Decisiones , Humanos , Incertidumbre , Técnicas y Procedimientos DiagnósticosRESUMEN
Today, every country struggles to provide adequate health care to its citizens. Globally, an average of $8.3 trillion or 10% of gross domestic product (GDP) is annually spent on health services. In 2019, the USA spent nearly 18% ($3.2 trillion) of its GDP on health care, projected to reach $6.2 trillion by 2028.
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Producto Interno Bruto , Humanos , PredicciónRESUMEN
In Chap. 2 , we illustrated the application of the expected utility theory (EUT) to rational decision-making when no further diagnostic testing is available. In this chapter, we apply regret theory to the decision problems discussed in Chap. 2 .
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Técnicas y Procedimientos Diagnósticos , Emociones , Humanos , Toma de DecisionesRESUMEN
When a decision-maker has the option of diagnostic testing, they face a typical dilemma: (1) do not administer treatment and do not test, (2) test and decide to administer treatment based on the test result, and (3) administer treatment without testing. In this chapter, we will discuss the theory behind threshold modeling when diagnostic testing is available; we will illustrate the approach by presenting a case vignette.
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Toma de Decisiones , Técnicas y Procedimientos Diagnósticos , HumanosRESUMEN
Clinical management is rarely based on the collection of one data item. Instead, it is typically characterized by the continuous collection and evaluation of clinical data (symptoms, signs, laboratory, imaging tests, etc.) to establish a platform for further management decisions.
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Vías Clínicas , Árboles , Humanos , Sistemas de Atención de PuntoRESUMEN
In this chapter, we extend the threshold model to evaluate the value of diagnostic tests or predictive models over a range of all possible thresholds by using decision curve analysis (DCA). DCA has been developed within the expected utility theory (EUT) and expected regret theory (ERT) framework.
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Técnicas de Apoyo para la Decisión , Técnicas y Procedimientos Diagnósticos , HumanosRESUMEN
In the previous chapters, we presented various derivations of the threshold model based on the same disease outcomes. We assumed that a decision-maker would calculate the threshold based on either mortality or morbidity outcomes. Basinga and van den Ende derived the threshold by combining both mortality and morbidity outcomes.
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In this chapter, we discuss the potential role that artificial intelligence (AI) may have in medical decision-making, the pros and cons, and the limitations and biases that might be introduced when using these novel techniques. As computing becomes more powerful and models continue to grow increasingly more complex, the potential of AI to improve decision-making is increasingly promising. Within many medical fields, however, at the time of this writing (September 2023), the promise of AI is yet to translate into everyday reality. Here, we summarize the role of AI in medical decision-making (diagnosis, prognosis, and treatment).