Cardiovascular Function in Nonclinical Drug Safety Assessment

2011 ◽  
Vol 30 (3) ◽  
pp. 272-286 ◽  
Author(s):  
R. Dustan Sarazan ◽  
Scott Mittelstadt ◽  
Brian Guth ◽  
John Koerner ◽  
Joanne Zhang ◽  
...  
Keyword(s):  
Safety Assessment ◽  
Development Process ◽  
Drug Effects ◽  
Cardiovascular Effects ◽  
Pharmaceutical Companies ◽  
Consumer Market ◽  
Safety Issues ◽  
Patient Health ◽  
Related Drug ◽  
Clinically Significant

There are several recent examples where clinically significant, safety-related, drug effects on hemodynamics or cardiac function were not apparent until large clinical trials were completed or the drugs entered the consumer market. Such late-stage safety issues can have significant impact on patient health and consumer confidence, as well as ramifications for the regulatory, pharmaceutical, and financial communities. This manuscript provides recommendations that evolved from a 2009 HESI workshop on the need for improved translation of nonclinical cardiovascular effects to the clinical arena. The authors conclude that expanded and improved efforts to perform sensitive yet specific evaluations of functional cardiovascular parameters in nonclinical studies will allow pharmaceutical companies to identify suspect drugs early in the discovery and development process while allowing promising drugs to proceed into clinical development.

scholarly journals Prescription Data Mining and the Protection of Patients' Interests

2010 ◽  
Vol 38 (1) ◽  
pp. 74-84 ◽  
Author(s):  
David Orentlicher
Keyword(s):  
Data Mining ◽  
Medical Care ◽  
Medical Literature ◽  
Direct Marketing ◽  
Pharmaceutical Companies ◽  
Prescription Data ◽  
Sales Representatives ◽  
Patient Health ◽  
Drug Detailing

Pharmaceutical companies have long relied on direct marketing of their drugs to physicians through one-on-one meetings with sales representatives. This practice of “detailing” is substantial in its costs and its number of participants. Every year, pharmaceutical companies spend billions of dollars on millions of visits to physicians by tens of thousands of sales representatives.Critics have argued that drug detailing results in sub-optimal prescribing decisions by physicians, compromising patient health and driving up spending on medical care. In this view, physicians often are unduly influenced both by marketing presentations that do not accurately reflect evidence from the medical literature and by the gifts that sales representatives deliver in conjunction with their presentations.

Short- and Long-Term Cardiovascular Effects of Mixed Amphetamine Salts Extended-Release in Adolescents With ADHD

CNS Spectrums ◽  
2005 ◽  
Vol 10 (S15) ◽  
pp. 22-30 ◽  
Author(s):  
Timothy E. Wilens ◽  
Thomas J. Spencer ◽  
Joseph Biederman
Keyword(s):  
Extended Release ◽  
Cardiovascular Effects ◽  
Dose Titration ◽  
Open Label ◽  
Double Blind ◽  
Once Daily ◽  
Open Label Extension ◽  
Short And Long Term ◽  
Clinically Significant

AbstractObjectiveAssess cardiovascular effects of once-daily mixed amphetamine salts extended release (MAS XR) in adolescents (13–17 years of age) with attention-deficit/hyperactivity disorder (ADHD).MethodsBlood pressure (BP), pulse, and electrocardiograms were assessed in 327 healthy subjects during a 4-week, randomized, double-blind, placebo-controlled, forced dose-titration study. Placebo (n=69) or once-daily MAS XR(10, 20, 30, or 40 mg) was administered to subjects ≤75 kg (n=233); 50- and 60-mg MAS XR was administered to subjects >75 kg (n=25). One hundred thirty-eight subjects participated in a 6-month, open-label extension study.FindingsChanges in BP and QTcB (Bazett's formula) intervals at 4 weeks with MAS XR were not significantly different from the placebo group. Pulse increased by 5.0 and 8.5 bpm after 3 weeks with MAS XR 20 and 50 mg/day, respectively (P≤.002). After 6 months of open-label MAS XR treatment, mean increases in systolic BP (1.7 mm Hg; P=.0252) and pulse (4.4 bpm; P<.0001) were statistically, but not clinically, significant diastolic BP was not significantly changed (0.6 mm Hg) A decrease in QTcB interval (-4.6±19.9 msec) was statistically (P=.009), but not clinically, significant. There were no serious cardiovascular adverse events.ConclusionCardiovascular effects of short- and long-term MAS XR treatment (≤60 mg/day) were minimal in otherwise healthy adolescents with ADHD.

scholarly journals Pharmacogenetics in drug development

2005 ◽  
Vol 360 (1460) ◽  
pp. 1579-1588 ◽  
Author(s):  
Alun D McCarthy ◽  
James L Kennedy ◽  
Lefkos T Middleton
Keyword(s):  
Pharmaceutical Companies ◽  
Efficacy And Safety ◽  
Plasma Drug ◽  
Dose Selection ◽  
Drug Discovery And Development ◽  
Safety Issues ◽  
Drug Choice ◽  
Probability Of Success ◽  
Safety Studies ◽  
Appropriate Therapy

Over the last two decades, identification of polymorphisms that influence human diseases has begun to have an impact on the provision of medical care. The promise of genetics lies in its ability to provide insights into an individual's susceptibility to disease, the likely nature of the disease and the most appropriate therapy. For much of its history, pharmacogenetics (PGx—the use of genetic information to impact drug choice) has been limited to comparatively simple phenotypes such as plasma drug levels. Progress in genetics technologies has broadened the scope of PGx efficacy and safety studies that can be implemented, impacting on a broad spectrum of drug discovery and development activities. Recent PGx data show the ability of this approach to generate information that can be applied to dose selection, efficacy determination and safety issues. This in turn will lead to significant opportunities to affect both the approach to clinical development and the probability of success—the latter being an important aspect for pharmaceutical companies and for the patients who will benefit from these new medicines.

scholarly journals What Lies Beneath: Exploring Different Depressive Symptoms Across Selected Risk Factors in Icelandic Team Sport Athletes

2021 ◽  
Vol 15 (1) ◽  
pp. 54-79
Author(s):  
Richard Tahtinen ◽  
Hafrun Kristjansdottir ◽  
Daniel T. Olason ◽  
Robert Morris
Keyword(s):  
Depressive Symptoms ◽  
Depressed Mood ◽  
Team Sport ◽  
Depressive Symptomology ◽  
Symptoms Of Depression ◽  
Patient Health ◽  
Emotional Aspects ◽  
Clinically Significant ◽  
Core Symptoms ◽  
Specific Symptoms

The aim of the study was to explore the prevalence of specific symptoms of depression in athletes and to test differences in the likelihood of athletes exhibiting these symptoms across age, sex, type of team sport, and level of competition. A sample of Icelandic male and female team sport athletes (N = 894, 18–42 years) was included in the study. Of the athletes exhibiting clinically significant depressive symptoms on the Patient Health Questionnaire-9, 37.5% did not exhibit core symptoms of depression. Compared with males, females were significantly more likely to exhibit depressed mood, feelings of worthlessness/guilt, and problems with sleep, fatigue, appetite, and concentration. Within males, differences were mostly related to neurovegetative aspects of depression (sleep and appetite), whereas in females, differences were related to cognitive/emotional aspects (e.g., depressed mood, guilt/worthlessness). The findings underline the importance of exploring specific symptoms of depression to provide a richer understanding of depressive symptomology in athletes.

scholarly journals Pharmacogenomics- The Promise of Personalized Medicine

2013 ◽  
Vol 12 (4) ◽  
pp. 346-356 ◽  
Author(s):  
M Fakruddin ◽  
A Chowdhury
Keyword(s):  
Side Effects ◽  
Personalized Medicine ◽  
Development Process ◽  
Genetic Basis ◽  
Ethical Issues ◽  
Medical Science ◽  
Medical Community ◽  
Pharmaceutical Companies ◽  
Current Therapies ◽  
Genetic Makeup

Introduction: Pharmacogenomics (PGx) is the study of the genetic basis of variability among individuals in response to drugs. It is the newest discipline of medicine and is becoming a very active area of research, with the pharmaceutical industry gaining experience applying it, integrating it into the drug development process, and also learning to better manage the expectations of the medical community. Methodology: A comprehensive review of the literature on the principles, applications, challenges and prospects of pharmacogenomics was performed. Results: Pharmacogenomics tailors therapies to the genetic makeup of an individual and can therefore offer treatments that are more efficacious and have fewer side effects. Despite these benefits, personalized medicine has not been embraced by large pharmaceutical companies. It is expected that the first wave of successful pharmacogenomics products will be used in acute treatments for which current therapies have and severe side effects. These products should also be good candidates for premium pricing. Personalized medicine (PM), based on the genetic makeup of a patient, may result in not only an improved therapeutic response but also a clinically important reduction in adverse drug reactions. The experience to date is mixed, with a few successes but many frustrations. Conclusion: However, for pharmacogenomics to be truly embraced, the benefits of this technology must become more widely accepted in terms of economic, public, regulatory and ethical issues. DOI: http://dx.doi.org/10.3329/bjms.v12i4.11041 Bangladesh Journal of Medical Science Vol. 12 No. 04 October ’13 Page 346-356

IO, Coagency, Intractability, and Resilience

2013 ◽  
pp. 342-352 ◽  
Author(s):  
Erik Hollnagel
Keyword(s):  
Safety Assessment ◽  
Assessment Methods ◽  
Resilience Engineering ◽  
Safety Issues ◽  
Technological Developments ◽  
Technical Systems ◽  
Integrated Operations ◽  
Circulus Vitiosus

Technological developments continuously create opportunities that are eagerly adopted by industries with a seemingly insatiable need for innovation. This has established a forceful circulus vitiosus that has resulted in exceedingly complicated socio-technical systems. The introduction of Integrated Operations in drilling and off-shore operations is one, but not the only, example of that. This development poses a challenge for how to deal with risk and safety issues. Where existing safety assessment methods focus on descriptions of component capabilities, complicated socio-technical systems must be described in terms of relations or even functional couplings. In order to design, analyse, and manage such systems, it must be acknowledged that performance adjustments are a resource rather than a threat. Safety can no longer be achieved just by preventing that something goes wrong, but must instead try to ensure that everything goes right. Resilience engineering provides the conceptual and practical means to support and accomplish that change.

Daily intake of soft drinks is associated with symptoms of anxiety and depression in Chinese adolescents

2019 ◽  
Vol 22 (14) ◽  
pp. 2553-2560 ◽  
Author(s):  
Xingyu Zhang ◽  
Xiaoyan Huang ◽  
Yi Xiao ◽  
Danrong Jing ◽  
Yuzhou Huang ◽  
...  
Keyword(s):  
Soft Drink ◽  
Daily Intake ◽  
Cross Sectional Study ◽  
Soft Drinks ◽  
Mediation Effect ◽  
Anxiety And Depression ◽  
Cross Sectional ◽  
Soft Drink Consumption ◽  
Patient Health ◽  
Clinically Significant

AbstractObjective:The association of soft drink consumption with mental problems in Asian adolescents has not been reported. The present study aimed to investigate the association of soft drink consumption and symptoms of anxiety and depression in adolescents in China.Design:A cross-sectional study to investigate the association of intake of soft drinks and sugars from soft drinks with symptoms of anxiety and depression measured by the two-item Generalized Anxiety Disorder (GAD-2) and the Patient Health Questionnaire (PHQ-2), respectively.Setting:A comprehensive university in Changsha, China.Participants:Newly enrolled college students in 2017.Result:In total, 8226 students completed the investigation and 8085 students with no systemic disorders were finally analysed. Students consuming soft drinks ≥7 times/week had significantly higher (mean difference; 95 % CI) GAD-2 (0·15; 0·07, 0·23) and PHQ-2 (0·27; 0·19, 0·35) scores compared with those barely consuming soft drinks, adjusted for demographic and behavioural factors. Those consuming &gt;25 g sugar/d from soft drinks had significantly higher GAD-2 (0·11; 0·04, 0·18) and PHQ-2 (0·22; 0·15, 0·29) scores compared with non-consumers. The mediation effect of obesity in the associations was not clinically significant.Conclusions:Adolescents consuming soft drinks ≥7 times/week, or &gt;25 g sugar/d from soft drinks, had significantly higher levels of anxiety and depression. Dietary suggestion is needed to prevent anxiety and depression in adolescents.

scholarly journals Failures to further developing orphan medicinal products after designation granted in Europe: an analysis of marketing authorisation failures and abandoned drugs

BMJ Open ◽  
2017 ◽  
Vol 7 (9) ◽  
pp. e017358 ◽  
Author(s):  
Viviana Giannuzzi ◽  
Annalisa Landi ◽  
Enrico Bosone ◽  
Floriana Giannuzzi ◽  
Stefano Nicotri ◽  
...  
Keyword(s):  
Marketing Authorisation ◽  
Development Process ◽  
Developmental Process ◽  
Clinical Stage ◽  
Phase Iii ◽  
Marketing Approval ◽  
Medicinal Products ◽  
Safety Issues ◽  
Stage Of Development ◽  
Orphan Medicinal Products

ObjectivesThe research and development process in the field of rare diseases is characterised by many well-known difficulties, and a large percentage of orphan medicinal products do not reach the marketing approval.This work aims at identifying orphan medicinal products that failed the developmental process and investigating reasons for and possible factors influencing failures.DesignDrugs designated in Europe under Regulation (European Commission) 141/2000 in the period 2000–2012 were investigated in terms of the following failures: (1) marketing authorisation failures (refused or withdrawn) and (2) drugs abandoned by sponsors during development.Possible risk factors for failure were analysed using statistically validated methods.ResultsThis study points out that 437 out of 788 designations are still under development, while 219 failed the developmental process. Among the latter, 34 failed the marketing authorisation process and 185 were abandoned during the developmental process. In the first group of drugs (marketing authorisation failures), 50% reached phase II, 47% reached phase III and 3% reached phase I, while in the second group (abandoned drugs), the majority of orphan medicinal products apparently never started the development process, since no data on 48.1% of them were published and the 3.2% did not progress beyond the non-clinical stage.The reasons for failures of marketing authorisation were: efficacy/safety issues (26), insufficient data (12), quality issues (7), regulatory issues on trials (4) and commercial reasons (1). The main causes for abandoned drugs were efficacy/safety issues (reported in 54 cases), inactive companies (25.4%), change of company strategy (8.1%) and drug competition (10.8%). No information concerning reasons for failure was available for 23.2% of the analysed products.ConclusionsThis analysis shows that failures occurred in 27.8% of all designations granted in Europe, the main reasons being safety and efficacy issues. Moreover, the stage of development reached by drugs represents a specific risk factor for failures.

Prevalence of depressive symptoms and associated factors in an urban, ophthalmic population

2020 ◽  
pp. 112067212090170 ◽  
Author(s):  
Eileen L Mayro ◽  
Ann P Murchison ◽  
Lisa A Hark ◽  
Marlee Silverstein ◽  
Olivia Y Wang ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Depressive Symptoms ◽  
Odds Ratio ◽  
Low Vision ◽  
Adult Patients ◽  
Patient Health Questionnaire ◽  
Health Questionnaire ◽  
Diabetes Status ◽  
Patient Health ◽  
Clinically Significant

Objective: To determine the prevalence of depressive symptoms in an adult ophthalmic patient population and to delineate correlates. Design: Cross-sectional study. Participants: Adult patients (⩾18 years) were approached in general and sub-specialty cornea, retina, and glaucoma ophthalmic clinics. A total of 367 patients from the four clinics were enrolled. Methods: Depressive symptoms were assessed using the Patient Health Questionnaire-9. A cut-off score of ⩾10 was used to indicate clinically significant depressive symptoms. Patient Health Questionnaire-9 scores were used to evaluate bivariate relationships between depressive symptoms and distance visual acuity, ocular diagnosis, diabetes status, smoking status, demographic information, and medications. Results: The majority of patients were female (52.9%) and Caucasian (48.6%). The mean age was 52.0 years (standard deviation: 16.7). Clinically significant depressive symptoms were present in 19.9% of patients overall; this rate varied slightly by clinic. Patients with low vision and blindness (visual acuity worse than 20/60) were more likely to have depressive symptoms (odds ratio = 2.82; 95% confidence interval: 1.90–4.21). Smoking and diabetes were also associated with depressive symptoms (odds ratio = 3.11 (2.66–3.64) and 3.42 (1.90–6.16), respectively). Conclusion: In a sample of urban ophthalmic adult patients, depressive symptoms were highly associated with low vision, smoking, and diabetes. This information can be used to target interventions to those at greatest risk of depressive symptoms.

Patent issues and future trends in drug development

10.5912/jcb42 ◽  
1969 ◽  
Vol 9 (4) ◽  
Author(s):  
Faiz Kermani ◽  
Pietro Bonacossa
Keyword(s):  
Drug Development ◽  
Development Process ◽  
Trade Agreements ◽  
Pharmaceutical Companies ◽  
Future Trends ◽  
Patient Access ◽  
Market Exclusivity ◽  
Political Issues ◽  
International Trade Agreements ◽  
Industrial Sectors

The global biopharmaceutical industry has been one of the most productive and profitable industrial sectors; however, the drug development process remains risky and expensive, with no guarantees of success. The industry believes that a system for the effective intellectual property protection is key to its ability to maintain innovation for drug development. But some critics think that the market exclusivity offered by patents simply allows companies to maximise profits without benefiting patients.Social issues such as patient access to new AIDS treatments and political issues such as international trade agreements mean that the manner in which pharmaceutical companies operate at a business level is becoming subject to closer scrutiny.

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