Efficacy gap between phase II and subsequent phase III studies in oncology.


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.


Br J Clin Pharmacol


Vreman RA,Belitser SV,Mota ATM,Hövels AM,Goettsch WG,Roes KCB,Leufkens HGM,Mantel-Teeuwisse AK




Has Abstract


2020-07-01 00:00:00












  • The psychopharmacological and electrophysiological effects of single doses of caffeine in healthy human subjects.

    abstract::The effects of single doses of anhydrous caffeine (250 mg and 500 mg) and placebo on physiological, psychological measures and subjective feelings were studied in a double-blind, cross-over study in nine healthy subjects who had abstained from caffeine-containing beverages for 24 h before each occasion. Caffeine and c...

    journal_title:British journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Bruce M,Scott N,Lader M,Marks V

    更新日期:1986-07-01 00:00:00

  • Beta 2-adrenoceptor up-regulation in relation to cAMP production in human lymphocytes after physical exercise.

    abstract::The effect of isotonic bicycle exercise on beta 2-adrenoceptors and cAMP production in lymphocytes was studied. The origin of the newly exposed receptors was studied by measuring radioligand binding in the presence of hydrophylic or lipophylic 'cold' ligands. During exercise beta 2-adrenoceptor density increased from ...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Graafsma SJ,van Tits LJ,Willems PH,Hectors MP,Rodrigues de Miranda JF,De Pont JJ,Thien T

    更新日期:1990-01-01 00:00:00

  • Improved physical performance as a therapeutic objective in patients with angina.

    abstract::1 Improvement in physical performance, based on exercise tolerance, self-assessed work and physician-rated functional capacities, is proposed as a measure of efficacy of anti-anginal therapy in the rehabilitation of the cardiac patient. 2 Improved physical performance parallels changes in frequency of anginal attacks ...

    journal_title:British journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Ling AS,Groel JT

    更新日期:1979-01-01 00:00:00

  • Effects of Schisandra sphenanthera extract on the pharmacokinetics of tacrolimus in healthy volunteers.

    abstract:AIM:To assess the effect of Schisandra sphenanthera extract (SchE) on the pharmacokinetics of tacrolimus in healthy volunteers. METHODS:Twelve healthy male volunteers were orally treated with SchE, three capsules twice daily for 13 days. Pharmacokinetic investigations of oral tacrolimus administration at 2 mg were per...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Xin HW,Wu XC,Li Q,Yu AR,Zhu M,Shen Y,Su D,Xiong L

    更新日期:2007-10-01 00:00:00

  • Intestinal absorption of strontium chloride in healthy volunteers: pharmacokinetics and reproducibility.

    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


    authors: Sips AJ,van der Vijgh WJ,Barto R,Netelenbos JC

    更新日期:1996-06-01 00:00:00

  • CYP2D6 polymorphism in a Gabonese population: contribution of the CYP2D6*2 and CYP2D6*17 alleles to the high prevalence of the intermediate metabolic phenotype.

    abstract:AIMS:To determine the molecular basis of the intermediate extensive metaboliser (EM) CYP2D6 phenotype in healthy Gabonese subjects. METHODS:The CYP2D6 phenotype of 154 healthy Gabonese subjects was assessed by giving the subject a single dose of 30 mg dextromethorphan, and collecting their urine for the next 8 h. The ...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Panserat S,Sica L,Gérard N,Mathieu H,Jacqz-Aigrain E,Krishnamoorthy R

    更新日期:1999-01-01 00:00:00

  • Systemic exposure to 5-fluorouracil and its metabolite, 5,6-dihydrofluorouracil, and development of a limited sampling strategy for therapeutic drug management of 5-fluorouracil in patients with gastrointestinal malignancy.

    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


    authors: Jacob J,Mathew SK,Chacko RT,Aruldhas BW,Singh A,Prabha R,Mathew BS

    更新日期:2020-06-27 00:00:00

  • Possible association between ocular chloramphenicol and aplastic anaemia--the absolute risk is very low.

    abstract:AIMS:To determine whether topical ocular chloramphenicol increases the risk of aplastic anaemia and to estimate the magnitude of this risk, if any. METHODS:Population-based prospective case-control surveillance of aplastic anaemia in a community of 4.2 million inhabitants from 1980 to 1995 (67.2 million person-years) ...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Laporte JR,Vidal X,Ballarín E,Ibáñez L

    更新日期:1998-08-01 00:00:00

  • Selective beta-adrenoceptor partial agonist effects of pindolol and xamoterol on skeletal muscle assessed by plasma creatine kinase changes in healthy subjects.

    abstract::1. The effects of selective beta-adrenoceptor partial agonist activity on plasma creatine kinase (CK) and skeletal muscle symptoms were studied in normal volunteers. 2. A drug with beta 1-selective partial agonist activity (xamoterol) and one with partial agonist activity acting mainly through beta 2-adrenoceptors (pi...

    journal_title:British journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Tomlinson B,Cruickshank JM,Hayes Y,Renondin JC,Lui JB,Graham BR,Jones A,Lewis AD,Prichard BN

    更新日期:1990-11-01 00:00:00

  • Detection of autoantibodies directed against human hepatic endoplasmic reticulum in sera from patients with halothane-associated hepatitis.

    abstract::1. Previous studies have demonstrated the presence of antibodies to trifluoroacetylated hepatic proteins (TFA-proteins) in sera from patients with the severe form of halothane-associated hepatitis (halothane hepatitis). The TFA-proteins are produced via cytochrome P450-mediated metabolism of halothane to the reactive ...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Kitteringham NR,Kenna JG,Park BK

    更新日期:1995-10-01 00:00:00

  • Toxicity of nitrazepam in the elderly: a report from the Boston Collaborative Drug Surveillance Program.

    abstract::1 To assess the potential hazards of nitrazepam therapy of insomnia in the elderly, adverse reactions to nitrazepam were studied in 2111 hospitalized medical patients who received the drug. 2 Manifestations of unwanted central nervous system (CNS) depression (such as drowsiness or 'hangover') were reported in 49 nitra...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Greenblatt DJ,Allen MD

    更新日期:1978-05-01 00:00:00

  • Impact of CYP2D6 on serum concentrations of flupentixol, haloperidol, perphenazine and zuclopenthixol.

    abstract:AIMS:To investigate the impact of cytochrome P450 2D6 (CYP2D6) on dose-adjusted serum concentrations of flupentixol, haloperidol, perphenazine and zuclopenthixol in a therapeutic drug monitoring (TDM) cohort of psychiatric patients. We also studied the functional impact of CYP2D6*41 on dose-adjusted serum concentration...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Waade RB,Solhaug V,Høiseth G

    更新日期:2020-10-28 00:00:00

  • Nonmedical use of alprazolam in the UK: Results from a nationally representative survey.

    abstract::There is concern in the UK about nonmedical use (NMU) of alprazolam (Xanax). We investigated the epidemiology of alprazolam NMU compared with diazepam using data from the Survey of Non-Medical Use of Prescription Drugs (NMURx) programme (collected 28 September-1 December 2017). The survey included 10 019 respondents a...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Hockenhull J,Amioka E,Black JC,Haynes CM,Dargan PI,Dart RC,Wood DM

    更新日期:2019-08-01 00:00:00

  • Does it matter where we measure blood pressure?

    abstract::Although blood pressure measured at the brachial artery plays a central role in our understanding and management of cardiovascular risk, in recent years great emphasis has been placed on the importance of central blood pressure. It seems straightforward that knowledge of the blood pressure directly affecting the major...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章,评审


    authors: Tomlinson LA,Wilkinson IB

    更新日期:2012-08-01 00:00:00

  • Growth factors for diabetic foot ulcers: mixed treatment comparison analysis of randomized clinical trials.

    abstract:AIMS:Topical growth factors accelerate wound healing in patients with diabetic foot ulcers (DFU). Due to the absence of head-to-head comparisons, we carried out Bayesian network meta-analysis to compare the efficacy and safety of growth factors. METHODS:Using an appropriate search strategy, randomized controlled trial...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章,meta分析


    authors: Sridharan K,Sivaramakrishnan G

    更新日期:2018-03-01 00:00:00

  • Impaired β-adrenoceptor mediated venodilation in patients with diabetes mellitus.

    abstract::Aims We investigated whether venoconstriction by α-adrenoceptor stimulation, and venodilation by β-adrenoceptor stimulation and nitroglycerin are altered in patients with diabetes mellitus (DM). Methods Eight male patients with non insulin-dependent DM and eight age-matched control subjects were included. The patients...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Harada K,Ohmori M,Kitoh Y,Sugimoto KI,Fujimura A

    更新日期:1999-04-01 00:00:00

  • Effects of fluticasone vs. fluticasone/salmeterol on airway calibre and airway hyperresponsiveness in mild persistent asthma.

    abstract:AIMS:Inhaled corticosteroids alone or in combination with long acting beta2-agonists are indicated for use in mild persistent asthmatics. We set out to evaluate effects on airway hyperresponsiveness (AHR) and airway calibre using hydrofluoroalkane fluticasone/salmeterol (FP/SM) vs. double the dose of fluticasone alone ...

    journal_title:British journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Currie GP,Stenback S,Lipworth BJ

    更新日期:2003-07-01 00:00:00

  • Calcium antagonists stimulate sperm motility in ejaculated human semen.

    abstract::Three calcium antagonists, diltiazem, flunarizine and verapamil stimulated human sperm motility in vitro. Among them, diltiazem induced the largest amplitude of motility increase. The concentration-response curve of diltiazem was similar in shape to those of calcium chelators. EGTA, a calcium chelator, potentiated the...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Hong CY,Chiang BN,Ku J,Wei YH,Fong JC

    更新日期:1985-01-01 00:00:00

  • Bioactivation of dapsone to a cytotoxic metabolite: in vitro use of a novel two compartment system which contains human tissues.

    abstract::1. A two compartment system, comprising two adjacent teflon chambers separated by a semi-permeable membrane, has been devised with which to investigate the generation of drug metabolites that are toxic to human cells in vitro. 2. Compartment A contained a drug-metabolising system (human liver microsomes +/- NADPH) and...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Riley RJ,Roberts P,Coleman MD,Kitteringham NR,Park BK

    更新日期:1990-09-01 00:00:00

  • What benefit do patients expect from adding second and third antihypertensive drugs?

    abstract:AIMS:To discover whether patients have the same expectations of benefit from taking the first and any additional drugs for the treatment of hypertension and to investigate any patient characteristics which predict willingness to take treatment. METHODS:This was an anonymous questionnaire survey carried out in a single...

    journal_title:British journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Leaman H,Jackson PR

    更新日期:2002-01-01 00:00:00

  • Risk factors contributing to a low darunavir plasma concentration.

    abstract::Darunavir is an efficacious drug; however, pharmacokinetic variability has been reported. The objective of this study was to find predisposing factors for low darunavir plasma concentrations in patients starting the once- or twice-daily dosage. Darunavir plasma concentrations from January 2010 till December 2014 of hu...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Daskapan A,Stienstra Y,Kosterink JGW,Bierman WFW,van der Werf TS,Touw DJ,Alffenaar JC

    更新日期:2018-03-01 00:00:00

  • Flavonoids inhibit the platelet TxA(2) signalling pathway and antagonize TxA(2) receptors (TP) in platelets and smooth muscle cells.

    abstract:AIMS:Flavonoids may affect platelet function by several mechanisms, including antagonism of TxA(2) receptors (TP). These TP are present in many tissues and modulate different signalling cascades. We explored whether flavonoids affect platelet TP signalling, and if they bind to TP expressed in other cell types. METHODS...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Guerrero JA,Navarro-Nuñez L,Lozano ML,Martínez C,Vicente V,Gibbins JM,Rivera J

    更新日期:2007-08-01 00:00:00

  • Clinical pharmacology and therapeutics in undergraduate medical education in the UK: the future.

    abstract::1. Changes in undergraduate medical education will involve the development of a core curriculum of material of essential knowledge and of the skills for self directed learning both as a student and a postgraduate. A survey of departments or individuals teaching clinical pharmacology and therapeutics was conducted to c...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Walley T,Bligh J,Orme M,Breckenridge A

    更新日期:1994-02-01 00:00:00

  • Favourable dermal penetration of diclofenac after administration to the skin using a novel spray gel formulation.

    abstract:AIMS:The study was designed to evaluate the relative bioavailability of diclofenac in plasma, subcutaneous adipose and skeletal muscle tissue after repeated topical administration using MIKA Diclofenac Spray Gel (4%), a novel formulation, and after oral dosing using VOLTAREN 50 mg enteric coated tablets. METHODS:Diclo...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Brunner M,Dehghanyar P,Seigfried B,Martin W,Menke G,Müller M

    更新日期:2005-11-01 00:00:00

  • Influence of various antihypertensive agents on lifespan of renal hypertensive rats.

    abstract::1 Daily treatment of two-kidney clipped renal hypertensive rats with hydrallazine, hydrochlorothiazide (HCTZ) and a new orally active inhibitor of the angiotensin-converting enzyme, captopril (SQ14,225), was correlated with survival rates for up to 9 months. 2 The groups of rats given captopril alone or captopril plus...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Horovitz ZP,Antonaccio MJ,Rubin B,Panasevich RE

    更新日期:1979-01-01 00:00:00

  • Quality and safety of herbal medical products: regulation and the need for quality assurance along the value chains.

    abstract::Herbal medicines and products derived from them are a diverse group of products for which different (and often limited) levels of evidence are available. As importantly, such products generally vary in their composition and are at the end of an often poorly understood value chain, which often links producers in biodiv...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章,评审


    authors: Heinrich M

    更新日期:2015-07-01 00:00:00

  • Undertreatment of hypertension and hypercholesterolaemia in children and adolescents with type 1 diabetes: long-term follow-up on time trends in the occurrence of cardiovascular disease, risk factors and medications use.

    abstract:AIMS:The aims of the present study were, firstly, to evaluate long-term trends in the occurrence and treatment of cardiovascular disease (CVD) risk factors and the occurrence of CVD events in children with type 1 diabetes mellitus (T1DM) and, secondly, to assess the determinants of undertreatment of CVD risk factors. ...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Ahmadizar F,Souverein P,de Boer A,Maitland-van der Zee AH

    更新日期:2018-04-01 00:00:00

  • Plasma protein-binding and CSF concentrations of valproic acid in man following acute oral dosing.

    abstract::Simultaneous cerebrospinal fluid (CSF), total and free plasma valproic acid (VPA) concentrations were measured in 17 patients receiving two weight-adjusted VPA doses as seizure prophylaxis prior to diagnostic myelography or cisternography. Free drug concentrations were similar when measured by equilibrium dialysis (ED...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Rapeport WG,Mendelow AD,French G,MacPherson P,Teasdale E,Agnew E,Thompson GG,Brodie MJ

    更新日期:1983-10-01 00:00:00

  • The measurement of haloperidol and reduced haloperidol in hair as an index of dosage history.

    abstract::1. We report a method for measuring the concentrations of haloperidol (HL) and its major active metabolite, reduced haloperidol (RHL), in human scalp hair. 2. Hair samples were obtained from 59 patients who had been taking HL at fixed daily doses for more than 4 months and whose compliance was good. A morning pre-dose...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Matsuno H,Uematsu T,Nakashima M

    更新日期:1990-02-01 00:00:00

  • Intravenous midazolam for upper gastrointestinal endoscopy: a study of 800 consecutive cases relating dose to age and sex of patient.

    abstract::In many endoscopy units midazolam is replacing diazepam as the intravenous sedative of first choice. Midazolam is approximately twice as potent as diazepam. Although generally considered a safe drug, there have been a number of recent reports, particularly in the elderly, of the drug causing hypotension, respiratory d...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Bell GD,Spickett GP,Reeve PA,Morden A,Logan RF

    更新日期:1987-02-01 00:00:00