Talking about treatment.
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Antihypertensive Agents↗
Biomedical subjects
B Djulbegovic
Publications and source records attributed to B Djulbegovic.
Reporting and dissemination of industry versus non-profit sponsored economic analyses of six novel drugs used in oncology.
PURPOSE: Our prior study found that pharmaceutical-sponsored and non-profit sponsored analyses differed in their published assessments of the economic value of six new oncology drugs. In this study, we expand on our earlier findings and evaluate the association between funding source and 1) characteristics of the published study report and 2) journal type for dissemination of the previously evaluated economic studies. METHODS: We reviewed the published cost-effectiveness literature for hematopoietic colony stimulating factors, 5-HT3 antagonist antiemetics. and taxanes. Two blinded investigators rated specific aspects of study reporting based on the US Public Health Service Panel on Cost-effectiveness in Health and Medicine criteria. Dissemination strategies were evaluated using impact factor scores from the Science Citation Index. RESULTS: The operational aspects of pharmaceutical-sponsored study reporting were better overall than those associated with non-profit sponsored studies. Specifically, pharmaceutical-sponsored studies were more likely to be reported based on data obtained from randomized clinical trials or detailed cost-models (90% vs. 70%), to include descriptions of the source of cost differences (90% vs. 79%), to state whether the study was carried out from a societal, governmental, or insurer perspective (70% vs. 42%), and to clearly indicate the time-period over which costs were evaluated (65% vs. 50%). Nonprofit sponsored studies were more likely than pharmaceutical sponsored studies to report the generalizability of the findings, including being more likely to include information about how the data could be extrapolated to other clinical settings (58% vs. 35%), to include statements on the statistical significance of the findings (38% vs. 20%), and to clearly outline the cost per unit and data sources for the cost analyses (67% vs. 45%). A similar percent of pharmaceutical and non-profit sponsored studies reported background and conclusions with about 80% providing literature comparisons of the results (about 80%) and two thirds to three fourths discussing the limitations of the finding (75% for pharmaceutical-sponsored and 67% for non-profit sponsored studies). Most studies were published in low impact factor peer-reviewed journals, and journal impact factor scores were similar between pharmaceutical and nonprofit sponsored studies. CONCLUSIONS: Upon reviewing the entire pharmacoeconomic literature for six new oncology drugs, we identified differences in study reporting, but not in types of journals where studies were published, between pharmaceutical-sponsored and non-profit sponsored studies. These results, particularly the observed differences in data generalizability, may account in part for our previous finding of lower likelihood of reporting unfavorable conclusions in pharmaceutical-sponsored studies.
Antineoplastic Agents↗
Evidentiary challenges to evidence-based medicine.
The evidence-based medicine (EBM) movement has exerted a strong influence on contemporary medicine. It has been used to define the hierarchy of knowledge in clinical medicine by classifying clinical findings according to the perceived relevance and validity of the respective methodologies of studies from which evidence was collected. In the spectrum of theories of knowledge, EBM predominantly relies on findings obtained from population-derived clinical research. This reliance on knowledge obtained from population studies sharply contrasts with a physiologic model of clinical knowledge advocated by basic science researchers and many clinicians. An apparent schism between proponents of physiologic and population models in the approach to the practice of medicine has been created. This dichotomy between practising physicians and EBM physicians in the approach to clinical knowledge should not be irreconcilable. We advocate a consilient approach to the interpretation of evidence and the integration of medical knowledge. This approach relies on 'linking of facts and fact-based theory across various disciplines to create a common groundwork of explanation'.
Decision Making↗
Using the Internet to calculate clinical action thresholds.
Understanding the risks and benefits of available treatments represents an essential element of clinical practice. Previous work has demonstrated that knowledge of net benefits and net risks can relate to our decisions on whether or not to administer a particular treatment or order a diagnostic test. A wider application of this model has been difficult because data on net benefits and net risks are not directly reported. We used more frequently reported data on treatment efficacy (E) and risks (Rrx) to obtain an equation for the treatment threshold probability above which treatment should be given and below which it should be withheld. The diagnostic test should only be performed if the probability of a disease is between the testing threshold and the treatment threshold. We first described a theoretical background for these calculations. We then used a JavaScript programming language to write a computer program which physicians can use to calculate these threshold probabilities effortlessly through the Internet. In most clinical situations we do not have to achieve maximum diagnostic certainty in order to act. However, we should never treat or order a diagnostic test if the risk of the treatment is greater than its efficacy. The minimally required E/R ratio of a particular treatment is equal to the reciprocal value of the mortality/morbidity of untreated disease. Similarly, the lowest number of patients needed to be treated (NNT) for therapy to be worth administering is equal to the reciprocal of the treatment risk. We show how evidence-based summary measures of therapeutic effects, such as the treatment efficacy, harms, and NNT, can successfully be integrated within a decision analytic model. This in turn will facilitate wider use of the quantitative benefit-risk analysis. Accessing the Internet for direct and immediate approach to the formulas described here should make this task even easier in everyday clinical decision making.
Adult↗
The quality of medical evidence in hematology-oncology.
PURPOSE: The purpose of this study was to evaluate the quality of the medical evidence available to the clinician in the practice of hematology/oncology. METHODS: We selected 14 neoplastic hematologic disorders and identified 154 clinically important patient management decision/interventions, ranging from initial treatment decisions to those made for the treatment of recurrent or refractory disease. We also performed a search of the scientific literature for the years 1966 through 1996 to identify all randomized controlled trials in hematology/oncology. RESULTS: We identified 783 randomized controlled trials (level 1 evidence) pertaining to 37 (24%) of the decision/interventions. An additional 32 (21%) of the decision/interventions were supported by evidence from single arm prospective studies (level 2 evidence). However, only retrospective or anecdotal evidence (level 3 evidence) was available to support 55% of the identified decision/interventions. In a retrospective review of the decision/interventions made in the management of 255 consecutive patients, 78% of the initial decision/interventions in the management of newly diagnosed hematologic/oncologic disorders could have been based on level 1 evidence. However, more than half (52%) of all the decision/interventions made in the management of these 255 patients were supported only by level 2 or 3 evidence. CONCLUSIONS: We conclude that level 1 evidence to support the development of practice guidelines is available primarily for initial decision/interventions of newly diagnosed diseases. Level 1 evidence to develop guidelines for the management of relapsed or refractory malignant diseases is currently lacking.
Evidence-Based Medicine↗
Acceptable regret in medical decision making.
When faced with medical decisions involving uncertain outcomes, the principles of decision theory hold that we should select the option with the highest expected utility to maximize health over time. Whether a decision proves right or wrong can be learned only in retrospect, when it may become apparent that another course of action would have been preferable. This realization may bring a sense of loss, or regret. When anticipated regret is compelling, a decision maker may choose to violate expected utility theory to avoid regret. We formulate a concept of acceptable regret in medical decision making that explicitly introduces the patient's attitude toward loss of health due to a mistaken decision into decision making. In most cases, minimizing expected regret results in the same decision as maximizing expected utility. However, when acceptable regret is taken into consideration, the threshold probability below which we can comfortably withhold treatment is a function only of the net benefit of the treatment, and the threshold probability above which we can comfortably administer the treatment depends only on the magnitude of the risks associated with the therapy. By considering acceptable regret, we develop new conceptual relations that can help decide whether treatment should be withheld or administered, especially when the diagnosis is uncertain. This may be particularly beneficial in deciding what constitutes futile medical care.
Brain Ischemia↗
Reasoning by Identifying Goals of Treatment.
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Journal Article↗
High-Dose Chemotherapy in the Adjuvant Treatment of Breast Cancer: Benefit/Risk Analysis.
BACKGROUND: High-dose chemotherapy (HDRx) may improve the prognosis of patients with high-risk breast cancer but at the expense of increased toxicity. However, no randomized, controlled trials have been published that clearly demonstrate the superiority of HDRx over conventional adjuvant chemotherapy. METHODS: We developed a simple model to compare benefits and risks of HDRx with conventional adjuvant chemotherapy (SDRx). The model integrates data on efficacy and risks of two competing treatment strategies into a single decision rule. RESULTS AND CONCLUSIONS: Using data from phase II studies, we show that if a disease-free survival is considered to be the most important outcome, HDRx should be administered when the probability of breast cancer relapse at five years exceeds 54% to 71% for patients with 4 to 9 positive nodes and exceeds 29% to 40% for patients with >9 positive nodes. If the endpoint of interest is five-year overall survival, then the treatment should be administered when the probability of relapse exceeds 77% to 83% for patients with 4 to 9 nodes involved and 22% to 31% for those with >9 lymph nodes involved. While awaiting results of randomized, controlled trials to definitively establish the efficacy rate of HDRx, we also found that HDRx could be considered in the management of high-risk breast cancer if its efficacy rate is at least 54% to 60% superior to SDRx in reducing relapse risk in breast cancer patients with 4 to 9 nodes and at least 31% to 38% for >9 positive nodes. If survival data are used instead of disease-free survival outcomes, HDRx efficacy should be at least 47% to 48% superior to SDRx in reducing death risk in breast cancer patients with 4 to 9 nodes and at least 27% to 30% superior for >9 positive nodes to consider its use in the adjuvant setting.
Journal Article↗
Evaluating the quality of clinical guidelines. Linking decisions to medical evidence.
The validity and applicability of recommendations in clinical medicine are dependent on the design of studies upon which recommendations are based. Large prospective randomized controlled trials (RCT) generally provide the most reliable data to help guide our treatment decisions. However, analysis of decision-making in the field of hematologic malignancies indicates that only 24% of decisions can be based on randomized controlled trials. This lack of high-quality data to support many decisions in the treatment of malignant disorders underscores the need to evaluate the evidence that forms the backbone of guidelines themselves. As physicians are encouraged to conform to clinical guidelines, it is important that information be made available regarding the quality of data upon which these guidelines are based. We propose the development and use of a guideline quality score based on the quality of evidence supporting each decision in a guideline. By linking the quality of evidence with specific recommendations, physicians will be in a better position to understand the strengths and weaknesses of practice guidelines. This linkage will also help physicians to streamline their efforts to obtain a new line of evidence when an existing one is not satisfactory.
Decision Making↗
Safety and efficacy of purified factor IX concentrate and antifibrinolytic agents for dental extractions in hemophilia B.
This study evaluated the safety and efficacy of combined treatment with epsilon-aminocaproic acid or tranexamic acid and monoclonal antibody purified factor IX (MAb factor IX) for prophylaxis against bleeding in eight hemophilia B patients undergoing nine dental extraction procedures. All patients achieved excellent hemostasis without clinical evidence of thrombosis. There were no significant changes in hemoglobin or hematocrit or in markers of hemostatic system activation (prothrombin fragment F1+2, fibrinopeptide A, and fragment B beta 15-42) after surgery. Thus, a highly purified factor IX concentrate and antifibrinolytic therapy can be effectively and safely combined in hemophilia B patients undergoing dental extractions.
Adult↗
Clinical problem-solving: still hazy after all these years.
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Acute Disease↗
Guidelines for management of hemophilia A and B.
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Clinical Protocols↗
Lack of prophylactic anticoagulant therapy is not associated with clinical thrombotic complications in patients with hemophilia who undergo orthopedic surgical procedures.
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Adolescent↗
Diagnostic entropy as a function of therapeutic benefit/risk ratio.
Current clinical practice is based upon 'out stubborn quest for diagnostic certainty' which in turn is considered as one of the major reasons for ever-increasing health costs. We linked a treatment-threshold concept with classic information theory to show that measurable clinical variables, such as benefit and risk of available treatments, can be used to calculate the acceptable levels of diagnostic uncertainties associated with a particular clinical situation. Our analysis shows that practising physicians should aim for diagnostic certainty only when the benefit of treatment is equal to its associated risk. In all other cases, decisions about treatment do not have to rely on maximum diagnostic certainty. Determination of acceptable levels of diagnostic uncertainty according to the concepts outlined here should lead to improvement of clinical practice and decrease healthcare costs.
Appendicitis↗
Concomitant treatment with factor IX concentrates and antifibrinolytics in hemophilia B.
Concomitant use of the monoclonal antibody-purified factor IX concentrate (Mononine, Armour Pharmaceutical Company, Collegeville, Pa.) and two antifibrinolytic agents, epsilon-aminocaproic acid (EACA; Amicar, Immunex, Seattle, Wash.) or tranexamic acid (AMCA; Cyklokapron, Kabi Pharmacia, Piscataway, N.J.) was examined for safety and efficacy in patients with hemophilia B. In a retrospective review of 19 patients treated with monoclonal antibody-purified factor IX and EACA on 35 occasions, bleeding was successfully controlled and no instances of clinical thrombotic complications were reported; one instance of urticaria resolved without additional treatment. The use of EACA or AMCA in combination with monoclonal antibody-purified factor IX was also examined prospectively in a study of 9 patients. Bleeding was effectively controlled and no thrombotic events were detected clinically with either antifibrinolytic agent. No significant changes in hematocrit or hemoglobin were detected, and there was no evidence of thrombosis as evaluated clinically and by sensitive molecular markers. It was concluded from both the retrospective and prospective data that monoclonal antibody-purified factor IX concentrate in combination with an antifibrinolytic agent does not activate the coagulation cascade and is a safe and effective treatment for prevention and control of oral bleeding in hemophilia B patients.
Aminocaproates↗
HLA-DR53 protects against thrombotic thrombocytopenic purpura/adult hemolytic uremic syndrome.
Class I and Class II HLA antigens were tested in patients treated for thrombotic thrombocytopenic purpura or hemolytic uremic syndrome (TTP/HUS) to determine whether there is a disease association. Based on the results of a pilot trial, retrospective HLA-typing of 18 patients with a diagnosis of TTP/HUS and prospective typing of 12 newly diagnosed patients with TTP/HUS were performed. Twenty-one patients were non-Hispanic Caucasians, 7 were African-Americans, and 2 were Hispanic-Caucasians. Of 30 patients tested, 28 were positive for DR52 (chi-squared = 5.14, P < 0.05), and only two were positive for DR53 compared to 57% of controls (chi-squared = 18.5, P < 0.0005). Diverse DR52 subtypes (DRB3*0101, DRB3*02, and DRB3*0301) were found by oligonucleotide testing in 15 patients, suggesting the association was not with DR52 but with absence of the DR53 antigen. The 2 patients with DR53 were not homozygous. This study suggests that the supertypic antigen, DR53, may govern susceptibility to TTP/HUS, since the relative risk of this disease among DR53 positives is reduced at 0.09 (95% confidence interval, 0.01-0.28). This finding indicates a possible immunogenetic component in the pathogenesis of TTP.
Adult↗
High-dose chlorambucil and dexamethasone for relapsed non-Hodgkin's lymphomas.
Twenty patients with relapsed or refractory non-Hodgkin's lymphoma were treated with high-dose chlorambucil (14 mg/m2 every 6 hours for 6 doses) and dexamethasone (40 mg/day for 5 days). There was a 45% response rate with 17% complete responses. The median duration of complete response was 7 months. The regimen was well tolerated and had minimal toxicity.
Adult↗
Residual mediastinal mass after treatment of Hodgkin's disease: a decision analysis.
A residual mediastinal mass after completion of initial treatment for Hodgkin's disease is a frequent clinical problem. Investigators have suggested three possible approaches to this important problem: 1) observation, 2) additional diagnostic tests with subsequent action based upon test results, or 3) immediate treatment for high-risk patients. The method of decision analysis was applied to determine the optimal management for residual mediastinal abnormalities following treatment of Hodgkin's disease with combined modalities of MOPP chemotherapy and radiation therapy. The three parameters of the importance for making the best decision were: 1) the probability that the mass is truly active disease, 2) the salvage success rate using MOPP or ABVD treatment and 3) the specificity of the gallium scan. The analysis favored the gallium imaging strategy as an initial management choice when the probability was greater than 3% that the residual mass represented active disease and the specificity of gallium imaging was greater than 56%. This strategy proved to be the most cost effective, as well. Additional chemotherapy was favored only when there was a greater than 99% probability that the mass represented active disease. A nomogram has been constructed combining all three parameters of importance for graphically determining the best decision.
Antineoplastic Combined Chemotherapy Protocols↗