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Aims: Cladribine tablets have shown significant efficacy for the treatment of relapsing multiple sclerosis, a chronic and debilitating immune‐mediated disorder. This study was conducted to examine acute and/or cumulative effects of cladribine tablets 10 mg (3.5 or 5.25 mg/kg cumulative dose over 2 years) on heart rate, AV conduction and cardiac repolarization in patients with relapsing–remitting multiple sclerosis (RRMS). Methods: CLARITY was a 96‐week, double‐blind, placebo‐controlled, multicentre trial which evaluated the safety and efficacy of cladribine tablets 3.5 and 5.25 mg/kg body weight in patients with RRMS. A total of 135 patients were included in the ECG substudy, providing a total of 1534 post‐dose ECGs. ECG data were collected 15 minutes pre‐dose and between 0.5 and 3 hours post‐dose at pre‐study evaluation, study Day 1 and Weeks 5, 9, 13, 48 and 52. Results: For cladribine tablets 3.5 mg/kg, the maximum change in placebo‐adjusted post‐dose QTcF vs. visit‐baseline (BL) was −0.42 ms (90% CI: −3.61–4.44) at Week 1 (acute effects), and 3.20 ms (90% CI: −0.08–6.33) for cladribine tablets 5.25 mg/kg. The greatest observed differences in post‐dose QTcF vs. study BL occurred at Week 48 for both the 3.5 and 5.25 mg/kg doses of cladribine tablets with 5.99 ms (90% CI: 0.53–11.44) and 8.74 ms (90% CI: 3.18–14.31), respectively. No significant changes were observed in T‐wave morphology in either treatment group. Conclusions: Cladribine tablets 3.5 mg/kg (approved dose in Europe/other regions) did not confer clinically meaningful effects on heart rate, AV conduction and ventricular repolarization. [ABSTRACT FROM AUTHOR]

Drug-induced prolongation of the QT interval on the electrocardiogram (ECG) infrequently results in Torsades de pointes, a potentially fatal arrhythmia. Therefore, thorough QT analysis of new drugs is a regulatory requirement. The objective of this phase 1 study was to assess the effects of oral tedizolid phosphate on the QT interval corrected with Fridericia's formula (QTcF) in healthy adult subjects. A single therapeutic dose (200 mg) and a supratherapeutic dose (1200 mg) of tedizolid phosphate were administered to characterise QTc changes following typical systemic exposure and with markedly higher exposures, respectively. This was a four-way crossover study with 48 subjects randomly assigned to receive therapeutic and supratherapeutic doses of tedizolid phosphate, moxifloxacin (positive control for QT interval prolongation) and placebo (negative control). A continuous 12-lead ECG was recorded from 1 h before drug administration to 23 h after administration. Adverse events, which were generally mild, occurred most frequently with moxifloxacin or with a supratherapeutic dose of tedizolid phosphate; however, all treatments were well tolerated. This study demonstrated that therapeutic or supratherapeutic doses of the antibacterial tedizolid had no clinically significant effect on QT interval in healthy adults [ ClinicalTrials.gov registration no.: NCT01461460]. [ABSTRACT FROM AUTHOR]

The article offers the author's insights on the importance of the electronic informed consent, which is a key to support patient-centric mantra in clinical trials. Topics discussed include the guidance on informed consent published by the U.S. Food and Drug Administration (FDA), various recommendations to obtain patient agreement which include clinical trials description, treatment benefits, and confidentiality, and the significance of language on patient's understanding on informed consent.

Research performance is a critical component of the understanding of university prestige, yet measuring it is complex. This paper proposes using ‘real dollars of research expenditures per article published’ as a measure of research productivity because it is more accurate than other quantitative measures of research productivity, including ‘articles published per capita,’ for certain applications, especially financial and economic analyses. In tracking this measure, a decline in the research productivity of US colleges and universities was observed during the period 1996 to 2002. [ABSTRACT FROM PUBLISHER]

Canada's research policy has aimed to facilitate technology transfer from universities and induce innovation in industry for the past three decades. This article examines the policy instruments currently employed by the federal government in Canada to stimulate university-industry research linkages. First, the article examines the national landscape of industry R&D and its interface with university research. Then, multiple policy instruments are identified, and their goals and functions are examined. Finally, the article discusses the main features and implications of Canada's policy approach. [ABSTRACT FROM AUTHOR]

The article discusses the importance of electrocardiogram (ECG) reading on clinical research and practice. It stresses that it is critical in data collection during clinical research with the investigational drug's cardiac safety profile, especially the interval duration measurements of heart activity, emphasizing ECG centralization. It suggests that relevance of the findings should also be associated with one's prior history and current health status.

A prestigious reputation is the primary success factor in higher education because it attracts resources necessary to sustain growth. Among research-intensive universities (RIUs), research performance is a key driver of institutional reputation. Achieving an accelerating rate of growth of research performance is the desired objective of all RIUs which, in turn, is contributing to intensification in the competition for research funds. In competitive environments, the use of strategy is widely used to enhance competitive effectiveness. The question arises as to whether some expressions of strategy are more closely associated with increased research performance than others? This paper provides insight into this question by presenting a model demonstrating that the strategic emphases of individual RIUs in the USA are highly correlated to changes in the shares of federally financed research funding actually realized by the institutions. [ABSTRACT FROM AUTHOR]

The article discusses the implication of electrocardiography (ECG) in the development of drugs as well as the use of laboratories. According to the article, ECGs are used to gather information as well as assess the effect of investigational drugs on the electrical functions of the heart. In addition, it states that sponsors should consider several factors such as reducing the price they pay for research since it does not give them the assurance that all the results are correct. INSET: Homework for Sponsors.

Purpose: Cardiac dysfunction, particularly QT interval prolongation, has been observed with tyrosine kinase inhibitors approved to treat chronic myeloid leukemia. This study examines the effects of ponatinib on cardiac repolarization in patients with refractory hematological malignancies enrolled in a phase 1 trial. Methods: Electrocardiograms (ECGs) were collected at 3 dose levels (30, 45, and 60 mg) at 6 time points. Electrocardiographic parameters, including QTc interval, were measured, and 11 morphological analyses were conducted. Central tendency analyses of ECG parameters were performed using time-point and time-averaged approaches. All patients with at least 2 baseline ECGs and 1 on-treatment ECG were included in the analyses. Patients with paired ECGs and plasma samples were included in the pharmacokinetic/pharmacodynamic analysis to examine the relationship between ponatinib plasma concentration and change from baseline in QT intervals. Results: Thirty-nine patients at the 30-, 45-, and 60-mg dose levels were included in the central tendency and morphological analyses. There was no significant effect on cardiac repolarization, as evidenced by non-clinically significant mean QTcF changes from baseline of −10.9, −3.6, and −5.0 ms for the 30-, 45-, and 60-mg dose levels, respectively. The morphological analysis revealed 2 patients with atrial fibrillation and 2 with T wave inversion. Seventy-five patients were included in the pharmacokinetic/pharmacodynamic analysis across all dose levels. The slope of the relationship for QTcF versus plasma ponatinib concentration was not positive (−0.0171), indicating no exposure-effect relationship. Conclusions: Ponatinib is associated with a low risk of QTc prolongation in patients with refractory hematological malignancies. [ABSTRACT FROM AUTHOR]

This study investigated the effect of eslicarbazepine acetate (ESL) on cardiac repolarization in healthy adult volunteers. A randomized, placebo/active-controlled, 4-period crossover study was conducted in 67 participants. In 3 periods, participants received once-daily doses of ESL 1200 mg, ESL 2400 mg, and placebo for 5 days; in 1 period, participants received placebo on days 1 to 4 and a 400-mg moxifloxacin single dose on day 5. In each period, 24-hour 12-lead Holter monitoring was performed on days –1 (baseline) and 5. There was no clinically relevant effect of ESL 1200 mg and 2400 mg versus placebo on cardiac depolarization or repolarization as measured by the QRS or QTc intervals, respectively. Mean PR interval increased following ESL 1200 mg and 2400 mg, but there was no participant with a PR interval above the upper limit of the normal range (200 ms). The upper bound of the 95% confidence interval for the placebo-corrected change from baseline of the individually corrected QT interval (QTcI) following administration of ESL 1200 mg and ESL 2400 mg was <10 ms at every time point. Moxifloxacin caused an increase in QTcI above the 10-ms threshold for clinical significance at several time points, demonstrating assay sensitivity. It is concluded that administration of ESL 1200 mg and ESL 2400 mg did not induce a clinically significant prolongation of the QTcI interval. [ABSTRACT FROM PUBLISHER]

The article discusses the scientific approach in the centralization of electrocardiogram (ECG) Phase III on cardiac safety risk assessment. It emphasizes the QT wave interval prolongation, or the contraction and repolarization of cardiac muscles, on polymorphic ventricular tachycardia or torsades de pointes during drug interaction. The clinical trial "Thorough QT/QTc (TQT) Study" promotes cardiac safety data collection associated with market drugs and further enhances assessment.

The objective of this study was to establish effects of liraglutide on the QTc interval. In this randomized, placebocontrolled, double-blind crossover study, 51 healthy participants were administered placebo, 0.6, 1.2, and 1.8 mg liraglutide once daily for 7 days each. Electrocardiograms were recorded periodically over 24 hours at the end of placebo and highest dosing periods. Four different models for QT correction were used: QTci, as the primary endpoint, and QTciL, QTcF, and QTcB as secondary endpoints. The upper bound of the 1-sided 95% confidence interval for time-matched, baseline-corrected, placebo-subtracted QTc intervals was <10 ms for all 4 correction methods. Moxifloxacin (400 mg) increased QTc intervals by 10.6 to 12.3 ms at 2 hours. There was no concentration-exposure dependency on QTc interval changes by liraglutide and no QTc thresholds above 500 ms or QTc increases >60 ms. The authors conclude that liraglutide caused no clinically relevant increases in the QTc interval. [ABSTRACT FROM AUTHOR]