Sourcing decision under interconnected risks: an application of mean–variance preferences approach

Supply chains are customarily associated with multiple interconnected risks originated from supply side, demand side, or from the unanticipated background uncertainties faced by a firm. Also, effective functioning of supply chain hinges on sourcing decisions of inputs (raw materials). Therefore, there is a striking need to analyse the risk preference of the decision maker while going for optimal sourcing decision under varying degree of interconnected supply chain risks. This study addresses this issue by analysing the comparative static effects under interconnected supply chain risks for a risk averse decision-maker, manufacturing and selling products in a regulated market under perfect competition. The decision-maker faces not only supply-side risk (due to random input material prices) but also interconnected risks arising out of background risk (setup costs risk) and demand-side risk (output prices risk). With preferences defined over the mean and standard deviation of the uncertain final profit, this study illustrates the effects of the changes in the pairwise correlations between the three above mentioned risks on the optimum input choice of the manufacturer. To contextualise this study, an India-based generic drug manufacturer cum seller has been considered as a case in the parametric example of our model. Adaptation of the mean–variance framework helps obtaining all the results in terms of the relative trade-off between risk and return, with simple yet intuitive interpretations.

Multidisciplinary Provider Insights to Promote Adoption of Bispecific Antibodies to Treat Cancer in the Community

Bispecific antibodies (BsAbs) are an emerging class of novel immunotherapy agents that have led to major breakthroughs in the treatment of hematologic malignancies. By targeting two separate antigens at the same time, BsAbs can bridge tumor cells to cytotoxic immune cells and bypass several limitations of conventional monoclonal antibody treatment (Wang et al., 2019). In 2020, the Association of Community Cancer Centers (ACCC) launched an ongoing education program to identify and address barriers to awareness, preparedness, adoption, and use of BsAbs to treat cancer. As part of this program, ACCC developed a survey with an expert Advisory Committee to gain an understanding of multidisciplinary cancer providers' experiences with BsAbs. The survey primarily assessed experiences with blinatumomab, the first FDA-approved bispecific antibody for the treatment of malignancy (Newman & Benani, 2016). One hundred and twenty-nine individuals responded to the survey. Sixty percent of these respondents reported prescribing, dispensing, and administering blinatumomab and/or caring for patients being treated with blinatumomab. Of those respondents, 44% were medical oncologists/hematologists, 8% were advanced practice providers (APPs), 17% were nurses, 23% were pharmacists, and 9% fell into an 'Other' category of various other disciplines. Interestingly, the provider experience with blinatumomab varied greatly. Ninety-two percent of oncologists indicated having experience with blinatumomab while only 35% of nurses reported so. Regarding how blinatumomab is used in the community, respondents indicated that 59% of their institutions use it to treat relapsed or refractory acute lymphoblastic leukemia (ALL) while 41% use it to treat ALL with MRD positivity. Additionally, 74% of oncologists use blinatumomab before CAR-T therapy when considering both therapies for patients with ALL. Survey results also showed that although 79% of providers felt comfortable caring for patients being treated with blinatumomab, 59% identified barriers when caring for these patients. Some of the common challenges include transitioning patients from the inpatient to outpatient setting (41%), managing patients in remote areas (33%), securing insurance coverage (28%), managing side effects (27%), assisting patients with costs (24%), and lacking in-house expertise with the drug (22%). Another reported obstacle was the management neurotoxicity and cytokine release syndrome (CRS). In the survey, less than half of oncologists reported experience with managing neurotoxicity or CRS and only 6-9% of APPs reported the same. In general, more oncologists described feeling comfortable with using blinatumomab compared to APPs or nurses. Notably, 23% of nurses did not feel they had all the information needed to safely administer blinatumomab. In terms of opportunities to promote smooth adoption of blinatumomab, 86% of respondents indicated that written guidelines, best practices, and care recommendations would be helpful when caring for patients. Specific desired resources include a list of home health pharmacies and agencies familiar with the drug, care coordinators or navigators, best practices on transitioning from inpatient to outpatient administration, information on how to address problems that may occur with outpatient administration, and in-house or onsite expertise from either the drug manufacturer or someone within the organization. Respondents noted direct patient education as another significant area of need. Eighty-two percent felt that educational resources for patients and caregivers on transitioning from inpatient to outpatient care would be beneficial, and 70% thought that peer support services for patients would also be helpful. Multiple BsAbs are in various stages of development for hematologic malignancies. Using blinatumomab as an example, this survey highlighted challenges to the use of BsAbs and identified opportunities to overcome these obstacles. Translation of best practices for use in the community must be established to reach all eligible patients with cancer who may benefit from these therapies. With this survey data, ACCC is positioned to offer this support. Through its education program, ACCC will build on the survey results to develop content and resources that prepare multidisciplinary providers to welcome BsAbs into the community to treat cancer. Disclosures Atembina: Amgen: Research Funding. Boehmer: Pfizer, Inc: Other: paid consultant within the past 12 months; Amgen: Research Funding. Terrell: Amgen: Honoraria. Koka: Amgen: Honoraria. Janakiram: Amgen: Honoraria. Grothey: Amgen: Honoraria. Morris: Amgen: Honoraria. Rogers: Coherus BioSciences: Speakers Bureau; Astra Zeneca: Speakers Bureau. Kelly: Amgen: Honoraria. Berdeja: Poseida: Research Funding; Acetylon: Research Funding; Lilly: Research Funding; Kite Pharma: Consultancy; Genentech: Research Funding; CRISPR Therapeutics: Consultancy, Research Funding; Celularity: Research Funding; Celgene: Consultancy, Research Funding; Teva: Research Funding; EMD Serono: Research Funding; GlaxoSmithKline: Research Funding; SecuraBio: Consultancy; Legend Biotech: Consultancy; Janssen: Consultancy, Research Funding; Novartis: Research Funding; Incyte: Research Funding; Ichnos Sciences: Research Funding; Abbvie: Research Funding; Amgen: Research Funding; Astex Pharmaceuticals: Research Funding; Bluebird bio: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Takeda: Consultancy; Sanofi: Research Funding. El Chaer: Amgen: Honoraria, Research Funding.

Regulatory restrictions on the use of valproate in girls and women of childbearing potential: status update

In 2019, some restrictions for use of valproic acid in women with reproductive potential by regulatory authorities and the original drug manufacturer based on the results of studies in real clinical practice were introduced. During 2019–2021, there were a further clinical data accumulation and labeling changes. The review presents a critical analysis of the changes in prescribing information and product label. There is a long lead time from the moment when safety data become known to the moment when changes are made to the medicinal product label and patient brochures. Some of the changes, including the need for high doses of folic acid to prevent neural tube defects, are debatable. Repealing the provision for mandatory archiving of informed consent forms for valproic acid use in girls and women raises legal risks. Improvements in pregnancy prevention programs and further research on the safety of valproic acid in real-world clinical settings are needed.

Alternate dosage formulations of oral targeted anticancer agents

Objective Oral anticancer therapies have demonstrated superior outcomes compared to traditional cytotoxic chemotherapy in many disease states. However, certain patients may not be candidates for these agents due to odynphagia or dysphagia. The purpose of this review is to summarize the data for extemporaneous compounding of oral anticancer agents. Data sources Food and drug administration approvals of oncology agents were reviewed to identify oral anticancer therapies. In order to find alternative administration options: the package inserts of each of these agents were reviewed, each medication was searched in a tertiary drug information resource, the medical information teams of each drug manufacturer were contacted to inquire about proprietary data, sites with pediatric trials were contacted, a primary literature search was performed, and listservs for national pharmacy and oncology organizations were reviewed. Data summary Eighty-five food and drug administration-approved oral anticancer therapies were identified to be included. Of those agents, nine (11%), had information in the package insert related to alternative administration. After further research, 46 (54%) of the agents had some information related to alternate formulations for administration. The recipes and stability of each of these compounds is included. Conclusions The majority of agents do not have Phase I or II trials that assess safety or pharmacokinetics of alternative formulations. Clinicians should exercise caution when recommending or administering these agents outside of food and drug administration-approved indicated use and utilize clinical judgment in assessing the risks and benefits of altering anticancer compounds. However, the alternative administration considerations presented can increase access to oncology patients who have difficulty swallowing.

Associated mood changes with naloxegol therapy for opioid-induced constipation in a patient with psychiatric disease

The objective of this clinical case report is to highlight unusual adverse effects brought on by Naloxegol therapy in a patient with underlying psychiatric illness. The patient is a 68-year-old female, with a psychiatric history of bipolar disorder, who presented for chronic pain management and opioid-induced constipation. After failing other therapies, she was trialed on Naloxegol on three separate occasions. She experienced mood lability with symptoms including agitation, confusion, irritability, hysteria and unprompted crying spells on each occasion. Notably, the drug manufacturer does not describe mood lability, nor the profound psychiatric manifestations outlined in our case report, as side effects of Naloxegol. Clinicians may consider judicious prescription of Naloxegol when treating opioid-induced constipation in patients with pre-existing psychiatric co-morbidities.

СOVID-19 as an Indicator of Customer Value in the Medicine Market

COVID 19 virus has made significant changes in our lives and has led to a total change in the formats of interaction between the consumer and the seller in the pharmaceutical market. Health suddenly became customer value approach the choice of a medicine differently. The classical approach to the formation of consumer value in the drug market is losing its relevance. What really determines consumer value in the pharmaceutical market? What can a drug manufacturer offer in response to a consumer's consumer aspirations? This article reflects the attempts of the authors to determine the parameters of changed consumer behavior within the values of the pharmaceutical market.

The Drug Manufacturer as a Drug Information Resource

Pharmacists use a myriad of drug resources for patient care; however, the drug manufacturer is often overlooked and underutilized as a resource for drug information. Pharmaceutical companies have a medical information department that is responsible for providing drug information to pharmacists and the public about the company’s products. This article will explain the purpose and functions of the medical information department within a pharmaceutical company. In addition, the type of information that may be requested and the ways to request drug information will be discussed.

SIDE EFFECTS OF DIETHYLSTILBESTROL (DES) FROM THE PERSPECTIVE OF TORT LAW

The aim of the article is to analyze the reasoning of the Supreme Court of California in Sindell v. Abbott Laboratories. Materials and methods: Materials of the study encompass US case law as well as case law of other countries concerning compensation of damage caused by defective drugs and other cases of uncertain causation. The survey is conducted within the framework of comparative law studies. In addition, elements of law and economics approach are also employed in the paper. Conclusions: Case of Sindell v. Abbott Laboratories has launched a new direction in discourse on causation in tort law and product liability. The mathematical elegance of the Court's theory is that net burden of liability borne by a particular drug manufacturer is equal to the amount of damage actually caused by its drug.