Unwitting Accomplices: Endocrine Disruptors Confounding Clinical Care.

Burgeoning evidence over the last 25 years has identified myriad synthetic chemicals with the capacity to alter various aspects of hormone synthesis and action. These endocrine-disrupting chemicals (EDCs) have been linked to various diseases, including reproductive disorders, metabolic diseases, and developmental abnormalities, among others. Exposure to EDCs arises from industrial activity, use of personal and home care products, and consumption of contaminated food and water; however, the role of healthcare in exposing individuals to EDCs is grossly underappreciated. Indeed, through the use of medications as well as medical equipment and devices, healthcare providers are unknowing mediators of exposure to EDCs, chemicals that might not only promote disease but that may also antagonize the efficacy of treatments. The ethical implications of provider-dependent exposure are profound. A failure to disclose the endocrine-disrupting properties of medical interventions violates core principles of nonmaleficence, patient autonomy, and justice as well as the practice of informed consent. Furthermore, physicians' lack of knowledge regarding EDCs in medical practice artificially skews risk-benefit calculations that are fundamental to informed medical decision-making. To combat this underappreciated ethical challenge, urgent action is required. Healthcare providers must be educated about endocrine disruption. Known EDCs, defined by endocrinologists, should be clearly labeled on all medical products, and all medication components and devices should be screened for endocrine-disrupting properties. Finally, communication strategies must be devised to empower patients with knowledge about these risks. Providing ethically competent care requires an open acknowledgment of endocrine risks imposed by the medical community that have heretofore been ignored.

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.

Amoxicillin Quality and Selling Practices in Urban Pharmacies and Drug Stores of Blantyre, Malawi.

This study evaluated a newly developed paper analytical device (PAD) for screening amoxicillin samples in Blantyre urban townships. Covert shoppers attempted to buy amoxicillin from a geographically stratified selection of private pharmacies (N = 22 out of 26) and drug stores (N = 23 out of 103) in the township area. According to the PAD results, all 42 samples obtained by the shoppers contained amoxicillin and none contained suspicious filler materials. Next, the products were assayed using high-performance liquid chromatography. Consistent with the PAD results, all samples contained the correct amount of amoxicillin with no unexpected ingredients. However, one sample was purchased as amoxicillin and contained that ingredient, but was packaged in capsules that are normally used to package ampicillin. Almost every sample failed a simple packaging analysis. Nine in 10 samples were missing their original packaging and/or inserts (52.4% repackaged capsules and 35.7% repackaged blister packs). Only 33.3% of the packages had expiry dates, 16.7% had batch numbers, and 47.6% had the manufacturer's name. Dispensing practices were likewise unsatisfactory. Ninety-five percentage of the sellers sold the amoxicillin without a prescription, even though this medicine is regulated as prescription-only in Malawi. Although the chemical analysis showed that amoxicillin quality was good, our market survey revealed poor adherence to prescription-only medicine dispensing of antibiotics, which threatens antimicrobial stewardship efforts. Furthermore, the wide prevalence of repackaging deprives medicines of important information needed during patient's use, regulatory investigations, and pharmacovigilance reporting.

Ethical and Practical Considerations in Removing Black Box Warnings from Drug Labels.

Boxed warnings-also known as "black box" warnings-can be a powerful tool in communicating drug risks to physicians and patients. The overall number of boxed warnings has grown in recent years as the US Food and Drug Administration (FDA) has approved more drugs on the basis of limited pre-marketing information and as new safety issues for marketed drugs have been identified. Two recent manufacturers' petitions to remove boxed warnings on the drugs rosiglitazone (Avandia) and varenicline (Chantix) have led to divergent FDA decisions and revealed different considerations involved in boxed warning imposition and removal. For ethical and practical reasons, the FDA is justified in applying a higher standard for boxed warning removal than for imposition, as removal of a boxed warning may have unintended effects on physician and patient behavior. However, no guidelines on boxed warning removal currently exist. To promote safe use of approved prescription drugs, the FDA should adopt a uniform and transparent process governing decisions to impose or remove boxed warnings.

Moral responsibility to attain thorough pediatric drug labeling.

Many drugs used in children have not been labeled for pediatric use. While this was the standard for many years, recent regulations and incentives have improved the depth and breadth of pediatric drug labeling. Nonetheless, common pediatric drugs have not been adequately labeled, particularly generic and orphaned drugs and drugs that were approved for one age group but never tested in other age groups. Anesthesiologists have a moral responsibility to encourage government, pharmaceutical companies, and researchers to study drugs in children.

[Off-label use in child and adolescent psychiatry. An ongoing ethical, medical and legal problem]. / Off-Label-Use von Psychopharmaka in der Kinder- und Jugendpsychiatrie. Ein andauerndes ethisches, medizinisches und rechtliches Problem.

Off-label use is an ongoing problem in child and adolescent psychiatry. Except methylphenidate and atomoxetine for attention-deficit/hyperactivity disorder (ADHD), most substances used to treat children and adolescents with psychiatric disorders are prescribed off-label. In additional to aspects of drug safety and efficacy the widespread off-label use raises issues of liability in the case of adverse events. In Germany off-label use also poses problems of reimbursement by the health insurance. In the future we expect, driven by written request of the FDA, numerous new indications for novel antipsychotics in the USA for the treatment of so-called childhood bipolar disorders. Given another diagnostic framework in context in Europe, these so-called bipolar disorders in children are very rarely diagnosed. Anyhow, antipsychotics are widely used in the USA and in Europe to treat impulsivity or aggressiveness in children and adolescents. There is still a lack of European labelling of novel antipsychotics for the treatment of schizophrenia. In clinical practice given the risk of liability and other forensic issues in the treatment of schizophrenic patients, this is still one of the major hindrances in the treatment of young schizophrenic patients in Europe. Whereas these drugs may urgently be needed for treatment of psychotic disorders and of impulsivity or aggressiveness, the indication of bipolar as used in the USA leads to a misconception and does not increase availability of licensed modern antipsychotics for minors.

Promotional literature: how do we critically appraise?

There has been a tremendous increase in the number of new and generic drugs coming into the market. The busy practitioner obtains the information from various sources, of which promotional literature forms an important source. The promotional literature provided by the pharmaceutical companies cannot be entirely relied upon; moreover, very few physicians are equipped with the skills of critically appraising it. The new drug should be relevant to the clinician's practice in terms of population studied, the disease and the need for new treatment. The methodology of the study should be carefully judged to determine the authenticity of the evidence. The new drug should be preferred over the existing one if it offers clear advantages in terms of safety, tolerability, efficacy and price. Critical appraisal of promotional literature can provide valuable information to the busy physician to practice evidence-based medicine.

Critical evaluation of the claims made by pharmaceutical companies in drug promotional material in Pakistan.

BACKGROUND: In Pakistan, there is no mechanism to monitor the drug promotional campaign by pharmaceutical industry despite the fact that there is enough evidence that irrational pharmacotherapy is increasingly encountered even in the developed countries due to unethical practices of pharmaceutical promotion. Objectives. To audit the drug promotional claims made by the pharmaceutical companies in Pakistan. METHODS: Drug promotional pamphlets and brochures containing claims for the drugs, which were circulated by the pharmaceutical representatives were collected from 122 general practitioners (GPs) from Karachi and Larkana cities of the Sindh Province. The claims were critically analyzed and audited with the help of currently available evidence in the medical literature. RESULTS: 345 distinct advertisements covering 182 drugs from different manufacturers were critically analyzed for information content. Sixty two out of 345 (18%) of the reviewed advertisements were adjudged to be misleading / unjustifiable, which were again classified as, exaggerated (32%), ambiguous (21%), false (26%), and controversial (21%). The primary source of information (approximately 78%) about the newly launched drugs for the GPs was found to be the pharmaceutical representatives followed by hospital doctors (5%) and colleagues (5%). Furthermore, 110 (90%) GPs were of the view that the drug promotion has definitely an influence on their prescribing pattern. CONCLUSIONS: Since GPs in Pakistan rate pharmaceutical companies as their primary source of information regarding drugs, it can be anticipated that inappropriate advertisement claims would lead to irrational prescribing if physicians had no any other information to follow.