Industry strategies to market opioids to children and women in the USA: a content analysis of internal industry documents from 1999 to 2017 released in State of Oklahoma v. Purdue Pharma, L.P. et al.

OBJECTIVE: Identify advertising strategies used to market opioids to women and children. DESIGN: Qualitative content analysis of internal pharmaceutical industry documents released in litigation, dated between 1999 and 2017. SETTING: USA. PARTICIPANTS: Opioid manufacturers (Janssen, Ortho-McNeil, Purdue, Teva (Actavis), Janus, Cephalon); women; children. PRIMARY AND SECONDARY OUTCOME MEASURES: Advertising campaigns, industry executive statements regarding marketing goals METHODS: We examined ((DATASET) link: https://www.industrydocuments.ucsf.edu/drug/) documents released in State of Oklahoma v. Johnson & Johnson (2019) to identify marketing strategies and campaigns developed by opioid manufacturers that focused on children and women, as well as public records, including websites developed by manufacturers and their allies, to confirm whether marketing campaigns proposed in internal industry documents were implemented. Documents identified as relevant were coded for themes based on expectations drawn from previous research on marketing using internal industry documents, which included making emotional appeals and understating the risks of addiction. RESULTS: We found that opioid manufacturers sought to recruit coaches and school nurses to encourage opioid use by children, developed unbranded initiatives suggesting adolescents ask providers for pain care medications, suggested that opioid use could reduce health risks associated with untreated pain among women and advocated to policy makers that women faced unmet needs for pain medication. CONCLUSIONS: The USA strictly regulates direct marketing of medications but does not place the same restrictions on indirect marketing and unbranded campaigns, which encourage people to seek treatment without indicating the names of specific products. Opioid manufacturers in the early 21st century appear to have relied largely on unbranded campaigns for marketing, which they described externally as public health promotion and internally as a way to increase sales of opioids. The rapid increase in opioid use concomitant with these campaigns suggests that additional scrutiny of this kind of marketing may be needed in order to protect vulnerable groups.

Marketing Opioids to Veterans and Older Adults: A Content Analysis of Internal Industry Documents Released from State of Oklahoma v. Purdue Pharma LP, et al.

CONTEXT: From 1999 to 2018 the opioid epidemic claimed more than 500,000 lives in the United States. Military veterans and older adults were particularly affected; veterans' deaths attributed to opioid use increased by 65% from 2010 to 2016, while opioid prescriptions for older adults increased ninefold between 1995 and 2010. METHODS: We reviewed internal pharmaceutical industry documents released in legal discovery to determine how companies targeted these groups to increase prescribing and sales. This review included an analysis of corporate goals and plans identified through internal emails, sales pitches, and presentations. FINDINGS: These policy and advertising campaigns focused on (a) lobbying policy makers, (b) undertaking unbranded campaigns promoting opioid use, and (c) promoting opioid use in research and the popular media. Opioid manufacturers claimed that opioids could resolve preexisting concerns identified among military veterans and older adults and that the use of opioids would improve quality of life. These campaigns were positioned as public health initiatives and efforts to increase disease awareness. CONCLUSIONS: The findings suggest a need for regulatory reform and transparency related to lobbying, advocacy group relationships with industry, and pharmaceutical advertising.

Discovery and Structure-Activity-Relationship Study of N-Alkyl-5-hydroxypyrimidinone Carboxamides as Novel Antitubercular Agents Targeting Decaprenylphosphoryl-ß-d-ribose 2'-Oxidase.

Magnesium plays an important role in infection with Mycobacterium tuberculosis ( Mtb) as a signal of the extracellular environment, as a cofactor for many enzymes, and as a structural element in important macromolecules. Raltegravir, an antiretroviral drug that inhibits HIV-1 integrase is known to derive its potency from selective sequestration of active-site magnesium ions in addition to binding to a hydrophobic pocket. In order to determine if essential Mtb-related phosphoryl transfers could be disrupted in a similar manner, a directed screen of known molecules with integrase inhibitor-like pharmacophores ( N-alkyl-5-hydroxypyrimidinone carboxamides) was performed. Initial hits afforded compounds with low-micromolar potency against Mtb, acceptable cytotoxicity and PK characteristics, and robust SAR. Elucidation of the target of these compounds revealed that they lacked magnesium dependence and instead disappointingly inhibited a known promiscuous target in Mtb, decaprenylphosphoryl-ß-d-ribose 2'-oxidase (DprE1, Rv3790).