Abstract：
AIMS:There is a trend for more flexibility in timing of evidence generation in relation to marketing authorization, including the option to complete phase III trials after authorization or not at all. This paper investigated the relation between phase II and III clinical trial efficacy in oncology. METHODS:All oncology drugs approved by the European Medicines Agency (2007-2016) were included. Phase II and phase III trials were matched based on indication and treatment and patient characteristics. Reported objective response rates (ORR), median progression-free survival (PFS) and median overall survival (OS) were analysed through weighted mixed-effects regression with previous treatment, treatment regimen, blinding, randomization, marketing authorization type and cancer type as covariates. RESULTS:A total of 81 phase II-III matches were identified including 252 trials. Mean (standard deviation) weighted difference (phase III minus II) was -4.2% (17.4) for ORR, 2.1 (6.7) months for PFS and -0.3 (5.1) months for OS, indicating very small average differences between phases. Differences varied substantially between individual indications: from -46.6% to 47.3% for ORR, from -5.3 to 35.9 months for PFS and from -13.3 to 10.8 months for OS. All covariates except blinding were associated with differences in effect sizes for at least 1 outcome. CONCLUSIONS:The lack of marked average differences between phases may encourage decision-makers to regard the quality of design and total body of evidence instead of differentiating between phases of clinical development. The large variability emphasizes that replication of study findings remains essential to confirm efficacy of oncology drugs and discern variables associated with demonstrated effects.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Vreman RA,Belitser SV,Mota ATM,Hövels AM,Goettsch WG,Roes KCB,Leufkens HGM,Mantel-Teeuwisse AKdoi
10.1111/bcp.14237subject
Has Abstractpub_date
2020-07-01 00:00:00pages
1306-1313issue
7eissn
0306-5251issn
1365-2125journal_volume
86pub_type
杂志文章abstract：AIMS:To assess the age-associated changes over time of plasma paraxanthine/caffeine (PAX/CAF) ratios used as a probe for CYP1A2 activity. METHODS:Intraindividual and interindividual variabilities in PAX/CAF ratio were compared by phenotyping with caffeine, 16 young and 16 elderly healthy subjects on five occasions. R...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.0306-5251.2001.01494.x
更新日期：2001-11-01 00:00:00
abstract：:1. In order to investigate accurately the biochemical effects of renin inhibition in man, we have developed a sensitive assay to measure angiotensin I (1-10) decapeptide. 2. Angiotensins were extracted from plasma by adsorption to phenylsilylsilica, and angiotensin I (Ang I) was quantified by radioimmunoassay. The det...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1992.tb04032.x
更新日期：1992-03-01 00:00:00
abstract：AIMS:Aldosterone has been found to influence cancer cell growth, cell cycle regulation and cell migration, including in prostate cancer cells. Spironolactone is an aldosterone antagonist used for managing chronic heart failure (HF) with known antiandrogenic effects. We examined the effect of spironolactone exposure amo...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.14568
更新日期：2020-09-28 00:00:00
abstract：AIMS:Previous pharmacokinetic characterization of a transporter probe cocktail containing digoxin (P-gp), furosemide (OAT1, OAT3), metformin (OCT2, MATE1, MATE2-K) and rosuvastatin (OATP1B1, OATP1B3, BCRP) in healthy subjects showed increases in rosuvastatin systemic exposure compared to rosuvastatin alone. In this tri...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/bcp.13609
更新日期：2018-09-01 00:00:00
abstract：AIMS:It is estimated that two-thirds of cancer patients will at some point during their illness experience breakthrough pain. In this study, the pharmacokinetics of a novel sublingual dosage form of fentanyl developed for breakthrough pain was evaluated. METHODS:Eleven Caucasian patients (seven male and 4 female, aged...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.2004.02264.x
更新日期：2005-02-01 00:00:00
abstract：:1. The absorption kinetics of orally administered strontium chloride and its reproducibility were investigated in healthy volunteers after administering strontium either under fasting conditions (study I, n = 8) or in combination with a standardized meal (study II, n = 8). Each subject received strontium orally at day...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1046/j.1365-2125.1996.33411.x
更新日期：1996-06-01 00:00:00
abstract：:1. Determination of debrisoquine oxidation phenotype was carried out in 119 healthy subjects, 135 patients with chronic bronchitis and 153 patients with lung cancer, all of Caucasian origin. 2. A non-Gaussian distribution of the log D/HD ratio was observed in the three groups. 3. Assuming an antimode of 1.12, the prop...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1991.tb05575.x
更新日期：1991-05-01 00:00:00
abstract：:1. Relative rates of absorption of enteric and non-enteric preparations of prednisolone were measured in five renal transplant recipients. 2. The absorption of the enteric coated preparation is delayed and the peak plasma concentration is much lower than that attained using the same dose of the uncoated material. 3. T...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1975.tb02777.x
更新日期：1975-08-01 00:00:00
abstract：:The present study was designed to evaluate the potential anti-ischaemic activity of R 56865 in patients with coronary artery disease, scheduled to undergo percutaneous transluminal coronary angioplasty (PTCA). At baseline a complete haemodynamic profile, including cardiac output and coronary sinus blood flow (CSBF) wa...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1995.tb04491.x
更新日期：1995-05-01 00:00:00
abstract：:The antiarrhythmic effects of verapamil were observed before it was appreciated that it was a calcium ion-antagonist. Intravenous verapamil is highly effective in the termination of paroxysmal reciprocating atrioventricular tachycardia, whether associated with preexcitation or involving the atrioventricular node alone...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1365-2125.1986.tb02869.x
更新日期：1986-01-01 00:00:00
abstract：:The psychomotor and cardiovascular effects of minaprine 100 mg, a novel antidepressant, were compared with amitriptyline 25 mg, as a positive control, and placebo in a single dose randomised double-blind crossover trial using an automated psychomotor test battery (APT), postural sway (PS), blood pressure (BP) and puls...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1993.tb00381.x
更新日期：1993-10-01 00:00:00
abstract：:The degrees of interactions between the H2-receptor antagonists, cimetidine and ranitidine, and several beta-adrenoceptor blockers were investigated in healthy volunteers following 7 days of oral monotherapy with penbutolol, propranolol, metoprolol, pindolol and atenolol, and after co-administration with each of the H...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1984.tb02428.x
更新日期：1984-01-01 00:00:00
abstract：:1. The dose-related effects of azapropazone on (i) event-related and spontaneous EEG-activity and (ii) the subjects' pain ratings were investigated using an experimental human pain model based on both chemo-somatosensory event-related potentials (CSSERP) and subjects' pain ratings. 2. Healthy subjects (n = 20) partici...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1995.tb05799.x
更新日期：1995-12-01 00:00:00
abstract：AIMS:Navoximod (GDC-0919, NLG-919) is a small molecule inhibitor of indoleamine-2,3-dioxygenase 1 (IDO1), developed to treat the acquired immune tolerance associated with cancer. The primary objectives of this study were to assess navoximod's absolute bioavailability (aBA), determine the mass balance and routes of elim...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.13961
更新日期：2019-08-01 00:00:00
abstract：:1. The influence of food on the absorption of frusemide and bumetanide was compared in two separate randomized crossover studies. 2. On three separate occasions frusemide 40 mg was administered to eight healthy male volunteers intravenously, orally in the fasting state and orally after a standard breakfast. Blood and ...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1046/j.1365-2125.1996.00494.x
更新日期：1996-12-01 00:00:00
abstract：AIMS:The aim of this study was to use data from an experimental induced blood stage malaria clinical trial to characterize the antimalarial activity of the new compound Actelion-451840 using pharmacokinetic/pharmacodynamic (PK/PD) modelling. Then, using simulations from the model, the dose and dosing regimen necessary ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.12962
更新日期：2016-08-01 00:00:00
abstract：:1 The pharmacodynamic profile of single oral doses of prorenoate potassium (40 mg) and spironolactone (100 mg), as judged by reversal of the effects of fludrocostisone on the urinary electrolyte composition, was compared to that of placebo in a double-blind crossover study in six healthy subjects. 2 Both drugs showed ...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1976.tb00624.x
更新日期：1976-06-01 00:00:00
abstract：:1 The relationship between serum quinidine levels and rate-corrected QT (QTc) interval after administration of single identical doses of quinidine was assessed. Quinidine concentrations were determined by a modification of Hamfelt & Malers' (1963) method. The significance and clinical application of our findings is di...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1974.tb01694.x
更新日期：1974-12-01 00:00:00
abstract：AIMS:Pupillography is a noninvasive and cost-effective method to determine autonomic nerve activity. Genetic variants in cytochrome P450 (CYP), dopamine receptor (DRD2, DRD3), serotonin receptor (HTR2A, HTR2C) and ATP-binding cassette subfamily B (ABCB1) genes, among others, were previously associated with the pharmaco...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.14300
更新日期：2020-10-01 00:00:00
abstract：:1. To assess the risk of end-stage renal disease (ESRD) associated with the regular use of three classes of non-narcotic analgesics, we performed a case-control study of 340 patients with ESRD on a haemodialysis maintenance program and 673 hospital controls. 2. The overall odds ratio estimate for non-narcotic analgesi...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1990.tb03841.x
更新日期：1990-11-01 00:00:00
abstract：AIMS:To determine whether and to what extent bronchoconstriction affects plasma concentrations of fluticasone and budesonide following inhalation. METHODS:Twenty people with mild asthma inhaled 1000 microg fluticasone (Accuhaler) plus 800 microg budesonide (Turbohaler) on two visits. On one occasion, prior to drug inh...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/j.1365-2125.2007.02856.x
更新日期：2007-10-01 00:00:00
abstract：:Children are not small adults. However, the main thesis of this review will be that children's responses to drugs have much in common with the responses in adults and indeed in other mammals. Often, it is assumed that drug effects differ in children but in reality this perception often arises because the drugs have no...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1365-2125.2005.02445.x
更新日期：2005-06-01 00:00:00
abstract：AIMS:To investigate the effect of multiple oral dose treatment with the endothelin receptor antagonist bosentan on the pharmacokinetics of digoxin in healthy subjects. METHODS:This was an open-label, randomized, two-way crossover study in 18 evaluable young male subjects. They received, on two occasions which were sep...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1046/j.1365-2125.1999.00946.x
更新日期：1999-06-01 00:00:00
abstract：AIMS:This study aimed to analyse the effects of genetic polymorphisms in drug transporters and metabolizing enzymes, and clinical laboratory data on the pharmacokinetic parameters of apixaban. METHODS:Data were collected from 81 Japanese patients with atrial fibrillation. Pharmacogenomic data were stratified by ABCB1,...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.13561
更新日期：2018-06-01 00:00:00
abstract：:Individual and population differences in polymorphic cytochrome P450 enzyme function have been known for decades. The biological significance of these differences has now been deciphered with regard to drug metabolism, action and toxicity as well as disposition of endogenous substrates, including neuroactive compounds...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bcp.12227
更新日期：2014-04-01 00:00:00
abstract：AIMS:5-Fluorouracil (5-FU) is widely used in combination chemotherapy, and literature suggests pharmacokinetic-guided dosing to improve clinical efficacy and reduce toxicity. This study aimed to determine the pharmacokinetic exposure of both 5-FU and its metabolite, 5,6-dihydrofluorouracil (DHFU), in patients with gast...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.14444
更新日期：2020-06-27 00:00:00
abstract：:1 Analgesic nephropathy is part of the analgesic syndrome which has gastrointestinal, haematological, cardiovascular, psychological and psychiatric, and pregnancy and gonadal manifestations; premature ageing may also be a feature. 2 Analgesic nephropathy is a form of renal disease characterized by renal papillary necr...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1365-2125.1980.tb01824.x
更新日期：1980-10-01 00:00:00
abstract：:1. We have studied the effects of age, sex and the oral contraceptive pill on platelet fibrinogen 'receptor' density (Bmax) and affinity (Kd). 2. [125I]-fibrinogen binding to gel-filtered platelets was assessed after stimulation with adenosine 5-diphosphate (ADP) and thrombin in 60 normal subjects; 37 females and 23 m...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1992.tb03994.x
更新日期：1992-01-01 00:00:00
abstract：AIM:Pharmacokinetics of small molecule kinase inhibitors (KIs) used in cancer treatment may alter with increasing age, but results are conflicting. This study aims to compare exposure to KIs between older and younger patients (≥70 and <70 years) in clinical practice. METHODS:KI plasma concentrations of routinely treat...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.13725
更新日期：2018-12-01 00:00:00
abstract：:Rituximab is a B-cell depleting monoclonal antibody that is gaining popularity as an effective therapy for many autoimmune cytopenias. This article systematically evaluates its therapeutic efficacy in the treatment of different types of autoimmune haemolytic anaemia. We conclude that there is sufficient evidence to re...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bcp.12498
更新日期：2015-05-01 00:00:00
