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Efficacy Data (efficacy + data)
Selected AbstractsThe influence of concurrent anticonvulsants on the efficacy of the ketogenic dietEPILEPSIA, Issue 8 2009Peter F. Morrison Summary It is unknown if any particular anticonvulsants modify the likelihood of seizure reduction when used in combination with the ketogenic diet (KD). A retrospective study was performed of 217 consecutive children who started the KD from 2000,2007. Patients included did not have any changes to their anticonvulsant dose. Efficacy data at 3 months on the KD were analyzed with respect to the six most frequently used anticonvulsants in this cohort. A total of 115 patients were included. Children receiving phenobarbital in combination with the KD were significantly less likely to have a >50% seizure reduction (p = 0.003). Conversely, those receiving zonisamide in combination with the KD at onset were more likely to have a >50% reduction (p = 0.04). These results provide practical information to clinicians who are treating children receiving both the KD and anticonvulsants. [source] Cost-effectiveness of psoriasis therapy with etanercept in GermanyJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 9 2007Tatjana Heinen-Kammerer Summary Background: We estimated the cost-effectiveness of intermittent therapy with etanercept in patients with moderate-to-severe plaque-type psoriasis in comparison to non-systemic therapy in Germany. Patients and Methods: We performed a cost-utility analysis using the endpoint costs per quality-adjusted life year gained (costs/QALY). For this purpose, we adapted a UK-based Markov model by means of resource use data that we derived from a German cost study. Efficacy data, information on frequency of adverse events and changes in quality of life were derived from three pooled clinical trials. We extrapolated the further course of the disease and its treatment over a 10 year course. Results: For patients with an initial Psoriasis Area and Severity Index (PASI) > 10 and a Dermatology Life Quality Index (DLQI) > 10 the incremental cost-effectiveness ratio (ICER) for etanercept compared to non-systemic therapy was 45,491 ,/QALY. For patients with PASI and DLQI > 15 costs/QALY were 32,058 , and among patients with severe plaque psoriasis (DLQI and PASI > 20) 18,154 , . Conclusions: According to internationally accepted levels of cost-effectiveness thresholds, the intermittent treatment of (moderate to) severe plaque-type psoriasis with etanercept is a cost-effective measure within the German healthcare system. [source] Older age predicts a decline in adjuvant chemotherapy recommendations for patients with breast carcinomaCANCER, Issue 9 2003Evidence from a tertiary care cohort of chemotherapy-eligible patients Abstract BACKGROUND The appropriate use of adjuvant chemotherapy for elderly women with breast carcinoma remains controversial. Efficacy data in women age , 70 years are scarce, resulting in a lack of clear guidelines for patients in this age group. Although several studies have demonstrated decreasing use of chemotherapy with age, none specifically examined its use in an elderly cohort of patients who were deemed eligible for such therapy based on consensus guidelines, simultaneously examining the impact of comorbidity and previous history of malignant disease on these recommendations. METHODS The authors examined adjuvant chemotherapy use among chemotherapy-eligible patients age , 50 years who were evaluated in a tertiary care cancer center. Associations between patient age and 1) physician recommendation for adjuvant chemotherapy, 2) recommended treatment regimen, and 3) patient acceptance of the treatment plan recommended were examined, adjusting for the impact of aggressive tumor characteristics, medical comorbidity, previous history of malignant disease, and features of the treatment setting. RESULTS Of the 208 chemotherapy-eligible patients who were studied, 74% overall were recommended chemotherapy. Chemotherapy was recommended to 92% of women age 50,59 years compared with 77% of women age 60,69 years and 23% of women age , 70 years. Increasing age was associated strongly with a decreasing likelihood of receiving a recommendation in favor of chemotherapy. After adjusting for estrogen receptor status, previous history of malignant disease, comorbidity score, and prognostic group, the odds of receiving a recommendation in favor of chemotherapy fell by 22% per year or 91% per 10-year interval, and the rate of decline did not change significantly at age , 70 years. We found no age-related differences in either the drug regimens recommended or patient acceptance rates for adjuvant therapy. CONCLUSIONS Age was associated strongly and independently with physician recommendation for adjuvant chemotherapy among a group of older women who were eligible specifically for such therapy. Medical comorbidity and a history of previous malignant disease did not alter this correlation significantly, although the latter was a significant predictor of chemotherapy use. Further studies clearly are needed to determine the underlying reasons for this strong age effect and to explore strategies that will optimize the utilization of this potentially curative therapy in the elderly. Cancer 2003;97:2150,9. © 2003 American Cancer Society. DOI 10.1002/cncr.11338 [source] Differentiating members of the thiazolidinedione class: a focus on efficacy,DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue S2 2002Barry J. Goldstein Abstract The thiazolidinediones (TZDs) or ,glitazones' are a new class of drug used for the treatment of type 2 diabetes. Although their precise mechanism of action is not known, TZDs target insulin resistance directly and thus tackle an underlying cause of the disease. Two TZDs are indicated for use in type 2 diabetes in the USA, pioglitazone and rosiglitazone. A third, troglitazone, has been associated with significant hepatotoxicity and has been withdrawn from use. In clinical trials, all three TZDs effectively lower blood glucose levels as monotherapy and in combination therapy with sulfonylureas, metformin and insulin. To date, head-to-head comparative studies with these agents have not been performed. It is difficult, therefore, to make direct comparisons of their efficacy since other variables, including baseline glucose levels and study design, can have a significant impact on treatment outcome. Despite this and in light of unique safety issues characterized with certain TZDs, it is useful to look closely at the efficacy data for these agents. It is not sufficient to assume that ,all glitazones are the same' because the studies have not yet been done to support this statement. This article will review what is known about the relative efficacy of the TZDs. Copyright © 2002 John Wiley & Sons, Ltd. [source] Development of a structured generic drug intervention model for public health purposes: a brief application of motivational interviewing with young peopleDRUG AND ALCOHOL REVIEW, Issue 4 2003JIM MCCAMBRIDGE Abstract Brief applications of Motivational Interviewing (MI) emerged around 15 years ago to target problematic alcohol and other drug use. Interventions which specifically target illicit drug use, young people, or which are delivered in settings other than health-care services have, however, been relatively slow to develop. The needs of young people for interventions distinct from those offered to adults are considered, as a precursor to an outline of the structure of a newly adapted intervention targeting drug use in general among young people. Based upon earlier topic-based approaches developed by Rollnick et al. this intervention is innovative in simultaneously targeting a range of drugs in pursuit of secondary prevention objectives, while also seeking to manifest the spirit of MI. The intervention consists of a single-session face-to-face conversation of up to 60 minutes duration. Data are presented which describe the development and conduct of this intervention during the course of an efficacy trial, with promising efficacy data themselves reported elsewhere. Observations are made on intervention delivery and consideration is given to implications for further novel targeting of young people and within the field of addiction interventions more generally. [source] Long-Term Tolerability of Sumatriptan Nasal Spray in Adolescent Patients With MigraineHEADACHE, Issue 10 2004Shankar Natarajan MD Objective.,This 1-year, open-label, multicenter study was designed to assess the long-term tolerability and efficacy of sumatriptan nasal spray 20 mg in adolescent patients with migraine. Methods.,A prospective, multicenter, open-label study was conducted in patients aged 12 to 17 years who were allowed to treat an unlimited number of migraines at severe, moderate, or mild pain intensity with sumatriptan nasal spray for up to 1 year. All patients started the study at the 20-mg dose of sumatriptan nasal spray. Dose could be adjusted downward to 5 mg at the discretion of the investigator to optimize therapy. Results.,A total of 484 adolescent migraineurs treated 4676 migraines with sumatriptan nasal spray 20 mg (3593 during the first 6 months and 1083 during the second 6 months). A total of 3940 migraines and 699 migraines were treated with one and two 20-mg doses of sumatriptan nasal spray, respectively. Only 10 patients (treating 42 migraines) took the 5-mg dose of sumatriptan nasal spray. The overall percentage of migraines treated with either one 20-mg dose or one, two, or three 20-mg doses with at least 1 drug-related adverse event was 19%. The most common specific drug-related adverse event was unpleasant taste, reported in 17% of migraines. No other single drug-related adverse event was reported in more than 1% of migraines over the 1-year treatment period. When unpleasant taste was excluded from the adverse-event tabulations, the percentages of migraines with at least 1 drug-related adverse event after one or one, two, or three 20-mg doses declined to 4% and 3%, respectively. No patient experienced any drug-related changes in 12-lead ECGs, vital signs, or nasal assessments; and no clinically meaningful changes in clinical laboratory values were observed. Across all migraines with evaluable efficacy data (n = 4334), headache relief was reported in 43% of migraines at 1 hour and in 59% at 2 hours after dosing with sumatriptan nasal spray 20 mg. Of the 2561 migraines with headache relief 2 hours postdose, headache recurrence was reported within 24 hours of initial dosing in 7% of migraines. None of the efficacy or tolerability results varied as a function of time in the study (ie, first 6 months vs. second 6 months). Conclusion.,Sumatriptan nasal spray 20 mg is generally well tolerated and may be beneficial during long-term use by adolescent migraineurs ages 12 to 17 years. [source] Migraine Headache Recurrence: Relationship to Clinical, Pharmacological, and Pharmacokinetic Properties of TriptansHEADACHE, Issue 4 2003Gilles Géraud MD Background and Objectives.,Triptan use is associated with headache recurrence, and this has been cited as an important reason for patient dissatisfaction with the treatment. The mechanism by which recurrence occurs is not clear, and the incidence of recurrence varies with the triptan used. In order to explore the pharmacological and physiological interaction of triptans and migraine headache recurrence further, some specific clinical, pharmacological, and pharmacokinetic factors that might influence migraine recurrence were evaluated in a review of the major efficacy data for the drugs in the triptan class. These factors were 5-HT1B and 5-HT1D receptor activities, the pharmacokinetic elimination half-life of each triptan, and the clinical efficacy of each compound, determined by the proportion of patients with headache relief and the therapeutic gain over placebo. Methods.,Clinical data were derived from 31 triptan, placebo-controlled, major efficacy studies used in a previous meta-analysis. The mean recurrence rate, mean headache response, and therapeutic gain were calculated using the results from the individual clinical studies. Mean headache response and therapeutic gain were calculated at the time point used to define recurrence in each study. Data for binding affinity and potency were taken from a direct-comparison in vitro pharmacology study, and the elimination half-life quoted in the data sheet for each triptan was used. Rank correlation with recurrence rate was performed for each of the test parameters. Results.,Mean headache recurrence rates ranged from 17% for frovatriptan 2.5 mg to 40% for rizatriptan. Elimination half-life and recurrence were inversely correlated (r = ,1.0, P = .0016). There was also a significant inverse correlation between 5-HT1B receptor potency and recurrence (r = ,0.68, P = .034), but 5-HT1D receptor potency was not correlated with recurrence (r = ,0.20, P = .54). In addition, the binding affinities for the 5-HT1B and 5-HT1D receptors were not correlated to headache recurrence. Importantly, it also was demonstrated that initial clinical efficacy was not correlated to headache recurrence. The correlation coefficient for headache response was 0.18 (P = .53) and for therapeutic gain, ,0.11 (P = .71). Conclusion.,The incidence of migraine headache recurrence varies between drugs in the triptan class. Migraine recurrence does not appear to be related to initial clinical efficacy, but is influenced by the pharmacological and pharmacokinetic properties of the individual triptans. The triptans with longer half-lives and greater 5-HT1B receptor potency had the lowest rates of headache recurrence. [source] Antiadhesion molecule therapy in inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 4 2002Dr. Gert Van Assche Abstract Adhesion molecules regulate the influx of leukocytes in normal and inflamed gut. Some of these molecules such as MadCAM-1 are specific for the gastrointestinal endothelium, but in inflammatory bowel diseases most of the adhesion factors are up-regulated. Adhesion molecules also are involved in local lymphocyte stimulation and antigen presentation within the intestinal mucosa. Recently, therapeutic compounds directed against trafficking of lymphocytes toward the gut mucosa have been designed, and are being developed as a novel class of drugs in the treatment of Crohn's disease (CD) and ulcerative colitis. This review deals with the immunological aspects of leukocyte trafficking focused on gut homing of T cells. Secondly, the changes in adhesion molecules and T-cell trafficking during intestinal inflammation are discussed. Finally, we review the clinical data that have been gathered in trials of biological therapies directed against adhesion molecules. Both antiintercellular adhesion molecule-1 (ICAM-1) and anti-,4 integrin strategies are being developed. Trials with the anti-ICAM-1 antisense oligonucleotide, ISIS-2302, in steroid-refractory CD have provided conflicting efficacy data. The anti-,4 integrin antibodies natalizumab (Antegren) and LDP-02 are in phase III and phase II trials, respectively. In the near future, these novel biological agents may prove valuable therapeutic tools in the management of refractory IBD. [source] Outcomes Associated with Opioid Use in the Treatment of Chronic Noncancer Pain in Older Adults: A Systematic Review and Meta-AnalysisJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 7 2010Maria Papaleontiou MD This systematic review summarizes existing evidence regarding the efficacy, safety, and abuse and misuse potential of opioids as treatment for chronic noncancer pain in older adults. Multiple databases were searched to identify relevant studies published in English (1/1/80,7/1/09) with a mean study population age of 60 and older. Forty-three articles were identified and retained for review (40 reported safety and efficacy data, the remaining 3 reported misuse or abuse outcome data). The weighted mean subject age was 64.1 (mean age range 60,73). Studies enrolled patients with osteoarthritis (70%), neuropathic pain (13%), and other pain-producing disorders (17%). The mean duration of treatment studies was 4 weeks (range 1.5,156 weeks), and only five (12%) lasted longer than 12 weeks. In meta-analyses, effect sizes were ,0.557 (P<.001) for pain reduction, ,0.432 (P<.001) for physical disability reduction, and 0.859 (P=.31) for improved sleep. The effect size for the Medical Outcomes Study 36-item Health Survey was 0.191 (P=.17) for the physical component score and ,0.220 (P=.04) for the mental component score. Adults aged 65 and older were as likely as those younger than 65 to benefit from treatment. Common adverse events included constipation (median frequency of occurrence 30%), nausea (28%), and dizziness (22%) and prompted opioid discontinuation in 25% of cases. Abuse and misuse behaviors were negatively associated with older age. In older adults with chronic pain and no significant comorbidity, short-term use of opioids is associated with reduction in pain intensity and better physical functioning but poorer mental health functioning. The long-term safety, efficacy, and abuse potential of this treatment practice in diverse populations of older persons remain to be determined. [source] Regular or "Super-Aspirins"?JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 4 2001A Review of Thienopyridines or Aspirin to Prevent Stroke PURPOSE: To review the evidence for the effectiveness and safety of the thienopyridines (ticlopidine and clopidogrel) compared with aspirin for the prevention of vascular events among patients at high risk of vascular disease. BACKGROUND: Atherosclerosis and resultant cardiovascular disease are important causes of morbidity and mortality in older people. In particular, atherosclerosis of the cerebral arteries can lead to transient ischemic attacks (TIAs) and stroke. Stroke ranks as the third-leading cause of death in the United States and in 1997 was responsible for over 150,000 fatalities.1 In addition to the mortality associated with this disease, stroke is also a leading source of long-term disability in survivors. Nearly 4.5 million stroke survivors are alive today,1 highlighting the fact that primary, but also secondary, prevention are extremely important for minimizing the complications of this illness. DATA SOURCES: Specialized trial registers of the Cochrane Stroke Group and the Antithrombotic Trialist's Collaboration, MEDLINE, and Embase were searched. Additional unpublished information and data were sought from Sanofi, the pharmaceutical company that developed and manufactures ticlopidine and clopidogrel, as well as the principal investigators of the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial,7 the largest of the trials identified. STUDY SELECTION CRITERIA: All unconfounded randomized trials comparing either ticlopidine or clopidogrel with aspirin among patients at high risk of vascular disease (those with symptoms of ischemia of the cerebral, coronary, or peripheral circulations) who were followed for at least 1 month for the recurrence of vascular events were included. DATA EXTRACTION: Data were extracted from four completed randomized trials completed in the past 20 years, which included 22,656 patients.7,10 Two authors independently extracted the data from these trials for the following information: the types of patients enrolled; the entry and exclusion criteria; the randomization method; the number of patients originally allocated to the treatment and control groups; the method and duration of follow-up; the number of patients in each group lost to follow-up; information on compliance with the treatment allocated; the definitions of outcome events; the number of outcome events in each treatment group; and any method used for blinding patients, treating clinicians, and outcome assessors to treatment allocation. MAIN RESULTS: Four completed trials involving a total of 22,656 patients were identified. Aspirin was compared with ticlopidine in three trials (3,471 patients)8,10 and with clopidogrel in one trial (19,185 patients).7 A recent TIA or ischemic stroke was the qualifying event in 9,840 patients, a recent myocardial infarction in 6,302 patients, and symptomatic peripheral arterial disease in 6,514 patients. The average age of the patients was approximately 63, with approximately two-thirds of the patients being male and white. The duration of follow-up ranged from 12 to 40 months. CONCLUSIONS: This systematic review demonstrates that, compared with aspirin, thienopyridines are only modestly more effective in preventing serious vascular events in high-risk patients. For patients who are intolerant of, or allergic to aspirin, the available safety and efficacy data suggest that clopidogrel is an appropriate, but more-expensive, alternative antiplatelet drug. It appears safer than ticlopidine and as safe as aspirin but it should not replace aspirin as the first-choice antiplatelet agent for all patients. Further studies are necessary to determine which, if any, particular types of patients would benefit most and least from clopidogrel instead of aspirin. [source] Allen Denver Russell Memorial Lecture, 2006JOURNAL OF APPLIED MICROBIOLOGY, Issue 4 2006The use of microbiocides in infection control: a critical look at safety, applications, testing Abstract Microbial pathogens continue as major threats to health. Indeed, many ongoing societal changes are enhancing our vulnerability and exposure to several frank and opportunistic pathogens. This, together with rampant antimicrobial resistance and reduced prospects for newer drugs and vaccines, is forcing a higher reliance on microbiocides in infection prevention and control. That this reliance may not be well-founded becomes apparent from a closer look at current ways of testing and registering microbiocides, their label claims as well as human and environmental safety of certain widely used microbicidal chemicals. Many methods to test microbiocides for registration are flawed and/or entail test conditions irrelevant to field use. Pathogens listed on product labels may not be among those amenable to interruption through microbiocide use. The wide variations and discrepancies in existing national/regional regulations for registering microbiocides for sale stifle innovation. This is a critical look at the above-mentioned issues with emphasis on chemicals meant for use on environmental surfaces and medical devices. It highlights better ways to test microbiocides and to attain global harmonization of testing and product registration. It also details the known and potential dangers of microbiocide use and what to consider in choosing such formulations for optimal safety and effectiveness. End users are advised to be more critical and prudent in the selection and application of microbicidal chemicals, manufacturers are encouraged to explore infection control products and technologies that are safer in the workplace and for the environment, and regulators are urged to review and update the requirements and procedures for premarket review of microbiocide efficacy data and label claims. Independent investigations are also urgently needed to document the proportion of nosocomial infections that would be amenable to prevention through chemical disinfection of environmental surfaces. [source] Efficacy and safety of over-the-counter analgesics in the treatment of common cold and fluJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 4 2006R. Eccles BSc PhD DSc Summary Rationale:, Common cold and flu are the most common human illnesses, and over-the-counter (OTC) analgesics are widely used to treat the pain and fever symptoms. Despite the every day use of these analgesic there is little information available in the literature on the efficacy and safety of these medicines in treating colds and flu symptoms. The aim of this review was to determine the safety and efficacy of the analgesics, aspirin, paracetamol and aspirin for the treatment of colds and flu. Methods:, Electronic databases and a personal database were searched and the information retrieved together with information from relevant textbooks has been integrated in the review. Results:, The literature search established that there is relatively little information on the use of analgesics in treating colds and flu and that much of the safety and efficacy data must be related to other pain and fever models. The review establishes that aspirin, paracetamol and ibuprofen are safe in OTC doses and that there is no evidence for any difference between the medicines as regards efficacy and safety for treatment of colds and flu (except in certain cases such as the use of aspirin in feverish children). There is also no evidence that these medicines prolong the course of colds and flu by any effect on the immune system or by reducing fever. Conclusion:, Despite the lack of clinical data on the safety and efficacy of analgesics for the treatment of colds and flu symptoms a case can be made that these medicines are safe and effective for treatment of these common illnesses. [source] Cost-effectiveness of biological therapy for Crohn's disease: Markov cohort analyses incorporating United Kingdom patient-level cost dataALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009K. BODGER Summary Background, Anti-TNF-alpha agents for Crohn's disease (CD) have good clinical efficacy but high acquisition cost compared to rival drugs. Aim, To assess the cost-effectiveness of infliximab and adalimumab for Crohn's disease from the perspective of the UK NHS, incorporating recent trial and observational data. Methods, Lifetime Markov analyses constructed to simulate quality-adjusted life-years (QALYs) and costs. CD was represented by four health-states representing: Full response, partial response, nonresponse, surgery and death. The course of CD under standard care was based on the Olmsted county cohort. Systematic review identified ACCENT I (infliximab) and CHARM (adalimumab) as sources for efficacy data. We modelled an intention-to-treat strategy for biologics including surgical rates based on observational data, cost estimates from our UK dataset and utilities from an algorithm converting CDAI to EQ-5D utilities. Results, The incremental cost-effectiveness ratios (ICERs) compared to standard care for 1-year of treatment with infliximab or adalimumab were £19 050 and £7190 per QALY gained, respectively. Lifetime therapy was dominated by standard care. Analyses over shorter time horizons, matched to treatment duration, resulted in unfavourable ICERs. Conclusion, The model suggests acceptable ICERs for biological agents when considering a lifetime horizon with periods of up to 4 years continuous therapy. As with all economic evaluations, the results may not be generalizable beyond the perspective of analysis. [source] A phase 2 clinical trial of metformin as a treatment for non-diabetic paediatric non-alcoholic steatohepatitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2005J. B. Schwimmer Summary Background :,Children with non-alcoholic steatohepatitis are insulin-resistant and metformin has been proposed as a potential therapy. However, paediatric safety and efficacy data are absent. Aim :,To test the hypothesis that metformin therapy will safely improve markers of liver disease in paediatric non-alcoholic steatohepatitis. Methods :,Single-arm open-label pilot study of metformin 500 mg twice daily for 24 weeks in non-diabetic children with biopsy-proven non-alcoholic steatohepatitis. Results :,Ten obese children (mean body mass index 30.4) enrolled and completed the trial. Mean alanine aminotransferase and aspartate aminotransferase (AST) improved significantly (P < 0.01) from baseline (184, 114 U/L) to end of treatment (98, 68 U/L). Alanine aminotransferase normalized in 40% and AST normalized in 50% of subjects. Children demonstrated significant improvements in liver fat measured by magnetic resonance spectroscopy (30,23%, P < 0.01); insulin sensitivity measured by quantitative insulin sensitivity check index (0.294,0.310, P < 0.05); and quality of life measured by pediatric quality of life inventory 4.0 (69,81, P < 0.01). Conclusion :,Open-label treatment with metformin for 24 weeks was notable for improvement in liver chemistry, liver fat, insulin sensitivity and quality of life. A large randomized-controlled trial is needed to definitively determine the efficacy of metformin for paediatric non-alcoholic steatohepatitis. [source] A quantitative approach to benefit-risk assessment of medicines , part 1: the development of a new model using multi-criteria decision analysis,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue S1 2007Filip Mussen PhD Abstract Purpose One of the most important uses of benefit-risk assessment pertains to approval of new medicines by regulatory authorities and the subsequent review of these products during their life-cycle when new safety and/or efficacy data becomes available. At present, there exist no validated, well-accepted models for benefit-risk assessment that have the appropriate degree of sophistication, and as a consequence no models are widely used by regulatory authorities or industry. The aim of the study was therefore to develop a new model for benefit-risk assessment of medicines using multi-criteria decision analysis (MCDA). Methods The MCDA methodology was used for a systematic approach to assess the benefit risk ratio of medicines. The reasons for adopting this approach were (1) taking multiple benefit and risk criteria into account, (2) making a judgement on the evidence and potential uncertainty because of the incompleteness of evidence, and (3) making trade-offs of the benefits against risks. Results It was demonstrated through a seven-step approach how MCDA is used to construct the model. Ten benefit and ten risk criteria were identified to form a value tree. Then fixed scales were established for all criteria and options on the criteria were scored. Weights were assigned for each criteria using swing-weighting. Finally sensitivity analysis was carried. Conclusions This novel approach based on MCDA has the potential for being applied as a new tool for judging and deciding on the benefits and risks, thereby helping regulators and industry in the development and approval of new medicines and their adequate use. Copyright © 2007 John Wiley & Sons, Ltd. [source] Improved safety with equivalent asthma control in adults with chronic severe asthma on high-dose fluticasone propionateRESPIROLOGY, Issue 3 2001Norbert Berend Objective: High-dose inhaled corticosteroids (ICS) have been associated with the same side-effects as oral corticosteroids. Beclomethasone dipropionate (BDP) and budesonide (BUD) in doses greater than 2000 ,g/day are used regularly in severe asthma, despite the fact that safety and efficacy data at such high doses are limited. Fluticasone propionate (FP) has been promoted as being twice as potent clinically as BDP or BUD at doses of 2000 ,g/day or less with a similar safety profile. The aim of this study was to compare the efficacy and safety of FP with BDP and BUD in 133 symptomatic adult asthmatics requiring at least 1750 ,g/day of BDP or BUD. Methodology: Patients fulfilling the entry criteria were randomized to receive either their regular ICS medication or FP at approximately half the microgram dose for 6 months in an open, parallel group study. The primary efficacy measure was based on morning peak expiratory flow measurements recorded by patients on daily record cards, while determination of safety was based on a number of endpoints including changes in bone turnover indices, the incidence of topical side-effects and assessments of quality of life. Results: It was shown that patients who were switched to FP, but not those continuing with BDP or BUD, had significant increases in levels of morning serum cortisol and the urine cortisol:creatinine ratio while maintaining asthma control. Serum osteocalcin and the pyridinoline:creatinine ratio, as well as the deoxypyridinoline:creatinine ratio, were also shown to increase only in the FP group. Subjective assessments such as quality of life score, the incidence and ease of bruising, and reports of hoarseness also favoured the FP group. Conclusions: It is concluded that, at the doses studied and with the delivery devices used clinically, FP is at least as effective as BDP/BUD in the management of severe asthma and may offer clinical advantages with respect to steroid-related adverse effects. [source] Determination of Sample Sizes for Demonstrating Efficacy of Radiation CountermeasuresBIOMETRICS, Issue 1 2010Ralph L. Kodell Summary In response to the ever increasing threat of radiological and nuclear terrorism, active development of nontoxic new drugs and other countermeasures to protect against and/or mitigate adverse health effects of radiation is ongoing. Although the classical LD50 study used for many decades as a first step in preclinical toxicity testing of new drugs has been largely replaced by experiments that use fewer animals, the need to evaluate the radioprotective efficacy of new drugs necessitates the conduct of traditional LD50 comparative studies (FDA, 2002,,Federal Register,67, 37988,37998). There is, however, no readily available method to determine the number of animals needed for establishing efficacy in these comparative potency studies. This article presents a sample-size formula based on Student's,t,for comparative potency testing. It is motivated by the U.S. Food and Drug Administration's (FDA's) requirements for robust efficacy data in the testing of response modifiers in total body irradiation experiments where human studies are not ethical or feasible. Monte Carlo simulation demonstrated the formula's performance for Student's,t, Wald, and likelihood ratio tests in both logistic and probit models. Importantly, the results showed clear potential for justifying the use of substantially fewer animals than are customarily used in these studies. The present article may thus initiate a dialogue among researchers who use animals for radioprotection survival studies, institutional animal care and use committees, and drug regulatory bodies to reach a consensus on the number of animals needed to achieve statistically robust results for demonstrating efficacy of radioprotective drugs. [source] Reporting outcomes in clinical trials for bipolar disorder: a commentary and suggestions for changeBIPOLAR DISORDERS, Issue 5 2008Anabel Martinez-Arán Objective:, Newer outcome measures and statistical reporting that better translate efficacy data to evidence-based psychiatric care are needed when evaluating clinical trials for bipolar disorder. Using efficacy studies as illustrations, the authors review and recommend changes in the reporting of traditional clinical outcomes both in the acute and maintenance phases of bipolar disorder. Methods:, Definitions of response, remission, relapse, recovery, and recurrence are reviewed and recommendations for change are made. These suggestions include reporting the numbers needed to treat or harm (NNT or NNH), and a ratio of the two, likelihood of help or harm (LHH), as an important element of the effect size (ES). Moreover, models of prediction that conduct sensitivity or specificity analyses and utilize decision trees to help predict positive and negative outcomes of interest (for instance, excessive weight gain, or time to remission) using positive or negative predictive values (PPV or NPV) are reviewed for potential value to clinicians. Finally, functional and cognitive assessments are recommended for maintenance studies of bipolar disorder. Results:, The examples provided in this manuscript underscore that reporting the NNT or NNH, or alternative effect sizes, or using PPV or NPV may be of particular value to clinicians. Such reports are likely to help translate efficacy-driven clinical data to information that will more readily guide clinicians on the benefits and risks of specific interventions in bipolar disorder. Conclusions:, The authors opine that reporting these newer outcomes, such as NNT or NNH, area under the receiver operating curve (AUC), or PPV or NPV will help translate the results of clinical trials into a language that is more readily understood by clinicians. Moreover, assessing and evaluating functional and cognitive outcomes will not only inform clinicians about potential differences among therapeutic options, but likely will make it easier to communicate such differences to persons with bipolar illness or to their families. Finally, we hope such scientific and research efforts will translate to optimism for recovery-based outcomes in persons with bipolar disorder. [source] Paclitaxel and cisplatin as intravesical agents against non-muscle-invasive bladder cancerBJU INTERNATIONAL, Issue 11 2008Boris A. Hadaschik OBJECTIVES To investigate the effects of cisplatin and paclitaxel against human bladder cancer cells in vitro, and to obtain both pharmacokinetic and pharmacodynamic data after intravesical administration in mice. MATERIALS AND METHODS Six bladder cancer cell lines (J82, KU7, RT4, SW780, T24, UMUC3) were treated with various combined doses of both drugs and cell proliferation was evaluated 3 days later. In vivo, solutions of cisplatin and micellar paclitaxel were instilled transurethrally in female mice and pharmacokinetic data were acquired using high-performance liquid chromatography-mass spectrometry and atomic absorption methods. To obtain efficacy data, mice with orthotopic KU7-luc tumours were administered cisplatin and/or micellar paclitaxel intravesically, and the tumour burden quantified using bioluminescence imaging. RESULTS In vitro, both cisplatin and paclitaxel potently decreased the proliferation of all cell lines tested, and in combination had an additive but not a synergistic effect. After intravesical instillation, mouse serum concentrations of cisplatin and paclitaxel were in the low microgram/millilitre range and bladder tissue concentrations achieved were 82 and 241 µg/g, respectively. Similar drug levels were reached using combined therapy. In vivo, all chemotherapeutic agents significantly inhibited bladder tumour growth, with the best results for combined therapy and micellar paclitaxel alone. However, there was toxicity in the combined treatment arm. CONCLUSIONS Both cisplatin and paclitaxel were absorbed at effective amounts into bladder tissues. As intravesical agents, paclitaxel had slightly stronger anticancer potency than cisplatin. Due to increased adverse events, caution should be exercised when combining both cisplatin and paclitaxel intravesically. [source] Etanercept combined with methotrexate for high-need psoriasisBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2008R.J.B. Driessen Summary Background, For some high-need psoriatic patients, the efficacy of etanercept monotherapy is insufficient. In these cases it might be indicated to combine etanercept with other conventional treatments. Objectives, To provide daily practice safety and efficacy data for etanercept and methotrexate combination therapy. Methods, Data were extracted from an existing database, which contains prospective safety and efficacy data of all patients who were treated with etanercept in clinical practice. A case was defined as a patient using etanercept and methotrexate simultaneously for an indefinite period during follow-up. For all cases, baseline data, Psoriasis Area and Severity Index (PASI) scores, adverse events and laboratory values were investigated. Furthermore, the influence of introduction and discontinuation of methotrexate on these parameters was analysed. Results, Fourteen patients with simultaneous use of etanercept and methotrexate were selected. In six patients, methotrexate was introduced after etanercept to avoid further psoriasis deterioration, which resulted in an improvement of psoriasis in four of these patients. Eight patients were on methotrexate therapy before start of etanercept. Discontinuation of methotrexate in six of these patients resulted in a decrease in PASI improvement in five patients. Etanercept combined with methotrexate was well tolerated, and only mild adverse events were reported. No clinically significant changes in laboratory parameters occurred. Conclusions, Results show that combining etanercept with methotrexate is reasonable when efficacy of etanercept monotherapy is insufficient, or when rapid deterioration of psoriasis after abrupt discontinuation of methotrexate is expected. Laboratory values and adverse events were not different from what would have been expected when using methotrexate alone. [source] Treating cancer with PEG IntronCANCER, Issue 2 2002Pharmacokinetic profile, dosing guidelines for an improved interferon-alpha-2b formulation Abstract BACKGROUND PEG Intron (pegylated interferon-alpha-2b [IFN-,-2b]; Schering-Plough, Kenilworth, NJ) has demonstrated delayed clearance and increased area under the curve compared with native IFN-,-2b. Studies in patients with chronic hepatitis C infection and malignancies have demonstrated both biologic and clinical activity of PEG Intron and have provided empiric data to compare the pharmacokinetics (PK) and pharmacodynamics of PEG Intron and IFN-,-2b. METHODS The authors conducted a review of the available data comparing the PK and pharmacodynamic effects of PEG Intron and IFN-,-2b. Safety and efficacy data from Phase I/II studies of PEG Intron in patients with chronic myelogenous leukemia (CML) and solid tumors were also reviewed. RESULTS Data from patients with chronic hepatitis C infection suggest that exposure to IFN at a PEG Intron dose of 0.25 ,g/kg per week is similar to that observed after administration of IFN-,-2b at a dose of 3 million International Units, three times per week. PEG Intron at doses up to 6 ,g/kg per week was well tolerated and demonstrated clinical activity in patients with CML and solid tumors, including metastatic melanoma and renal cell carcinoma. CONCLUSIONS Dose intensification can be achieved safely in patients with CML and solid tumors using PEG Intron, which could improve efficacy. These results provide useful dosing guidelines to clinicians investigating the antitumor activity of PEG Intron in patients with malignancies. More data are needed to determine the optimal dose in various oncologic indications. However, these results provide a sound rationale for further investigation of PEG Intron. Cancer 2002;95:389,96. © 2002 American Cancer Society. DOI 10.1002/cncr.10663 [source] Domperidone versus cisapride in the treatment of infant regurgitation and increased acid gastro-oesophageal reflux: a pilot studyACTA PAEDIATRICA, Issue 4 2009Badriul Hegar Abstract Aim: Although domperidone is used frequently to treat infant regurgitation, efficacy data are scarce. Cisapride was previously used in the same indication. Methods: Domperidone and cisapride were compared in an investigator-blinded, prospective comparative trial by evaluating (a) the frequency of regurgitation, (b) acid reflux and (c) cardiac side effects in infants regurgitating >4 times/day since >2 weeks and with reflux-associated symptoms of discomfort, after conservative treatment failure. Results: Within the first treatment week, the frequency of regurgitation decreased in both groups, more rapidly in the cisapride group: the median regurgitation decreased from 6.22 to 3.50 in the cisapride group versus from 4.80 to 3.70 in the domperidone group. The decrease in regurgitation was still significant after 1 month: cisapride from 6.22 to 1.55 versus domperidone from 4.80 to 1.25. However, the natural decrease in the incidence of regurgitation induced by age should also be considered. The median reflux index decreased after 1 month in the cisapride group from 3.60 to 1.75 versus from 2.70 to 2.45 in the domperidone group. One child treated with cisapride developed a significant QT prolongation. Conclusion: The decrease in regurgitation was comparable in both groups, although acid reflux decreased more in the cisapride group. Cisapride induced QT prolongation in one infant. [source] Antidepressants in clinical practice: limitations of assessment methods and drug responseHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 1 2001Sidney H Kennedy Abstract There is a recognized gap between knowledge derived from ,efficacy' data , based on usually brief randomized controlled trials and findings in natural practice ,effectiveness' studies. In considering the limitations of current antidepressants in clinical practice, we have selected three clinically important issues to examine in a natural practice data base that has been in existence for several years. These relate to: (1) Diagnostic heterogeneity and potential advances using functional brain imaging; (2) Variability of outcome measures during treatment and (3) Time to response and prediction of outcome. Copyright © 2001 John Wiley & Sons, Ltd. [source] | ||||||||||||||||||||||||||||