Clinical Drug Investigation (CLIN DRUG INVEST)
Clinical Drug Investigation gives you rapid access to the best designed, peer reviewed clinical and pharmacoeconomic studies worldwide, allowing you to keep up to date with the latest original research in this exciting area. The Journal's aim is rapid publication of original research covering all phases of clinical drug development and therapeutic use of drugs. This includes clinical trials, outcomes research, clinical pharmacoeconomic studies, pharmacoepidemiology studies with a strong link to optimum prescribing practice for a drug or group of drugs, clinical pharmacodynamic and clinical pharmacokinetic studies with a strong link to clinical practice and, in some instances, pharmacodynamic or pharmacokinetic studies in healthy volunteers, but in which some established or purported implications for clinical prescribing are discussed. In addition, short communications and case study reports that meet these criteria are also encouraged, as are letters to the editor.
Journal Impact: 2.44*
Journal impact history
|2016 Journal impact||Available summer 2017|
|2015 Journal impact||2.44|
|2014 Journal impact||2.69|
|2013 Journal impact||2.21|
|2012 Journal impact||2.10|
Journal impact over time
|Website||Clinical Drug Investigation website|
|Material type||Periodical, Internet resource|
|Document type||Journal / Magazine / Newspaper, Internet Resource|
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Publications in this journal
- [Show abstract] [Hide abstract] ABSTRACT: Background and objective: The cost-effectiveness of highly effective, but costly, peg-interferon (peg-IFN) treatment for chronic hepatitis B (CHB) infections in China is unknown. Endemic hepatitis D virus (HDV) may also modify the effectiveness of any HBV treatment option. The objective of this study is to determine the best antiviral treatment from a societal perspective in the Chinese population, which contains a mix of HBV and HDV infections. Methods: A Markov model is developed to simulate the clinical course of CHB and chronic hepatitis D (CHD) individuals. For a hypothetical Chinese cohort of 10,000 individuals aged 30-60 years, cost-utility analysis is performed for therapies with: lamivudine, adefovir, telbivudine, entecavir, IFN and Peg-IFN. Costs and quality-adjusted life-years (QALYs) are discounted at 3 % annually. A one-way sensitivity analysis is also conducted. Results: Lamivudine, adefovir, telbivudine, and entecavir are all cost-effective treatments compared to palliative care at an incremental cost-effectiveness ratio (ICER) of -$418, -$197, -$443 and -$317 per QALY, respectively (2015 US dollars). Peg-IFN yields a maximum 156,000 QALYs with an ICER of $1149 per QALY while IFN results in the highest cumulative mortality of 48 % along with the lowest QALY gained. Probabilistic sensitivity analyses confirm that only Peg-IFN and ETV are the only two cost-effective options at the current willingness-to-pay (WTP) of $12,000 in China. However, entecavir has a higher probability of being cost-effective than Peg-IFN at current WTP for all age groups. Conclusions: Peg-IFN generates maximum QALYs compared to lamivudine, adefovir, telbivudine and interferon, and presents itself as a cost-effective option at current WTP. Alternatively entecavir can be used in China, generating 10 % lower QALYs than Peg-IFN but costing less than palliative care.
- [Show abstract] [Hide abstract] ABSTRACT: Background and objective: Selecting the most effective treatment for major depressive disorder (MDD) is a challenge for clinicians. The aim of this study was to compare the effects of sertraline with duloxetine on major depression signs and symptoms. Methods: The trial was a 6-week, randomized, controlled, double-blind study. Sixty-three patients with diagnosis of MDD according to DSM-IV-TR criteria were randomly assigned to receive either duloxetine (31 patients) or sertraline (32 patients). The mean dosage of duloxetine was 55 mg/day (range 40-60 mg/day) and the mean dosage of sertraline was 146 mg/day (range 50-200 mg/day). Subjects were assessed at baseline, and at the end of week 6. Depression severity and symptoms were assessed by 21-item Hamilton Depression Rating Scale (HAM-D). Results: Of 63 patients who were randomized to treatment, 54 patients including 28 in the sertraline group and 26 in the duloxetine group completed the trial. The HAM-D total score for both groups was significantly reduced at the end of the trial period without significant difference from each other (p = 0.463). Of the symptoms studied, psychomotor retardation, general somatic symptoms and sexual problems improved more in the duloxetine group. On the other hand, agitation, anxiety symptoms and hypochondriasis ameliorated better in the sertraline group. There was no difference between the two groups regarding the other symptoms. Conclusions: Our study shows that the antidepressant mechanism of action has influence on its effects on different signs and symptoms. Clinician awareness of an antidepressant's special effects can help in selecting appropriate medicine.
- [Show abstract] [Hide abstract] ABSTRACT: Background and objective: Vortioxetine and duloxetine are two new antidepressant drugs that have been used clinically in the treatment of major depressive disorder (MDD). The objectives of this meta-analysis were to evaluate the efficacy and tolerability of vortioxetine compared with duloxetine in MDD. Methods: Randomized controlled trials (RCTs) published in PubMed, EMBASE, Web of Science, and ClinicalTrials.gov were systematically reviewed to compare vortioxetine with duloxetine in terms of efficacy and tolerability in patients with MDD. Results were expressed as the risk ratio (RR) with 95 % confidence intervals (CIs), and weighted mean difference (WMD). Pooled estimates were calculated by using a fixed-effects model or a randomized-effects model, depending on the heterogeneity among studies. Results: A total of five RCTs involving 2287 patients met the inclusion criteria and were included in this meta-analysis. Pooled results showed that duloxetine was associated with a higher response rate than vortioxetine, as well as showing a similar remission rate with vortioxetine. The changes from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS), 24-item Hamilton Rating Scale for Depression (HAM-D24), Clinical Global Impression-Improvement scale (CGI-I), CGI-Severity scale (CGI-S), Sheehan Disability Scale (SDS), and Hamilton Anxiety Rating Scale (HAM-A) scores were significantly greater in the duloxetine group than in the vortioxetine group. The incidence of treatment-emergent adverse events was significantly higher in the duloxetine group than in the vortioxetine group. Conclusion: Duloxetine was more effective but less well-tolerated than vortioxetine in MDD. Considering the potential limitations of this meta-analysis, more large-scale RCTs are needed to confirm these findings.
- [Show abstract] [Hide abstract] ABSTRACT: Background and objectives: Ilaprazole is a novel proton pump inhibitor that provides effective and long lasting inhibition of intragastric acid secretion. The objectives of this study were to investigate the pharmacokinetics, pharmacodynamics, and safety of intravenous ilaprazole after multiple administrations in healthy Chinese subjects. Methods: This was an open-label and multiple-dose clinical study. Ten healthy Chinese subjects received 10 mg ilaprazole infusion once daily for 5 days. Helicobacter pylori status was examined. Blood samples were collected and intragastric pH was recorded for 24 h. Safety was assessed throughout the study. Results: There was no accumulation after multiple administrations. The mean steady-state half-life and clearance were comparable to those following single administration. Ilaprazole provided sustainable and significant intragastric pH control in terms of percentage time at pH >4, pH >6 within 24 h and mean 24-h pH values. The pH value within 24 h was affected by Helicobacter pylori infection in subjects with continuous infusion. Intravenous ilaprazole was safe and there were no serious adverse events. Conclusion: Intravenous ilaprazole provided stable pharmacokinetics and pharmacodynamics at a dose of 10 mg once daily for 5 days, and was well tolerated in healthy subjects.
- [Show abstract] [Hide abstract] ABSTRACT: Fentanyl buccal soluble film (Onsolis(®), Breakyl(®), Painkyl™) comprises two layers: a mucoadhesive layer containing the active drug, and an inactive layer with the aim of preventing the diffusion of fentanyl into the oral cavity. It is approved in several countries worldwide, including the USA and those of the EU, for the management of breakthrough cancer pain in opioid-tolerant, adult patients with cancer. This article reviews the pharmacological properties of fentanyl buccal soluble film and its clinical efficacy and tolerability in these patients. Fentanyl buccal soluble film provides an additional option for transmucosal delivery of fentanyl, with approximately half of the dose undergoing an initial, rapid absorption via the buccal mucosa (accounting for its high bioavailability). In clinical trials, fentanyl buccal soluble film was associated with significant improvements in pain intensity scores versus placebo and was generally well tolerated. The most common adverse events were typical opioid-associated adverse events, such as nausea and vomiting. Fentanyl buccal soluble film is a useful option for the treatment of breakthrough cancer pain in opioid-tolerant patients.
- [Show abstract] [Hide abstract] ABSTRACT: Background and objective: Once-weekly glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a novel class of injectable antidiabetic drugs. Previous studies indicated that GLP-1RAs (exenatide and liraglutide) might increase the incidence of pancreatitis and pancreatic cancer. Here, we evaluated the clinical safety of once-weekly GLP-1RAs with respect to tumour risk. Methods: Relevant studies were selected from ClinicalTrials.gov. Randomized controlled trials that reported the incidences of neoplasms were included in our research. Outcomes were calculated as the risk ratio using the Mantel-Haenszel method and fixed-effects model. Results: Our analysis included 26 randomized controlled trials with 16,090 patients. Once-weekly GLP-1RAs did not increase the risk for tumours compared with other antidiabetic drugs [risk ratio (RR), 1.02; 95 % confidence interval (CI), 0.74-1.41; p = 0.91]; this finding was independent of the type of GLP-1RA administered (albiglutide, exenatide extended-release and dulaglutide) and duration of the trials (limited to ≥52 weeks). Subgroup analyses revealed that once-weekly GLP-1RAs did not increase tumour risk compared with placebos, exenatide and liraglutide, insulin or oral drugs. Additionally, once-weekly GLP-1RAs did not increase tumour risk in any tissue. Conclusions: Compared with other antidiabetic drugs, once-weekly GLP-1RAs did not increase the risk for any tumour, and this finding was independent of the type of GLP-1RA administered and treatment duration. However, our study had many limitations, and further longer term trials with larger samples should be conducted in future to confirm our results.
- [Show abstract] [Hide abstract] ABSTRACT: Background and objectives: No head-to-head clinical trials are available to help physicians in the decision-making process of first-line therapy in poor-prognosis metastatic renal cell carcinoma (RCC). The objectives of our study were to identify experts' prescribing practices and to review available clinical data in first-line therapies for poor-prognosis metastatic RCC (mRCC). Methods: Thirteen RCC experts were asked to fill in a self-administered questionnaire evaluating prescribing practices. A systematic review was performed in July 2015 in MEDLINE for clinical trials evaluating first-line strategy in poor-prognosis mRCC. Results: Ten out of 13 experts completed the questionnaire (76.9 %). Sunitinib was the most frequently prescribed first-line therapy (8/10; 80 %). The main reason for prescribing sunitinib most frequently was the evidence of effectiveness for the majority (5/8 experts). A total of 21 articles were found suitable. Only one phase III randomized controlled trial in which all patients had a poor prognosis was retrieved. Temsirolimus increases progression-free survival and overall survival compared to IFN-alpha. Increased PFS with sunitinib in poor-prognosis patients was shown in a subgroup analysis of the pivotal trial. An expanded-access trial confirmed this result. Discussion: Experts tend to prefer sunitinib as first-line therapy even in poor-prognosis mRCC. In light of the systematic review, no targeted therapy appears to be more effective than another. The upcoming challenge is to discover more effective new drugs since the overall survival of poor-prognosis mRCC still remains extremely limited.
- [Show abstract] [Hide abstract] ABSTRACT: Background and objectives: 5-hydroxytryptamine3 (5-HT3) receptor antagonists have been commonly used to reduce propofol injection pain. The aim of this meta-analysis was to evaluate the efficacy and safety of 5-HT3 receptor antagonists in decreasing the incidence and intensity of propofol injection pain. Methods: Online databases of Pubmed, Embase and the Cochrane Central Register of Controlled Trials were searched as well as reference lists of included studies and recent reviews. Eligible randomized controlled trials (RCTs) assessing the efficacy and safety of 5-HT3 receptor antagonists for propofol injection pain were identified. The outcomes included the incidence and intensity of propofol injection pain and adverse effects. We calculated risk ratios (RR) with 95 % confidence intervals (CIs) for dichotomous data and adopted fixed or random-effects model when proper. Results: A total of eight RCTs were included in the final analysis. Compared with the control group, 5-HT3 receptor antagonists were related to a decreasing incidence of propofol injection pain (RR 0.43, 95 % CI 0.33-0.56, P < 0.05). Besides, they also effectively alleviated the severity of propofol injection pain. They significantly reduced the number of patients with moderate (RR 0.21, 95 % CI 0.15-0.30, P < 0.05) and severe pain (RR 0.16, 95 % CI 0.10-0.25, P < 0.05) during propofol injection. 5-HT3 receptor antagonists and lidocaine were equally effective in preventing propofol injection pain. Moreover, only one article mentioned the adverse effects of 5-HT3 receptor antagonists in two patients. Conclusion: Our meta-analysis indicates that 5-HT3 receptor antagonists can effectively reduce the incidence and severity of propofol injection pain. Additionally, 5-HT3 receptor antagonists may become the alternatives to lidocaine in attenuating propofol injection pain. However, evidence is still limited for the safety of 5-HT3 receptor antagonists on propofol injection pain.
- [Show abstract] [Hide abstract] ABSTRACT: Background and objectives: Modified-release drugs may provide clinical advantages compared to immediate-release forms and improve convenience to the patient and health outcomes. Concerns have been raised regarding interchangeability, efficacy, and safety of modified-release formulations. This study analyses all US Food and Drug Administration (FDA)-approved modified-release formulations and market trends, and illustrates how bioequivalence and safety of generic modified-release products compare to their respective brand name drugs and other generic drugs with different formulation design characteristics. This study also examines major concerns related to modified-release formulations: safety of opioids and bioequivalence of generic bupropion and methylphenidate. Methods: Study data were derived from the FDA electronic versions of the FDA's Orange Book (OB) and the FDA safety communications web page. Medicare Part D utilization and expenditures data were extracted from the Centers for Medicare and Medicaid. Results: In May 2015, 276 (11.9 %) of the 2325 active ingredients and fixed-dose combinations listed in the FDA's Orange Book had at least one modified-release form approved by the FDA. The number of approvals increased over time; 52.5 % of modified releases were approved in the period 2000-May 2015. The FDA required a risk evaluation and mitigation strategy (REMS) to ensure that the benefits of extended-release opioids outweighed its risks of overdose and abuse. The REMS involved 16 new drug applications and 25 abbreviated new drug applications. Conclusions: The FDA addressed interchangeability problems with generic modified-release alternatives of bupropion and methylphenidate including lack of bioequivalence, reduced efficacy, and increased incidence of adverse events. Systematic post-marketing surveillance studies are needed to assess differences in safety, interchangeability, and efficacy of drugs with modified- and immediate-release formulations.
- [Show abstract] [Hide abstract] ABSTRACT: Background and objectives: Sore throat, cough, and hoarseness are the common and severe complications after general anesthesia with tracheal intubation. The efficacy of prophylactic administration of corticosteroids in reducing the incidence of postoperative complications is controversial. Thus, we conducted a meta-analysis to assess the effects of corticosteroids in the prevention of postoperative complications. Methods: A comprehensive literature search of Pubmed, Embase, and Web of Science was conducted to identify relative trials. Eligible studies were randomized controlled trials (RCTs) that assessed the effect of corticosteroids for preventing postoperative complications. The outcomes included the prevalence of postoperative sore throat, cough, hoarseness, laryngeal edema, and reintubation. A random-effects or fixed-effects model was used to pool the estimates, according to the heterogeneity among the included studies. Results: Eighteen RCTs with a total of 2685 patients were included in this meta-analysis. Pooled estimates showed that corticosteroids significantly reduced the incidence of postoperative sore throat, hoarseness, and cough. Moreover, corticosteroids had a positive effect on the incidence of laryngeal edema and reintubation. Subgroup analysis showed that corticosteroids significantly decreased the incidence of severe sore throat and hoarseness, but not cough. Conclusion: Evidence from this meta-analysis of 18 RCTs indicated that prophylactic administration of corticosteroids is not only effective in reducing the incidence and severity of postoperative sore throat and hoarseness, but also the incidence of laryngeal edema and reintubation.
- [Show abstract] [Hide abstract] ABSTRACT: Background Avibactam is a non-β-lactam β-lactamase inhibitor that restores the in vitro activity of β-lactams, such as ceftazidime, against bacterial pathogens harboring Ambler class A, C, and some class D β-lactamases. Objective This randomized, double-blind, placebo-controlled, phase I study (NCT01920399) evaluated the safety, tolerability, and pharmacokinetics of single and repeated doses of avibactam and ceftazidime in healthy Chinese subjects. Methods Sixteen healthy Chinese males aged 18–45 years were randomized 3:1 to receive 2000 mg ceftazidime and 500 mg avibactam (n = 12) or matched placebo (n = 4) as a 120-min intravenous infusion, once on Days 1 and 9, and every 8 h on Days 2–8. Results Avibactam and ceftazidime showed time-independent pharmacokinetics. Plasma exposure to avibactam and ceftazidime was similar following single and multiple dosing and accumulation of either agent was negligible. The majority of the avibactam and ceftazidime dose was recovered in urine. Adverse events were reported in three subjects (25.0 %) in the ceftazidime-avibactam group and one subject (25.0 %) in the placebo group. Two subjects in the ceftazidime-avibactam group had elevations in transaminases and one subject in the placebo group had elevated serum bilirubin levels that were considered causally related to study treatment. All adverse events were of mild intensity. Conclusions Single and multiple doses of 2000 mg ceftazidime and 500 mg avibactam were well tolerated in healthy Chinese subjects, and the observed pharmacokinetics were comparable to previous studies conducted in Western subjects.
- [Show abstract] [Hide abstract] ABSTRACT: Background and objectives: Ramucirumab is a fully immunoglobulin G (lgG) monoclonal antibody targeting vascular endothelial growth factor receptor type 2 (VEGFR2). Previous clinical trials suggested ramucirumab could improve the survival and increase the risk of adverse effects. Here, we aimed to assess the efficacy and safety of ramucirumab in the treatment of advanced solid tumors. Methods: Publications were searched from Pubmed, Embase database and clinicaltrials.gov. Hazard ratio (HR) and 95 % confidence interval (95 % CI) were calculated to evaluate efficacy, and the risk ratio (RR) for adverse effects. Results: Ten relevant studies were included. Ramucirumab resulted in significant benefit in overall survival [OS, HR and 95 % CI 0.87 (0.82-0.93), I (2): 0.0 %] and progression-free survival [PFS, HR and 95 % CI 0.74 (0.66-0.82), I (2): 67.4 %]. Also the difference of time to progression (TTP) and objective response rate (ORR) between two groups were also significant [0.70 (0.57-0.88) and 1.78 (1.40-2.25), respectively]. Ramucirumab could increase the risk of total adverse effects (TAEs, of any grade) by 1 % (from 0 to 2 %) and severe adverse effects (SAEs, grade > 2) by 17 % (from 9 to 26 %). The most frequently occurring TAEs were fatigue (54.71 %), neutropenia (42.74 %), bleeding (37.55 %), nausea (34.63 %) and stomatitis (33.74 %). Most frequently occurring SAEs (grade ≥3) were neutropenia (33.43 %), fatigue (12.08 %), leukopenia (10.59 %), hypertension (8.99 %) and liver injury (8.74 %). Conclusion: Ramucirumab could improve OS and PFS for patients suffering from advanced solid tumors. Ramucirumab could increase the risk of TAEs and SAEs.
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