Claims Of Safety Research Articles

The marketing of OxyContin®: A cautionary tale.

This paper provides a review of Purdue Pharma, LP's development and marketing of the long-acting oral narcotic OxyContin®. Within five years of the drug's launch, OxyContin® became the number-one prescribed Schedule II narcotic in the United States. This commercial success was in part the result of a marketing campaign that promoted questionably "distinctive" benefits and minimised the very real dangers of OxyContin®, which include abuse, addiction, overdose, and death. The marketing was based on scientifically invalid or unproven claims of safety and efficacy, inappropriate, off-label marketing, and inadequate warnings. When the FDA belatedly asked for changes to some of the marketing language, Purdue exploited these changes to further marketing objectives and misled healthcare practitioners. This case highlights questions of industry and governmental/regulatory accountability and responsibility for the production, marketing and sale of pharmaceutical products that increase risk while driving enhanced profits.

Extracts of Moringa oleifera lack cytotoxicity and attenuate oleic acid-induced steatosis in an in vitro HepG2 model

Moringa oleifera Lam. has received much praise over its potential benefits to health and nutrition, however, not much literature is available to support claims of hepatic safety. The liver, as primary xenobiotic metaboliser, is subject to high levels of cytotoxicity. As such, hepatotoxicity has been a consistent hurdle during the drug discovery and development process. The aim of this study was to assess the in vitro hepatotoxic properties of both hot water and methanol extracts of M. oleifera leaves by assessing common mechanisms of cytotoxicity in the HepG2 cell line. Also, the ability of these extracts to protect against in vitro oleic acid-induced steatosis was investigated.Tentative phytochemical profiling was done by ultra-performance liquid chromatography coupled to a photodiode array detector and high-definition mass spectrometer. In vitro cytotoxicity was assessed by sulforhodamine B staining (cell density), dihydro-dichlorofluorescein diacetate cleavage (reactive oxygen species), monochlorobimane adduct formation (reduced glutathione), JC-1 ratiometry (mitochondrial membrane potential), nile red staining (fatty acids), Ac-DEVD-AMC cleavage (caspase-3/7 activity), thiobarbituric acid reactive species production (lipid peroxidation), chemiluminescence (adenosine triphosphate; ATP), propidium iodide distribution (cell cycle) and Annexin V-FITC dual staining (mode of cell death). The protective action of the extracts was determined using an oleic acid-induced model of steatosis.Phytochemical profiling tentatively identified several chemicals within the extracts. Viability assessment indicated slight cytotoxicity at 100 μg/mL after both the hot water and methanol extract exposure (approximately 8–14%), however, this was not reflected by cell density results. The cell cycle remained unperturbed, apart from a slight increase in G0/G1-phase. Although mitochondrial depolarisation was evident, especially after exposure to the methanol extract, it did not translate to cytotoxicity in the form of oxidative stress. Reactive oxygen species generation was only observed at 100 μg/mL hot water extract exposure (1.99-fold), with the rest of the values being below baseline. Slight lipid peroxidation (1.48-fold at 100 μg/mL) was observed after methanol extract exposure. The GSH was unaltered. Fatty acid levels reduced, especially after methanol extract exposure (0.43-fold at 100 μg/mL), which may be indicative of increased mitochondrial respiration. Caspase-3/7 activity and ATP were decreased slightly. Methanol extracts were particularly active in protecting cells from oleic acid-induced cytotoxicity and fatty acid accumulation, with a decrease of up to 27% and 4.1-fold at 3.2 μg/mL, respectively.Although the in vitro results suggest hepatic safety, further investigation is needed to ascertain the underlying mechanisms of cytotoxicity at concentrations above 100 μg/mL, particularly the effects on mitochondrial membrane stability. Although mitochondrial membranes were depolarised, this may assist with the reduction of fatty acid levels and offer protection against oleic acid-induced steatosis.

Labeling food safety attributes: to inform or not to inform?

We examine the impact of food labels that make unsupported claims of food safety and labels that provide information to support such claims on consumer choices and examine consumers’ willingness to pay for beef products with these different food safety labeling cues. Empirical results from a survey of grocery shoppers in a Midwestern city in the USA show that more than two thirds of respondents who received a label with unsubstantiated food safety claims chose this option and were willing to pay the highest price premium for it, compared to the less preferred labeling options that provided information to support food safety claims.

Rebutting Drs. DeStefano and Offit's claims of vaccine safety in: Principal Controversies in Vaccine Safety in the United States

Rebutting Drs. DeStefano and Offit's claims of vaccine safety in: Principal Controversies in Vaccine Safety in the United States

Fake Medical News: The Ethics and Dangers of Health Product Advertising Disguised as Real News

Leading national newspapers in the US, challenged financially by the transition from paper to electronic media, are allowing drug and medical product advertisers to format their advertisements to appear like actual, authentic news articles. This news mimicry is intended to deceive consumers, and often makes claims of clinical efficacy and safety that are not evidence based and substantiated. An example of such an advertisement is presented and the clinical implications are considered, including recommendations to public health leadership organizations.

Chicken Egg Yolk Antibodies (IgY) for Prophylaxis and Treatment of Rotavirus Diarrhea in Human and Animal Neonates: A Concise Review.

The rotavirus-induced diarrhea of human and animal neonates is a major public health concern worldwide. Until recently, no effective therapy is available to specifically inactivate the rotavirion particles within the gut. Passive immunotherapy by oral administration of chicken egg yolk antibody (IgY) has emerged of late as a fresh alternative strategy to control infectious diseases of the alimentary tract and has been applied in the treatment of diarrhea due to rotavirus infection. The purpose of this concise review is to evaluate evidence on the properties and performance of anti-rotavirus immunoglobulin Y (IgY) for prevention and treatment of rotavirus diarrhea in human and animal neonates. A survey of relevant anti-rotavirus IgY basic studies and clinical trials among neonatal animals (since 1994-2015) and humans (since 1982-2015) have been reviewed and briefly summarized. Our analysis of a number of rotavirus investigations involving animal and human clinical trials revealed that anti-rotavirus IgY significantly reduced the severity of clinical manifestation of diarrhea among IgY-treated subjects relative to a corresponding control or placebo group. The accumulated information as a whole depicts oral IgY to be a safe and efficacious option for treatment of rotavirus diarrhea in neonates. There is however a clear need for more randomized, placebo controlled and double-blind trials with bigger sample size to further solidify and confirm claims of efficacy and safety in controlling diarrhea caused by rotavirus infection especially among human infants with health issues such as low birth weights or compromised immunity in whom it is most needed.

Medicines Regulatory Harmonization: International Collaboration as a Key to Improve Public Health

Over the past 30 years, many national drug regulatory authorities have embarked on a process of gradual harmonization of all the technical aspects of studies, processes, and tests that generate the data necessary to support claims of quality, safety, and efficacy of medicines. This has been mainly a trade-driven process characterized by “region-specific” harmonization initiatives; the less-resourced authorities started this processes much later than the better-resourced ones. The immediate outcome of harmonized requirements is the eliminating of country-specific tests and studies, and the narrowing of gaps in the interpretation of data. This reduced the costs for pharmaceutical companies by enabling them to develop one single set of data and documentation to be submitted to several different countries. In addition, the harmonization processes are beneficial for public health: open-minded technical discussions and the exchange of ideas and experience among regulators of different countries contributes to strengthening the capacity of national authorities to expedite the assessment of priority medicines, and to filter out unsafe or substandard products.

Letter: interruption of beta‐blockers in patients with cirrhosis – hasten slowly!

Payancé et al.'s conclusion ‘interruption of beta-blockers in patients with cirrhosis may not require particular dosing or surveillance’ is a slippery slope.1 Indeed, findings should have been more robust. First, this prospective clinical trial was restricted to patients with cirrhosis undergoing right heart catheterisation, this means patients hospitalised, probably also receiving premedication or at least reassurance, and resting quietly at the time of the investigation. In such instances without stressful events causing adrenergic discharge, it is unlikely to observe consequences of receptors’ upregulation. Similarly, rebound propranolol withdrawal reaction was not obvious in patients with angina pectoris having propranolol abruptly discontinued prior to elective coronary arteriography.2 Rebound events after withdrawal of beta blockade are related to the specific clinical setting and easily observed by measuring heart rate under simple conditions of increased sympathetic drive - such as standing or the Valsalva manoeuvure.3 Second, the lack of rebound after withdrawal may also be due to the lack of effective beta-adrenergic blockade (inadequate dosage or poor compliance). Third, claims of safety need a real-life setting during a longer period of time in a larger series. Last, the concern for safety should have not been restricted to gastro-intestinal bleeding considering these 25 patients with probably specific risk factors for coronary artery disease.4 Indeed, the test is far from routine and is only considered when there are relevant risk factors among transplantation candidates.5, 6 Could Payancé et al. provide the risk factors of the 25 patients justifying the myocardial stress testing vs. the others groups? Despite being 40 years old, the advice ‘chronically administered propranolol should be gradually reduced, and activity restricted during its withdrawal’ is still topical.4, 5 Declaration of personal and funding interests: None.

Geographical Indications, Food Safety, and Sustainability Challenges and Opportunities

This paper examines the legal and policy relationship reinforcement amongst international standards for GIs, food safety standards, and other claims of quality or safety. The paper addresses those relationships within the context of international trade agreements protecting GIs, such as the 1994 TRIPS Agreement, the EU-Canada Comprehensive Economic and Trade Agreement (CETA), and the chapter on intellectual property and geographical indications in the Transatlantic Trade and Investment Partnership (TTIP) currently under negotiation. Trade agreements also discipline food safety measures and non-GI indications of quality or safety such as “organic” and “GMO-free.” Accordingly, the paper also considers the extent to which international trade agreements such as the WTO Agreements on the Application of Sanitary and Phytosanitary Standards (SPS Agreement) and Technical Barriers to Trade (TBT) might interact with the analysis.

Healing Rate and Autoimmune Safety of Full-Thickness Wounds Treated With Fish Skin Acellular Dermal Matrix Versus Porcine Small-Intestine Submucosa

A novel product, the fish skin acellular dermal matrix (ADM) has recently been introduced into the family of biological materials for the treatment of wounds. Hitherto, these products have been produced from the organs of livestock. A noninferiority test was used to compare the effect of fish skin ADM against porcine small-intestine submucosa extracellular matrix in the healing of 162 full-thickness 4-mm wounds on the forearm of 81 volunteers. The fish skin product was noninferior at the primary end point, healing at 28 days. Furthermore, the wounds treated with fish skin acellular matrix healed significantly faster. These results might give the fish skin ADM an advantage because of its environmental neutrality when compared with livestock-derived products. The study results on these acute full-thickness wounds might apply for diabetic foot ulcers and other chronic full-thickness wounds, and the shorter healing time for the fish skin-treated group could influence treatment decisions. To test the autoimmune reactivity of the fish skin, the participants were tested with the following ELISA (enzyme-linked immunosorbent assay) tests: RF, ANA, ENA, anti ds-DNA, ANCA, anti-CCP, and anticollagen I and II. These showed no reactivity. The results demonstrate the claims of safety and efficacy of fish skin ADM for wound care.

No scientific consensus on GMO safety

A broad community of independent scientific researchers and scholars challenges recent claims of a consensus over the safety of genetically modified organisms (GMOs). In the following joint statement, the claimed consensus is shown to be an artificial construct that has been falsely perpetuated through diverse fora. Irrespective of contradictory evidence in the refereed literature, as documented below, the claim that there is now a consensus on the safety of GMOs continues to be widely and often uncritically aired. For decades, the safety of GMOs has been a hotly controversial topic that has been much debated around the world. Published results are contradictory, in part due to the range of different research methods employed, an inadequacy of available procedures, and differences in the analysis and interpretation of data. Such a lack of consensus on safety is also evidenced by the agreement of policymakers from over 160 countries - in the UN’s Cartagena Biosafety Protocol and the Guidelines of the Codex Alimentarius - to authorize careful case-by-case assessment of each GMO by national authorities to determine whether the particular construct satisfies the national criteria for ‘safe’. Rigorous assessment of GMO safety has been hampered by the lack of funding independent of proprietary interests. Research for the public good has been further constrained by property rights issues, and by denial of access to research material for researchers unwilling to sign contractual agreements with the developers, which confer unacceptable control over publication to the proprietary interests. The joint statement developed and signed by over 300 independent researchers, and reproduced and published below, does not assert that GMOs are unsafe or safe. Rather, the statement concludes that the scarcity and contradictory nature of the scientific evidence published to date prevents conclusive claims of safety, or of lack of safety, of GMOs. Claims of consensus on the safety of GMOs are not supported by an objective analysis of the refereed literature.

Pharmacological, Microbiological and Clinical Activity of Feminine Intimate Cleansers Based on Plant Extracts Active Principles (Saugella Line)

Introduction: The use in intimate hygiene of active substances plays an important role in maintaining the balance of the vaginal ecosystem. The most medically based cleansers are promoted to doctors through a classic medical information, even if classified as cosmetics. The present paper assessed the reliability of the pharmacological, microbiological and clinical claims both on the active principles of Salvia officinalis, Thymus vulgaris, Camomilla recutita and Calendula officinalis extracts, contained in the most used hygiene product line. Methods: The experimental activity was studied on the inhibition of microbes’ adhesion to human vaginal epithelial cells, morphostructural damages to germ cells, inhibition of microbial biofilms, and anti-inflammatory tests. The clinical data were collected according to the use recommendation as daily intimate cleanser, uid or bid for four weeks: salvia (SD - Saugella Dermoliquido) in fertile age women, thymus (SA – S. Attiva) in pregnancy, breastfeeding and risk of vulvovaginal infection, chamomile (SP – S. Poligyn) in postmenopausal women, calendula (SG – S. Girl) in pre-adolescent girls prone to vaginal irritations. At baseline and after 4-week treatment, vaginal pH, signs/symptoms, and sexual activity were evaluated. Results: The experimental data showed the antibacterial, antimycotic, anti-inflammatory and antioxidant activity of the natural principles contained in the four extracts. The clinical studies evidenced the significant reduction of genital signs and symptoms (itching, burning, erythema, edema, vaginal dryness, dyspareunia) and the improvement of sexual female disorder. Conclusions: Correct intimate hygiene improves quality of woman’s life and can prevent minor vulvo-vaginal pathologies. The cleanser selection should be tailored on the age and physiopathological condition of the woman. The claims of efficacy and safety that supports the recommendation of the use in daily practice of the Saugella line products containing Salvia, Thymus, Chamomile, and Calendula extracts are consistent and reliable.

Qualitative analysis of transgender inmates' correspondence: implications for departments of correction.

Claims of inadequate health care and safety afforded to transgender inmates have become the subject of litigation. This article reviews 129 unsolicited letters from transgender inmates writing from 24 states and the Federal Bureau of Prisons to identify their concerns. Among the letters reviewed were reports from 10 inmates who had filed lawsuits naming departments of correction (DOCs) as defendants, claiming inadequate access to transgender health care. Five of these lawsuits have gone to trial. In all of those cases, the defendant settled the matter or was found liable as of the time of this report. Claims of inadequate care for transgendered patients that have sufficient merit to be fully litigated in U.S. courts appear likely to produce verdicts in favor of plaintiff inmates. The information gleaned from reviewing letters from transgendered inmates may alert staffs of DOCs to concerns worth addressing proactively to avoid the costs associated with transgender-related lawsuits.

Unregulated Promotion and Sale of Herbal Remedies: A Safety and Efficacy Evaluation of Twelve Such Commercial Products Claimed to be Beneficial and Patronised for a Variety of Ailments in Nigeria

Preparation, distribution, advertisement, and usage of phythomedicinal products in Nigeria are weakly regulated raising genuine concern for public safety. In this study, twelve highly patronised commercial herbal products (S1- S12) claimed to be beneficial in the management of either diabetes mellitus, diarrhoea, or hypertension were procured from herbal vendors in Nigeria and evaluated against their claims of efficacy and safety using established whole animal and in vitro models. S1, S2, and S3 were tested for anti-hyperglycaemic activity in normoglycemic and diabetic rats and only S1 and S2 showed some reductions in blood glucose at some time points but S3 produced no reduction in blood sugar at all the time points. Three samples, S4, S5, and S6 significantly (P ≤ 0.05) inhibited the frequency of diarrhoea drops in rats at a dose of 250 mg/kg and caused minimal (P>0.05) reduction in intestinal transit of a charcoal meal in mice. Infusion of aqueous extract of samples (S7-S12) up to 1mg/kg, showed that only the mean arterial blood pressure of cannulated cat was reduced by S7 and S8 but samples S9, S10, S11, and S12 did not cause any reduction in the arterial blood pressure. At a dose of 1 mg/kg, S7 and S8 caused a BP reduction of 150 and 76.92% relative to the reduction produced by ACh (1 μg/kg). The safety of these samples was assessed by determining the acute toxicity of these preparations and checking the nature of contaminating organisms and the levels of such contamination (bio-load). Acute toxicity studies in mice showed that at doses above 5000 mg/kg, per os, all the herbal samples did not cause death or produced signs of acute intoxication in mice. The samples were found to be contaminated with a variety of microorganisms, although their bio-loads were largely within pharmacopoeia specification. S7 is the most heavily contaminated; S3, S4, and S12 are contaminated with Gram negative organisms that may be potentially pathogenic. The outcome of this preliminary investigations demonstrates the need for stricter regulation and registration of commercial herbal products. Post-marketing surveillance, pharmacovigilance, and random screening of herbal products should be entrenched in the regulatory framework to quickly dictate any possible adverse effect and ensure consistency in the quality of distributed herbal medicines.

Safety and Long Term Outcomes with High Flow Nasal Cannula Therapy in Neonatology: A Large Retrospective Cohort Study.

High flow nasal cannula therapy (HFT) has been shown to be similar to nasal continuous positive airway pressure (nCPAP) in neonates with respect to avoiding intubation. The objective of the current study is to determine if there are trends for adverse safety and long-term respiratory outcomes in very low birth weight infants (<1500 g) from centers using HFT as their primary mode of non-invasive respiratory support compared to data from the largest neonatal outcomes database (Vermont Oxford Network; VON). A multicenter, retrospective analysis of pulmonary outcomes data was performed for the calendar years 2009, 2010 and 2011. Performance of five HFT centers was compared with population outcomes from the VON database. The five HFT centers routinely use flow rates between 4-8 L/min as described by the mechanistic literature. Weighted average percentages from the five HFT centers were calculated, along with the 95% confidence intervals (CI) to allow for comparison to the VON means. Patient characteristics between the HFT centers and the VON were not different in any meaningful way, despite the HFT having a greater percentage of smaller infants. The average VON center primarily used nCPAP (69% of all infants) whereas the HFT centers primarily used HFT (73%). A lesser percentage of VLBW infants in the HFT cohort experienced mortality and nosocomial infection. Compared to VON data, an appreciably lesser percent of the HFT cohort were receiving oxygen at 36 weeks and less went home on oxygen. Considering there was no trend for adverse events, and there was a trend for better outcomes pertaining to long-term oxygen use, these data support claims of safety for HFT as a routine respiratory management strategy in the NICU.

Media, fear, and nuclear energy: A case study

Although electricity generation technologies and safety have improved gradually over time, nuclear power, including generation facilities and waste repositories, are seemingly stigmatized in American culture. Contemporary literature has considered the impact of widely broadcasting nuclear accidents and how media coverage might alter public risk perceptions and in turn, U.S. nuclear policy. This paper discusses the vacillation of public support in recent decades and its ties to both media and scientific reporting. The analysis identifies how media coverage of accidents at Chernobyl, Three-Mile Island, and Fukushima overwhelmed scientific claims of safety and security in nuclear energy production. Additionally, the discussion considers how to bridge the information gap between scientists, citizens, and policymakers through increased knowledge dissemination. Finally, the implications of improved scientific communication in democratic policymaking processes are discussed.

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The Detection of Adverse Events in Randomized Clinical Trials: Can we Really Say New Medicines are Safe?

While it is well known that randomized controlled trials (RCTs) are usually designed with sufficient sample size and power to detect the efficacy but not safety of a medicine, the extent to which RCTs quantify safety has not been well ascertained. The aim of this study was to assess the safety data available for five commonly prescribed medicines at the time of marketing. Published RCTs for five medicines risperidone, sertraline, donepezil, strontium ranelate and tramadol extended release were identified. All adverse events (AEs) in the trials were independently extracted by two clinical researchers. Using the sample size in the trials, the power to detect the observed difference in AEs rates between the treatment and placebo groups was calculated. A power of 80% or more was deemed adequate to detect AEs; studies with power of < 80% were deemed insufficiently powered to detect AEs. 12 RCTs were identified. Six trials were insufficiently powered to detect any of the potential AEs reported. Of the 150 evaluated AEs, the trials were insufficiently powered to detect 81% (122/150) of the AEs reported. For the adverse events that were detected with adequate powered clinical trials, only 53% (10/19) of potentially very common AEs (≥10%) and 17% (18/106) of potentially common AEs (1%-<10%) were identified. Trials are insufficiently powered to detect the majority of adverse events that are reported in clinical trials, even for common adverse events. Observations other than primary efficacy endpoints such as AEs that are not prespecified with adequate power should be treated as hypothesis generating only and not justification of evidence. Claims of safety based on trial evidence not designed for the safety endpoint are often premature.

FDA Actions Against Health Economic Promotions, 2002–2011

ObjectiveTo investigate Food and Drug Administration (FDA) regulatory actions against drug companies' health economic promotions from 2002 through 2011 to understand how frequently and in what circumstances the agency has considered such promotions false or misleading. MethodsWe reviewed all warning letters and notices of violation (“untitled letters”) issued by the FDA's Division of Drug Marketing, Advertising and Communications (DDMAC) to pharmaceutical companies from January 2002 through December 2011. We analyzed letters containing a violation related to “health economic promotion,” defined according to one of several categories (e.g., implied claims of cost savings due to work productivity or economic claims containing unsupported statements about effectiveness or safety). We also collected information on factors such as the indication and type of media involved and whether the letter referenced Section 114 of the Food and Drug Administration Modernization Act. ResultsOf 291 DDMAC letters sent to pharmaceutical companies during the study period, 35 (12%) cited a health economic violation. The most common type of violation cited was an implied claim of cost savings due to work productivity or functioning (found in 20 letters) and economic claims containing unsubstantiated comparative claims of effectiveness, safety, or interchangeability (7 letters). The violations covered various indications, mostly commonly psychiatric disorders (6 letters) and pain (6 letters). No DDMAC letter pertained to Food and Drug Administration Modernization Act Section 114. ConclusionThe FDA has cited inappropriate health economic promotions in roughly 12% of the letters issued by the DDMAC. The letters highlight drug companies' interest in promoting the value of their products and the FDA's concerns in certain cases about the lack of supporting evidence.

Maths for medications: an analytical exemplar of the social organization of nurses' knowledge

Within the literature that circulates in the discourses organizing nursing education, there are embedded assumptions that link student performance on maths examinations to safe medication practices. These assumptions are rooted historically. They fundamentally shape educational approaches assumed to support safe practice and protect patients from nursing error. Here, we apply an institutional ethnographic lens to the body of literature that both supports and critiques the emphasis on numeracy skills and medication safety. We use this form of inquiry to open an alternate interrogation of these practices. Our main argument posits that numeracy skills serve as powerful distraction for both students and teachers. We suggest that they operate under specious claims of safety and objectivity. As nurse educators, we are captured by taken-for-granted understandings of practices intended to produce safety. We contend that some of these practices are not congruent with how competency actually unfolds in the everyday world of nursing practice. Ontologically grounded in the materiality of work processes, we suggest there is a serious disjuncture between educators' assessment and evaluation work where it links into broad nursing assumptions about medication work. These underlying assumptions and work processes produce contradictory tensions for students, teachers and nurses in direct practice.