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PubMed2003

Cost-effectiveness of a transplantation strategy compared to melphalan and prednisone in younger patients with multiple myeloma.

High dose chemotherapy with autologous stem cell transplantation (ASCT) improves outcomes in patients 65 years of age or less with multiple myeloma. Survival and costs in a cohort of 16 patients who received melphalan and prednisone as part of a clinical trial were compared with those of 36 patients referred to our centre for consideration of ASCT. In the transplant group, survival and costs were extrapolated to match the period of observation in the melphalan and prednisone group. Patient-specific and average costs were calculated from the perspective of the Ontario Ministry of Health. Costs and survival were varied by 50% in the sensitivity analysis. Transplantation improved life expectancy by 19.3 months with a cost difference of 30,517 Canadian dollars. The incremental cost-effectiveness of transplantation compared with melphalan and prednisone was 25,710 Canadian dollars per life-year gained when additional pamidronate and follow-up costs were considered. Discounting costs and survival at 3 and 5% did not result in important differences. The sensitivity analysis resulted in best and worse case scenarios for transplantation compared with melphalan and prednisone of 13,049 dollars and 63,954 dollars per life-year gained respectively. In comparison with melphalan and prednisone, ASCT appears to be cost-effective in patients 65 years old or younger with myeloma.

Adult↗

PubMed2003

Cost analysis of endoscopic antireflux procedures: endoluminal plication vs. radiofrequency coagulation vs. treatment with a proton pump inhibitor.

BACKGROUND: Both endoluminal gastroplication and radiofrequency coagulation of the lower esophageal sphincter and gastroesophageal junction (Stretta procedure) represent emerging endoscopic therapies for GERD. The economic impact of endotherapy for GERD has not been described. The aim of this study was to apply a decision analysis model to compare the costs of endoluminal gastroplication vs. the Stretta procedures vs. a proton pump inhibitor for treatment of GERD. A cost minimization approach was used. METHODS: Model entry criteria were GERD responsive to daily or twice daily administration of a proton pump inhibitor. Performance characteristics of endotherapy were determined from published data. The baseline probabilities for annual endotherapy failure rates (20%), partial failure rates (10%), and complication rates (1%) were varied through a plausible range by using sensitivity analysis. Cost data for endotherapy were calculated from per case instrumentation costs plus professional fees plus facility fees for ambulatory patient classification codes; cost of treatment with a proton pump inhibitor was based on national average wholesale price. The endpoint was sustained resolution of GERD symptoms. RESULTS: In patients requiring twice daily use of a proton pump inhibitor for symptom relief, endotherapy proves to be the most economical strategy after 17 months. If uniform endotherapy failure rates over time are assumed, medication regains superiority after 29 months. Sensitivity analysis revealed that a proton pump inhibitor remains the most economical option beyond 3 years, provided annual endotherapy failure rates remain greater than 20% (endoluminal gastroplication) or 19% (Stretta). Pharmacotherapy is the least costly approach, irrespective of time, if the daily cost of a proton pump inhibitor is less than $140 a month or endotherapy costs more than $3400. For patients in whom symptoms are relieved with once daily dosing with a proton pump inhibitor, medication remains the most economical option regardless of endotherapy failure rate. CONCLUSION: Endotherapy appears to offer an economical treatment option for patients requiring a proton pump inhibitor twice daily, with its cost superiority enduring for 2.5 years. More long-term follow-up data are required to determine the durability of the endotherapy benefit over time.

Catheter Ablation↗

PubMed1991

Cost-effectiveness of HA-1A monoclonal antibody for gram-negative sepsis. Economic assessment of a new therapeutic agent.

OBJECTIVE: To assess the cost-effectiveness of the HA-1A monoclonal antibody for the treatment of gram-negative bacteremia. DESIGN: Cost-effectiveness analysis of a randomized, double-blind, placebo-controlled trial using clinical efficacy data reported in the medical literature. SETTING: Hospitalized patients with sepsis. PATIENTS: 543 patients with sepsis and suspected gram-negative infection. Patients enrolled in the study met strict criteria for sepsis, including fever or hypothermia (less than 35.6 degrees C or greater than 38.3 degrees C), tachycardia (greater than 90 beats per minute), tachypnea (greater than 20 breaths per minute), and hypotension or two of six signs of systemic toxicity. INTERVENTION: HA-1A vs placebo in addition to usual care. MAIN OUTCOME MEASURES: We determined the range of possible cost-effectiveness ratios for HA-1A therapy, using modeling techniques when clinical or economic variables were unknown. We subjected the model to rigorous sensitivity analysis. We calculated the incremental cost of care and years of life saved for patients with sepsis and modeled two different treatment strategies: treat all patients with sepsis or test and then treat only patients with positive test results. $24,100 per year of life saved based on the treat strategy and $14,900 based on the test strategy. In sensitivity analysis the ratios ranged from $5200 to $110,200 per year of life gained. Annual costs of care for these two strategies are $1.3 billion for the test strategy and $2.3 billion for the treat strategy. CONCLUSION: Economic assessment of new technologies early in their development can be used to guide their efficient clinical introduction.

Antibodies, Monoclonal↗

PubMed2000

Reduced or modified dietary fat for prevention of cardiovascular disease.

BACKGROUND: Reduction or modification of dietary fat can improve total cholesterol levels, but may also have a variety of effects, both positive and negative, on other cardiovascular risk factors. OBJECTIVES: The aim of this systematic review was to assess the effect of reduction or modification of dietary fats on total and cardiovascular mortality and cardiovascular morbidity over at least 6 months, using all available randomized clinical trials. SEARCH STRATEGY: The Cochrane Library, MEDLINE, EMBASE, CAB Abstracts, CVRCT registry and related Cochrane Groups' trial registers were searched through spring 1998, SIGLE to January 1999. Trials known to experts in the field and biographies were included through May 1999. SELECTION CRITERIA: Trials fulfilled the following criteria: 1) randomized with appropriate control group, 2) intention to reduce or modify fat or cholesterol intake (excluding exclusively omega-3 fat interventions), 3) not multi factorial, 4) healthy adult humans, 5) intervention at least six months, 6) mortality or cardiovascular morbidity data available. Inclusion decisions were duplicated, disagreement resolved by discussion or a third party. DATA COLLECTION AND ANALYSIS: Rate data were extracted by two independent reviewers and meta-analysis performed using random effects methodology. Meta-regression and funnel plots were used. MAIN RESULTS: Twenty seven studies were included (40 intervention arms, 30,901 person-years). There was no significant effect on total mortality (rate ratio 0.98, 95% CI 0.86 to 1.12), a trend towards protection form cardiovascular mortality (rate ratio 0.91, 95% CI 0. 77 to 1.07), and significant protection from cardiovascular events (rate ratio 0.84, 95% CI 0.72 to 0.99). The latter became non-significant on sensitivity analysis. Trials where participants were involved for more than 2 years showed significant reductions in the rate of cardiovascular events and a suggestion of protection from total mortality. The degree of protection from cardiovascular events appeared similar in high and low risk groups, but was statistically significant only in the former. REVIEWER'S CONCLUSIONS: The findings are suggestive of a small but potentially important reduction in cardiovascular risk in trials longer than two years. Lifestyle advice to all those at high risk of cardiovascular disease (especially where statins are unavailable or rationed), and to lower risk population groups, should continue to include permanent reduction of dietary saturated fat and partial replacement by unsaturates.

Cardiovascular Diseases↗

PubMed1993

Assessment of costs and benefits of drug therapy for treatment-resistant schizophrenia in the United Kingdom.

An analysis was conducted on the basis of available data to assess the economic consequences of clozapine therapy for people with moderate to severe schizophrenia in long-stay institutions or staffed group homes, with a view to providing an estimate of the likely costs and benefits of the drug. Data from a cost-effectiveness study conducted in the US, supplemented by other literature sources, were used to construct a clinical decision tree for likely clinical outcomes for such patients. A panel of UK psychiatrists provided consensus on how these patients would have been managed in the UK. The costs associated with each patient outcome were estimated, and a sensitivity analysis performed to test the assumptions made. For the patients themselves, clozapine would lead to a net gain of 5.87 years of life with no disability or only mild disability. The base case analysis showed that the direct costs of using clozapine were 91 pounds less per annum (or 1333 pounds per lifetime) than for standard neuroleptic therapy, when the effect on all health-care resources was taken into account. In addition, the sensitivity analysis showed that clozapine would be cost-saving or cost-neutral under many different assumptions. A prospective health economic study with clozapine in the management of schizophrenia would be desirable to confirm these results.

Adult↗

PubMed2002

Benefit of population-based screening for phenotypic hemochromatosis in young men.

BACKGROUND: Hereditary hemochromatosis (HH) is a common genetic disease leading to accumulation of iron in the body, most notably in the liver. More men than women become clinically ill. The prognosis is excellent if phlebotomy treatment is started before liver cirrhosis develops. Screening has been recommended, but the benefit of population-based screening has never been shown in a randomized clinical trial. In this article, we estimate the benefit of screening young men, using a theoretical model. METHODS: A phenotypic screening scenario was modelled using a decision tree. Gain of quality-adjusted life-years was used as a measure of benefit, and estimated using Markov processes. Data on the accuracy of the screening tests, the prevalence of HH and the risk of liver cirrhosis were mainly derived from a cross-sectional study on the prevalence and morbidity of HH in 30509 men. Data on the excess mortality of cirrhosis were taken from relevant literature. Sensitivity analysis was done for important variables. RESULTS: Assuming basal case values for variables, screening a cohort of 1000 men aged 30 years for phenotypic HH would gain about 8 quality-adjusted life-years, compared to awaiting symptomatic disease. Based on actual costs of our cross-sectional study, the screening cost was US$250 per quality-adjusted life-year gained. The prevalence of phenotypic HH, the excess mortality of liver cirrhosis, the quality of life in non-cirrhotic HH patients, and the fractions of patients compliant with treatment were the most important variables in the sensitivity analysis. CONCLUSION: Incorporating screening for phenotypic HH in health survey programmes for young men may be worthwhile.

Adult↗

PubMed2005

Minimizing complications from nonsteroidal antiinflammatory drugs: cost-effectiveness of competing strategies in varying risk groups.

OBJECTIVE: To appraise the cost-effectiveness of competing therapeutic strategies in patient cohorts eligible for aspirin prophylaxis with varying degrees of gastrointestinal (GI) and cardiovascular risk. METHODS: Cost-effectiveness and cost-utility analyses were performed to evaluate 3 competing strategies for the management of chronic arthritis: 1) a generic nonselective nonsteroidal antiinflammatory drug (NSAID(NS)) alone; 2) NSAID(NS) plus a proton pump inhibitor (PPI); and 3) a cyclooxygenase 2-selective inhibitor (coxib) alone. Cost estimates were from a third-party payer perspective. The outcomes were incremental cost per ulcer complication avoided and incremental cost per quality-adjusted life year (QALY) gained. Sensitivity analysis was performed to evaluate the impact of varying patient GI risks and aspirin use. RESULTS: In average-risk patients, the NSAID(NS) + PPI strategy costs an incremental 45,350 US dollars per additional ulcer complication avoided and 309,666 US dollars per QALY gained compared with the NSAID(NS) strategy. The coxib strategy was less effective and more expensive than the NSAID(NS) + PPI strategy. Sensitivity analysis revealed that the NSAID(NS) + PPI strategy became the dominant approach in patients at high risk for an NSAID adverse event (i.e., patients taking aspirin with > or =1 risk factor for a GI complication). CONCLUSION: Generic nonselective NSAIDs are most cost-effective in patients at low risk for an adverse event. However, the addition of a PPI to a nonselective NSAID may be the preferred strategy in patients taking aspirin or otherwise at high risk for a GI or cardiovascular adverse event.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1998

Costs of predicting IDDM.

Programmes aiming at prediction and prevention of insulin-dependent diabetes mellitus (IDDM), a multifactorial autoimmune disease, have been launched or are in the planning phase in several countries. We hypothesized that the costs of finding the correct target subjects for preventive interventions are likely to vary markedly according to the prediction strategy chosen. Average direct costs accruing in the Finnish IDDM Prediction and Prevention Project (DIPP) were analysed from the health care provider's viewpoint. The genetically targeted strategy included costs of assessing genetic IDDM susceptibility followed by measurement of marker(s) of islet autoimmunity in the susceptibility restricted population at 3 to 6-month intervals. In the pure immunological strategy markers of autoimmunity were repeatedly analysed in the entire population. The data were finally exposed to sensitivity analysis. The genetically targeted prediction strategy is cost-saving in the first year if autoimmune markers are analysed as frequently as under the DIPP project, and in all circumstances later. The 10-year direct costs per child are US$ 245 (present value $ 217, 5% discount rate) if the genetically targeted approach is used and $ 733 (present value $ 619) if the pure immunological strategy is chosen. In sensitivity analysis the 10-year costs (present value) per child of the genetically targeted strategy and of the pure immunological strategy varied from $ 152 to $ 241 and from $ 430 to $ 788, respectively. The genetically targeted IDDM prediction strategy is remarkably cost-saving as compared with the pure immunological strategy mainly because fewer subjects will need retesting during the follow-up.

Administration, Intranasal↗

PubMed2000

A comparative analysis of the cost-effectiveness of treatment based on parasitological and symptomatic screening for Schistosoma mansoni in Burundi.

OBJECTIVES: To assess the cost-effectiveness of three alternative screening strategies in delivering treatment to patients presenting with symptoms suggestive of S. mansoni, using data collected from 17 PHCCs in the Rusizi Plain, Burundi. The three strategies were: (1) screening all symptomatic patients using a Kato-Katz smear and treating only the ones found positive; (2) treating all symptomatic patients or (3) treating only those presenting with symptoms of severe diarrhoea (blood in stool). METHODS: The database consisted of 41 051 visits of symptomatic patients to the 17 PHCCs during 1990. Effectiveness was measured as the number of infected patients treated (gold standard: 25-mg Kato-Katz smear). Cost-effectiveness ratios (CERs) (cost in US$ per infected patient treated) were used to compare the control strategies. Sensitivity analysis was performed to assess the effect of drug price and prevalence of infection on the CERs. RESULTS: The overall prevalence of S. mansoni infection was 9.5% (95% CI = 9.1%, 9.9%). Treating only those with severe symptoms of infection would have left 92% of infected patients untreated. Performing a Kato-Katz smear to confirm the diagnosis was more cost-effective than treating all symptomatic patients on a presumptive basis, with CERs of 4.2 US$ and 12.43 US$ per infected person treated, respectively. Sensitivity analysis showed that, for a cost of 0.99 US$ per dose of praziquantel, the Kato-Katz option remained the most cost-effective approach for prevalences under 76%. For a drug price of 0.21 US$ per dose, both strategies would have become equivalent. The latter value varied extensively per PHCC (range 0.17 US$ to 0.51 US$), due to the different prevalences of infection (range 0.5% to 34.3%). CONCLUSION: We found that using severe diarrhoea as an indicator for infection was not appropriate, and that screening symptomatic patients with the Kato-Katz method remained the most cost-effective approach in the given setting. The CER of treating all symptomatic patients on a presumptive basis depended very much on the drug price and the endemic level.

Adolescent↗

PubMed2005

Classification of emergency department chief complaints into 7 syndromes: a retrospective analysis of 527,228 patients.

STUDY OBJECTIVE: Electronic surveillance systems often monitor triage chief complaints in hopes of detecting an outbreak earlier than can be accomplished with traditional reporting methods. We measured the accuracy of a Bayesian chief complaint classifier called CoCo that assigns patients 1 of 7 syndromic categories (respiratory, botulinic, gastrointestinal, neurologic, rash, constitutional, or hemorrhagic) based on free-text triage chief complaints. METHODS: We compared CoCo's classifications with criterion syndromic classification based on International Classification of Diseases, Ninth Revision (ICD-9) discharge diagnoses. We assigned the criterion classification to a patient based on whether the patient's primary diagnosis was a member of a set of ICD-9 codes associated with CoCo's 7 syndromes. We tested CoCo's performance on a set of 527,228 chief complaints from patients registered at the University of Pittsburgh Medical Center emergency department (ED) between 1990 and 2003. We performed a sensitivity analysis by varying the ICD-9 codes in the criterion standard. We also tested CoCo on chief complaints from EDs in a second location (Utah). RESULTS: Approximately 16% (85,569/527,228) of the patients were classified according to the criterion standard into 1 of the 7 syndromes. CoCo's classification performance (number of cases by criterion standard, sensitivity [95% confidence interval (CI)], and specificity [95% CI]) was respiratory (34,916, 63.1 [62.6 to 63.6], 94.3 [94.3 to 94.4]); botulinic (1,961, 30.1 [28.2 to 32.2], 99.3 [99.3 to 99.3]); gastrointestinal (20,431, 69.0 [68.4 to 69.6], 95.6 [95.6 to 95.7]); neurologic (7,393, 67.6 [66.6 to 68.7], 92.7 [92.6 to 92.8]); rash (2,232, 46.8 [44.8 to 48.9], 99.3 [99.3 to 99.3]); constitutional (10,603, 45.8 [44.9 to 46.8], 96.6 [96.6 to 96.7]); and hemorrhagic (8,033, 75.2 [74.3 to 76.2], 98.5 [98.4 to 98.5]). The sensitivity analysis showed that the results were not affected by the choice of ICD-9 codes in the criterion standard. Classification accuracy did not differ on chief complaints from the second location. CONCLUSION: Our results suggest that, for most syndromes, our chief complaint classification system can identify about half of the patients with relevant syndromic presentations, with specificities higher than 90% and positive predictive values ranging from 12% to 44%.

Bayes Theorem↗

PubMed1988

HPLC enrichment of hydrophobic DNA--carcinogen adducts for enhanced sensitivity of 32P-postlabeling analysis.

The sensitivity of 32P-postlabeling analysis for the quantitation of DNA-carcinogen adducts can be sharply increased by enriching adducted nucleotides relative to normal nucleotides in digested DNA samples prior to postlabeling. Normal and adducted nucleotides from benzo[a]pyrene-adducted DNA were injected onto a reverse phase HPLC column. Normal nucleotides were eluted with 5% methanol, 95% 1 M ammonium formate, pH 3.5. Hydrophobic adducted nucleotides were then recovered from the column using either a linear gradient of methanol (to fractionate adducts) or a step gradient of methanol to elute all hydrophobic adducts in one fraction. Recovered chromatographic fractions were dried, postlabeled with 32P, and aromatic DNA--carcinogen adducts were detected and quantitated using TLC on polyethyleneimine cellulose. Results from the HPLC adduct enrichment procedure were generally similar to those from an alternative enrichment scheme utilizing nuclease P1 to selectively dephosphorylate normal nucleotides. HPLC and nuclease P1 procedures are easily combined for the dual analysis of DNA samples from organisms exposed to environmental carcinogens.

Adenosine Triphosphate↗

PubMed2026

Distal versus proximal radial access for diagnostic cerebral angiography: comparative outcomes and learning curve analysis.

BACKGROUND AND PURPOSE: Distal transradial access (dTRA) is an alternative to proximal transradial access (pTRA) for neuroangiography, but comparative real-world data and evidence on its early learning curve remain limited. We compared procedural performance and access-site complications between dTRA and pTRA and evaluated the early learning curve of dTRA. METHODS: We retrospectively analyzed 470 diagnostic cerebral angiography procedures, representing 421 unique patients, performed via radial access at a single center between January 2025 and February 2026, including 237 dTRA and 233 pTRA procedures. Baseline characteristics, including age, sex, body mass index (BMI) category, aortic arch type, and antiplatelet/anticoagulant use, procedural performance, and clinically assessed access-site events were compared between groups. Radial artery occlusion (RAO) was assessed by postoperative bedside pulse examination and confirmed with Doppler ultrasound when clinical findings were uncertain. Multivariable logistic regression was used to evaluate predictors of RAO, persistent bleeding or repeated compression, hand edema, and a composite access-site event endpoint. Because repeated procedures occurred in a subset of patients and event counts were limited, first-procedure sensitivity analysis and analyses of infrequent outcomes were interpreted cautiously. The dTRA learning process was assessed in the first 100 dTRA cases performed by a single operator using multivariable regression, cumulative sum (CUSUM) analysis, segmented trend analysis, and phase-based comparisons. RESULTS: Baseline characteristics were comparable between groups, including age, male sex, BMI category, aortic arch type, and antiplatelet/anticoagulant use. Compared with pTRA, dTRA was associated with more puncture attempts (3.0 [2.0-4.0] vs 2.0 [1.0-3.0], P < 0.001), longer puncture time (2.0 [1.0-5.0] vs 2.0 [1.0-3.0] min, P = 0.003), lower first-pass success (19.4% vs 35.2%, P < 0.001), and a higher crossover rate (11.4% vs 6.0%, P = 0.037). However, dTRA was associated with a lower clinically assessed RAO rate (2.5% vs 7.7%, P = 0.011). On multivariable analysis, pTRA was independently associated with higher odds of RAO (OR 3.27, 95% CI 1.26-8.49, P = 0.015) and the composite access-site event endpoint (OR 3.12, 95% CI 1.55-6.28, P = 0.001). Similar findings were observed in a sensitivity analysis restricted to the first procedure per patient. In the first 100 dTRA cases, cumulative dTRA experience was independently associated with shorter total procedure time (beta = -0.074 min/case, P = 0.009), while CUSUM and moving-average analyses suggested that the major learning effect occurred within approximately the first 10-15 cases. CONCLUSIONS: In this retrospective single-operator cohort, dTRA was associated with lower clinically assessed RAO than pTRA despite greater access difficulty. The early learning effect was mainly reflected in shorter total procedure time. These findings support the feasibility of dTRA but should be interpreted cautiously given the study's observational design and limited anatomical data.

Humans↗

PubMed2005

Invasive group A streptococcal disease: race, hypotension, and immunogenetics.

OBJECTIVE: To determine if there was an association between race and the incidence of hypotension among patients hospitalized for invasive group A streptococcal disease (IGASD). DESIGN: Data were obtained from a retrospective cohort study of IGASD patients. The subjects were hospitalized throughout Florida for IGASD between 1996 and 2000 (N=151). The exposure variable for the current study was race (African Americans, Caucasians). The binary outcome was the presence of hypotension within 48 hours of hospital admission. A sensitivity analysis was performed to determine if a particular human leukocyte antigen (HLA) class II haplotype (DRB1*1501/DQB1*0602) confounded the association between race and the risk of hypotension. IGASD patients possessing this haplotype are less likely to experience hypotension with multiple organ failure. RESULTS: We found that Caucasians had three times the odds of developing hypotension than African Americans (adjusted odds ratio=3.02, 95% confidence interval: 1.10-8.29, P=.03). The sensitivity analysis revealed that the HLA class II haplotype DRB1*1501/DQB1*0602 was most likely not a confounder. CONCLUSIONS: Caucasians were significantly more likely than African Americans to develop the adverse outcome of hypotension within 48 hours of being hospitalized for IGASD. This excess risk is most likely not due to a particular host genetic factor, the HLA class II haplotype DRB1*1501/DQB1*0602.

Black or African American↗

PubMed2000

Using economic evaluations to make formulary coverage decisions. So much for guidelines.

BACKGROUND: It is mandatory for drug manufacturers requesting formulary inclusion under the British Columbia (BC) provincial drug plan to submit a pharmacoeconomic analysis according to published guidelines. These submissions are reviewed by the Pharmacoeconomic Initiative (PI) of BC. OBJECTIVE: To assess the compliance of submitted studies with specific criteria outlined in the guidelines, to assess the methodological quality of individual submissions, and to demonstrate the importance of submitting guidelines-compliant pharmacoeconomic analyses. DATA AND METHODS: All submissions between January 1996 and April 1999 assessed by the PI of BC were included. Submissions were reviewed according to a checklist to establish compliance with respect to choice of comparator drug, study perspective, sensitivity analysis, analytical horizon and discounting. Submissions were examined for association between analytical technique and author, and between source of submission and compliance. Association between compliance and recommendation for approval was also examined. RESULTS: 95 applications were reviewed. Seven submitted no analyses. There were 25 cost-comparison/consequence, 14 cost-effectiveness, 11 cost-minimisation, 9 cost-utility/benefit and 29 budget-impact analyses. 65 of these 88 submissions failed to comply with guidelines. Of these, 45% used an inappropriate comparator drug, 61% lacked a sensitivity analysis, 73% used a third-party payer and excluded a societal perspective, 66% did not provide a long term evaluation and 25% did not specify any time horizon. 80% of noncompliant studies were cost-comparison/consequence or budget-impact analyses (p < 0.001, Fisher's Exact). Of 25 cost-comparison/consequence and 29 budget-impact analyses, 19 (76%) and 24 (83%), respectively, were industry-conducted, whereas cost-effectiveness (11 of 14) and cost-utility/benefit (6 of 9) analyses were mostly subcontracted to private consultants or academics (p < 0.001, Fisher's Exact). 74% of all submissions (compliant and noncompliant) were not recommended by the PI for listing as a provincial drug plan benefit, 16% received approval for restricted benefit and 9% were recommended as full benefit. 80% of the noncompliant submissions were not recommended (p = 0.06, Fisher's Exact test). Moreover, a strong association between type of analysis and type of recommendation was found (p = 0.03, Fisher's Exact test). Cost-comparison/consequence and budget-impact analyses were less likely to be recommended. IMPLICATIONS OF FINDINGS: Our findings show poor compliance with guidelines, especially among industry-conducted studies. Possible explanations are lack of expertise in pharmacoeconomics and/or scepticism regarding the importance of guidelines and submission quality in decision making. As corroborated by the strong associations between type of recommendation and compliance, and between type of recommendation and type of analysis, these 2 characteristics have a significant impact on decision making.

British Columbia↗

PubMed2001

Incremental cost analysis of ambulatory clinic and home-based intravenous therapy for patients with multiple myeloma.

BACKGROUND: Patients with multiple myeloma and other forms of cancer receiving pamidronate via intravenous (IV) infusion at the Hamilton Regional Cancer Centre in Hamilton, Ontario, Canada face 2 treatment options: they can have their entire treatment completed at the clinic using traditional IV therapy (e.g. IV bag and pole) or they can have the treatment initiated at the clinic and then return home to complete the treatment utilising a portable and disposable IV therapy device. OBJECTIVE: To perform a cost analysis of these 2 treatment options. PERSPECTIVE: Societal. METHODS AND PATIENTS: Data on all patients with multiple myeloma who attended the Hamilton Regional Cancer Centre for pamidronate therapy from November 1, 1997 to October 31, 1998 were collected from clinic records. As almost all of these patients with multiple myeloma completed their IV therapy at home, comparison to clinic-based therapy was based on derived cost estimates. Cost data, where possible, were acquired from the Hamilton Regional Cancer Centre's records. A sensitivity analysis was also conducted. RESULTS: In the base-case scenario for the study period, the incremental cost of the infusion device and training in Canadian dollars ($Can; 1998 values) for the 48 patients (299 cycles) who had their infusion initiated at the clinic but completed at home was $Can 5.50/cycle ($Can 4,636 for the 299 cycles). If these 48 patients had had their entire infusion at the clinic, the incremental costs of overtime treatment, parking, clinic overheads and lost work or leisure time would have been $Can 68.49/cycle ($Can 20,477 for the 299 cycles). Therefore, shifting treatment from the clinic to the home resulted in net cost savings to society of $Can 52.98/cycle ($Can 15,841 for the 299 cycles). Sensitivity analysis of best- and worst-cost scenarios did not alter the substantive findings although the relative difference between treatment options varied. In the best-case scenario, home treatment was $Can 95.97/cycle ($Can 28,696 for the 299 cycles) less costly than clinic treatment, while in the worst-case scenario, home treatment was $Can 17.19/cycle ($Can 5,141 for the 299 cycles) less costly than clinic treatment. The results also demonstrated that clinic overheads, the cost of a portable and disposable infusion device and the cost of lost work and leisure time had the greatest impact on incremental costs for each treatment option. CONCLUSION: Subject to study limitations, a significant cost advantage was demonstrated through the home-based treatment option for patients with multiple myeloma. Key issues that must be addressed in future evaluations include the precise determination of clinic overheads, the valuation of lost work and/or leisure time and the direct cost of portable and disposable infusion devices.

Aged↗

PubMed1987

Role of the fourth complement component (C4) in the regulation of contact sensitivity. I. Analysis in mice with high and low C4 levels.

Lymph node cells collected from CBA/J mice 4 days after painting the skin with picryl chloride are able to immunize naive recipients by hapten-IgM immuno complexes. These cells ("4-day" cells) activate the early components of the classical pathway of complement from mice of the H-2 Sd haplotype (high-C4), but fail to activate the classical pathway of complement from mice of the H-2 Sk haplotype (low-C4). Incubation of "4-day" cells in complement from mice with high-C4 levels abolishes the induction of contact sensitivity, probably as a consequence of the solubilization of membrane-bound immuno complexes caused by complement activation. The presence of "4-day" cells is determined by the levels of C4. In fact, using strains of mice which differ only at the S region of the H-2 complex, we found that mice of the H-2 Sd (and perhaps H-2 Sb) haplotype (high-C4 levels) lack "4-day" cells in their lymph nodes and this is due to the activation of the early components of the classical complement pathway which occurs in vivo in these mice during sensitization with picryl chloride. The finding that contact sensitivity reaction to picryl chloride in H-2 Sk mice lasts about 21 days, whereas H-2 Sd mice show a contact sensitivity reaction until 7 days after sensitization, strongly suggests that the S region, and in particular C4 levels, controls the persistence of "4-day" immunogenic cells, and so play a role in the duration of the contact sensitivity reaction to picryl chloride in the mouse.

Animals↗

PubMed2001

Timing of antiretroviral therapy. Use of Markov modeling and decision analysis to evaluate the long-term implications of therapy.

BACKGROUND: The timing of initiation of antiretroviral therapy is controversial. Current guidelines are heavily based on the principle of 'hit early, hit hard', although the long-term implications of this approach are unknown. METHODS: Using Markov modeling and decision analysis we modeled the virologic outcomes over 10 years in a hypothetical population of 10 000 HIV-infected patients in which therapy (with the possibility of three sequential regimens before the development of multidrug-resistant virus) is started immediately versus starting progressively at rates of 5, 10, 15, 20 or 30% of the original population each year. The model used inputs from available clinical trial data: virologic success rate and durability of the response of the first and subsequent regimens. We performed one-way and two-way sensitivity analysis to evaluate changes in the input variables. RESULTS: If therapy is started immediately in all patients, by 10 years 57% would be undetectable, but 38% would have detectable multidrug-resistant virus. In contrast, the population as a whole would have had better virologic outcomes if one waited before starting treatment at any progression rate; for example, initiating therapy in 10% of the subjects per year results in 64% of patients being undetectable and 24% with multidrug-resistant virus. Two-way sensitivity analysis demonstrates that immediate initiation should be at least 15 to 20% better than delayed antiretroviral therapy to justify immediate initiation of therapy over a wide range of success rates of the delayed start. CONCLUSION: Our analysis, utilizing optimistic outcomes based on short-term clinical trials, provides a theoretical basis for questioning the current aggressive early use of therapy and should help prompt studies that look at when and how to start antiretroviral therapy.

Anti-HIV Agents↗

PubMed2006

The McKenzie method for low back pain: a systematic review of the literature with a meta-analysis approach.

STUDY DESIGN AND OBJECTIVES: Meta-analysis of randomized controlled trials to evaluate the effectiveness of the McKenzie method for low back pain (LBP). SUMMARY OF BACKGROUND DATA: The McKenzie method is a popular classification-based treatment for LBP. The faulty equation of McKenzie to extension exercises (generic McKenzie) is common in randomized trials. METHODS: MEDLINE, EMBASE, PEDro, and LILACS were searched up to August 2003. Two independent reviewers extracted the data and assessed methodologic quality. Pooled effects were calculated among homogeneous trials using the random effects model. A sensitivity analysis excluded trials reporting on generic McKenzie. RESULTS: Eleven trials of mostly high quality were included. McKenzie reduced pain (weighted mean difference [WMD] on a 0- to 100-point scale, -4.16 points; 95% confidence interval, -7.12 to -1.20) and disability (WMD on a 0- to 100-point scale, -5.22 points; 95% confidence interval, -8.28 to -2.16) at 1 week follow-up when compared with passive therapy for acute LBP. When McKenzie was compared with advice to stay active, a reduction in disability favored advice (WMD on a 0- to 100-point scale, 3.85 points; 95% confidence interval, 0.30 to 7.39) at 12 weeks of follow-up. Heterogeneity prevented pooling of studies on chronic LBP as well as pooling of studies included in the sensitivity analysis. CONCLUSIONS: There is some evidence that the McKenzie method is more effective than passive therapy for acute LBP; however, the magnitude of the difference suggests the absence of clinically worthwhile effects. There is limited evidence for the use of McKenzie method in chronic LBP. The effectiveness of classification-based McKenzie is yet to be established.

Acute Disease↗