Rethinking counterfeit medical supply chains: A critical review of the current literature.

The medical device and pharmaceutical industries include a range of drugs, machines, instruments, and apparatuses used to prevent, diagnose, treat disease and illness, or aid in rehabilitation for patients, and are expected to grow substantially in the coming years. However, they are often targets of criminal organizations who manufacture and profit from fraudulent products, infiltrating the market with counterfeit medical supply chains. In this paper, we discuss and analyze the extent and nature of this problem and make suggestions for mitigation and prevention of this worldwide challenge. Ultimately, we argue that a holistic approach is essential to addressing this problem, including the creation and dissemination of reliable and good quality data, developing healthcare systems to be more robust, establishing/enhancing intra- and international cooperation around this issue, and employing effective technological solutions, such as digital tracing.

Sales revenues for new therapeutic agents approved by the US Food and Drug Administration from 1995 to 2014: a retrospective study.

OBJECTIVES: To analyze worldwide sales of new therapeutic agents and to estimate the time it takes for product sales to exceed industry-wide average drug development costs. METHODS: Data obtained from company reports were analyzed to track worldwide sales of new medicines approved by the US Food and Drug Administration from 1995 to 2014. All sales figures were reported in 2019 US dollars. Kaplan-Meier curves were used to evaluate the time it took for discounted product sales to exceed the average costs associated with developing one new drug (accounting for the costs of failed trials), using published estimates of these costs. RESULTS: Based on data for 361 of 558 new therapeutic agents approved over the study period (median follow-up: 13.2 years), mean sales revenue per product was $15.2 billion through the end of 2019; the median was $6.7 billion. These products jointly generated global sales of $5.5 trillion since approval. Revenues were highly skewed, with the 25 best selling products (7%, 25/361) accounting for 38% of this amount ($2.1 trillion/$5.5 trillion). About 47% of products had discounted sales that exceeded the estimated industry-wide average costs of development within 5 years of approval, and 75% within 10 years. After attributing potential production, marketing, and other costs, these numbers dropped to 21% of products within 5 years of approval, and 46% within 10 years. CONCLUSIONS: Sales of new medicines approved from 1995 to 2014 were highly skewed, but a majority of products had net discounted sales that exceeded the industry-wide average costs of development within 10 years of approval. An understanding of how sales revenues accrue in the years after initial approval, alongside data on business costs, can inform discussions about how to incentivize private investment in innovation while ensuring affordable prices for patients and the health-care system.

Timeliness of Health Technology Assessments and Price Negotiations for Oncology Drugs in Canada.

Purpose: To evaluate whether time targets for Canadian Agency for Drugs and Technologies in Health (CADTH) reimbursement reviews and pan-Canadian Pharmaceutical Alliance (pCPA) price negotiations are being achieved for oncology drugs. Materials and Methods: Recommendations, dates of submission and publication, and indications for oncology medicines issued between January 2014 and December 2023 were recorded from CADTH's reimbursement reports webpage. The date any negotiation began and the date it was completed (successfully or not), or when a decision was made not to pursue negotiation was extracted from the pCPA's webpage. The duration of each CADTH review and pCPA negotiation was calculated, together with time between CADTH's recommendation and start of the pCPA negotiation or a decision not to negotiate. Percentages of reviews completed within CADTH's target and of times taken by the pCPA to decide whether to negotiate and by its price negotiations completed within the relevant targets were calculated. Results: CADTH achieved its 270-days target in 88.2% to 100% of reviews issued between 2015 and 2019 but only in 65.9% to 73.1% of reviews issued in the last three years of the decade. CADTH's "typical timeline" of 180 days was achieved in under 40% of reviews issued in 2015 and not attained in any review in 2021, 2022 or 2023. The pCPA's target of 60 days for deciding whether to negotiate was achieved for all recommendations issued in 2014 but dropped below 40% for the last seven years of the decade; its target of 130 days for negotiations was achieved for over 85% of the recommendations in 2014 but decreased to only 14.3% in 2016 and then gradually increased to 61.5% in 2023. Conclusion: CADTH's "typical timeline" and the pCPA's targets were not met sufficiently to be meaningful. Their processes take too long for cancer drugs.

Canadian patients and providers are often frustrated and concerned about the timeliness of the country's health technology assessment (HTA) and price negotiation processes, especially for cancer drugs. HTAs are carried out to evaluate the benefit of a medicine in comparison with its cost to see whether the drug is of sufficient value to add it to the benefit lists of government drug plans. HTAs are performed by the Canadian Agency for Drugs and Technologies in Health (CADTH) for all of Canada, except the province of Quebec, and price negotiations with drug developers are carried out by the pan-Canadian Pharmaceutical Alliance (pCPA) on behalf of all government drug plans. We used data from the websites of CADTH and the pCPA on HTA reviews of cancer drugs issued between January 2014 and December 2023 and price negotiations for these drugs to assess whether CADTH and the pCPA complied with their stated target times for completing their processes. We found that CADTH's reviews and the pCPA's price negotiations failed to meet their targets for cancer drugs in the past 10 years and that the timeliness of their performance has, in most cases, deteriorated. HTA and price negotiation processes for cancer drugs take too long in Canada.

Dermatology medications with the highest cost burden on Medicare Part D: Potential implications of the Inflation Reduction Act.

Signed into law in August 2022, the Inflation Reduction Act includes provisions requiring the federal government to negotiate prices for medications covered under Medicare Part D. Initial negotiations will target drugs with the highest total spending and price increases relative to inflation. In this study, we identify dermatology prescriptions with the highest cost burden on Medicare Part D and analyze recent trends in total spending and unit costs.

Access to Oncology Medicines in Canada: Consensus Forum for Recommendations for Improvement.

Patient access to new oncology drugs in Canada is only possible after navigating multiple sequential systemic checkpoints for national regulatory approval, health technology assessment (HTA) and collective government price negotiation. These steps delay access and prevent health care providers from being able to prescribe optimal therapy. Eighteen Canadian oncology clinicians from the medicine, nursing and pharmacy professions met to develop consensus recommendations for defining reasonable government performance standards around process and timeliness to improve Canadian cancer patients' access to best care. A modified Delphi methodology was used to identify consensus on 30 questions involving five themes: accountability, disparities, endpoints, timeliness, and cost-effectiveness. It was agreed that greater transparency is required across regulatory and HTA processes. Health professionals in oncology are frustrated for their patients because they are unable to deliver the modern guideline-supported therapies they want to provide due to delays in approval or funding. Canadian health care providers request improvements in timely access to life-saving therapeutics in line with other comparator countries. Clinicians expect urgent improvements in Canadian health systems to give our patients their best chance of survival.

Association between changes in prices and out-of-pocket costs for brand-name clinician-administered drugs.

OBJECTIVE: To determine whether annual changes in prices for clinician-administered drugs are associated with changes in patient out-of-pocket costs. DATA SOURCES AND STUDY SETTING: National commercial claims database, 2009 to 2018. STUDY DESIGN: In a serial, cross-sectional study, we calculated the annual percent change in manufacturer list prices and net prices after rebates. We used two-part generalized linear models to assess the relationship between annual changes in price with (1) the percentage of individuals incurring any out-of-pocket costs and (2) the percent change in median non-zero out-of-pocket costs. DATA COLLECTION/EXTRACTION METHODS: We created annual cohorts of privately insured individuals who used one of 52 brand-name clinician-administered drugs. PRINCIPAL FINDINGS: List prices increased 4.4%/yr (interquartile range [IQR], 1.1% to 6.0%) and net prices 3.3%/yr (IQR, 0.3% to 5.5%). The median percentage of patients with any out-of-pocket costs increased from 38% in 2009 to 48% in 2018, and median non-zero annual out-of-pocket costs increased by 9.6%/yr (IQR, 4.1% to 15.4%). There was no association between changes in prices and out-of-pocket costs for individual drugs. CONCLUSIONS: From 2009 to 2018, prices and out-of-pocket costs for brand-name clinician-administered drugs increased, but these were not directly related for individual drugs. This may be due to changes to insurance benefit design and private insurer drug reimbursement rates.

Drug pricing and transparency in Europe and the United States: what is it and how does it work?

INTRODUCTION: As drug prices are viewed to be opaque, there have been increasing societal demands on policy and decision makers to implement initiatives that promote drug price transparency. AREAS COVERED: This Perspective discusses what drug price transparency is and how it works in theory and in practice. EXPERT OPINION: Transparency on drug prices may target payers, patients and health care professionals; and may relate to prices at each stage in a drug's distribution system. Although proponents claim that drug price transparency will reduce prices and increase patient access, others expect the opposite effect. Nevertheless, a number of international organizations, countries and consumer groups have taken steps to enhance drug price transparency. This has occurred despite a lack of theoretical clarity and of evidence about its likely impact. Policy and decision makers need to consider how payers and pharmaceutical companies are likely to react to drug price transparency and need to be aware that transparency may produce different effects depending on the country to which it is applied. Even though we believe that full drug price transparency is elusive, various incremental measures can be taken to move toward it.

Trends in price for topical corticosteroids from 2017 to 2021 and the opportunity for cost savings identifiable at the point of care: A retrospective cross-sectional study.

BACKGROUND: Topical corticosteroids possess numerous generics and similar-strength substitutes. Affordability can impact obtaining the medication prescribed. OBJECTIVE: To determine recent trends in topical corticosteroid pricing and potential for cost saving. METHODS: A retrospective cross-sectional study analyzing all prescriptions dispensed for topical corticosteroids from January 1, 2017 through December 31, 2021, using a US all-payer pharmacy-claims database and commercial coupon dataset, was performed. RESULTS: Two hundred thirty-seven unique drug products (≥1 claim) were identified. Factors that predicted for higher cost (P < .05) were branded products (105% more expensive than generics) and ultrapotent class (55% more expensive than low potency) while ointments predicted for lower cost (19% less expensive than creams). Cash prices remained relatively stable, except for ultrapotent branded topical corticosteroids (63% increase). Cost savings were available for both brand-to-generic ($14.75 per unit) and generic-to-generic ($6.82 per unit) switching. Coupon prices were consistently lower than cash prices (r = 0.89). LIMITATIONS: Contracted rates through insurance plans were not included. CONCLUSIONS: Topical corticosteroid prices over the past 5 years have stabilized, the exception being branded ultrapotent corticosteroids. Savings from switching among similar-strength substitutes remain significant despite price stabilization. Coupon prices mirror the hierarchy of cash prices and can help assess real-time costs.

Stakeholder Perspectives of the Inflation Reduction Act's (2022) Impact on Prescription Drugs: A Narrative Review.

In this review, we examine the impact of the Inflation Reduction Act (IRA) of 2022 on pharmaceutical drugs in the United States, drawing on a diverse range of sources to understand the perceptions of multiple stakeholders and professionals. Findings suggest that the Act, while aiming to control price inflation, has had a multifaceted impact on the pharmaceutical sector. Stakeholders, including pharmaceutical companies, healthcare providers, patient advocacy groups, and policymakers, offered varied perspectives: while some laud the Act for its potential in controlling runaway drug prices and making healthcare more accessible, others raise concerns about possible reductions in drug innovation, disruptions to supply chains, and the sustainability of smaller pharmaceutical companies. The review identified four underlying constructs (themes) in the literature surrounding healthcare stakeholders' perceptions of the IRA's impact upon prescription drugs: pricing and/or dictation pricing issues, topics related to patent law and pharmaceuticals, processes surrounding the IRA's (2022) rules and regulations, and potential threats to the pharmaceutical industry concerning the research and development of future medications. The complex interplay of the Act's implications underscores the importance of ongoing assessment and potential iterative policy refinements as implementation endures.

Generic cardiology drug prices: the potential benefits of the Marc Cuban cost plus drug company model.

Introduction: Generic pharmaceuticals account for the majority of the $359 billion US pharmaceutical market, including for cardiology drugs. Amidst a lack of price transparency and administrative inefficiencies, generic drug prices are high, causing an undue burden on patients. Methods: We identified the 50 most used generic cardiology drugs by volume per the 2020 Medicare Part D spending data. We extracted cost per dose of each drug from the Marc Cuban Cost Plus Drug Company (MCCPDC) website and estimated the aggregate cost savings if MCCPDC were employed on a national scale by calculating the difference between this cost and Medicare spending. Results: Medicare spent $7.7 billion on the 50 most used generic cardiology drugs by volume in 2020 according to Medicare Part D data. Pharmacy and shipping costs accounted for a substantial portion of expenditures. Per our most conservative estimate, $1.3 billion (17% of total) savings were available on 16 of 50 drugs. A slightly less conservative estimate suggested $2.9 billion (38%) savings for 35 of 50 drugs. Discussion: There is enormous potential for cost savings in the US market for generic cardiology drugs. By encouraging increased competition, decreasing administrative costs, and advocating for our patients to compare prices between the MCCPDC and other generic pharmaceutical dispensers, we have the potential to improve access to care and corresponding outcomes for cardiology patients.

Therapeutic value of new medicines not submitted to Health Canada 2014-2021: Cross-sectional study.

OBJECTIVES: To examine whether there has been a change in the number of therapeutically important new medicines not being introduced into the Canadian market in light of the December 2017 announcement of regulatory changes to lower Canadian prices. METHODS: A list was compiled of medicines approved by the Food and Drug Administration (FDA) between 2014-2021 but not submitted to Health Canada. The therapeutic value of these medicines was assessed based on evaluations by two independent sources. If no evaluation was available, potential therapeutic value was determined based on the presence of one or more of three medicine characteristics. Interrupted time series was used to determine if there were changes in overall new medicine introductions and therapeutically important new medicines. RESULTS: The FDA approved 364 new medicines of which 116 (31.9%) were not submitted to Health Canada. There was a decrease in overall annual number of submissions but that was not related to the announcement at the end of 2017. There was no change in the introduction of therapeutically important new medicines as a percent of all medicines not marketed in Canada but there was a decrease in the absolute number. CONCLUSIONS: The number of therapeutically important medicines not being introduced into Canada is increasing but that is not related to the proposed price reforms.

Medicines for the People, not the Financial Markets.

Drug company marketing scandals have often made headlines. However, in recent years, a raft of new pharmaceutical industry transgressions has created crises for health care systems of high-income countries as well as poorer nations. Prices of life-saving drugs are soaring; supply shortfalls of essential medications have become common; development of new antibiotics against resistant organisms is lagging; and inequalities in access to medicines are widening. Policymakers must find new solutions to protect health systems and health.

Cancer Drug Prices in the United States: Efficacy, Innovation, Clinical Trial Evidence, and Epidemiology.

OBJECTIVES: Rising cancer drug prices challenge patients and healthcare systems. Although prices are routinely assigned to original drug indications receiving US Food and Drug Administration (FDA) approval, the pricing of supplemental indication approvals remains uncertain. This study identifies and quantifies factors associated with cancer drug prices, distinctly analyzing original and supplemental indications. METHODS: Clinical trial evidence and epidemiologic data supporting new indications' FDA approval (2003-2022) were collected from the Drugs@FDA database, ClinicalTrials.gov, and Global Burden of Disease study. Indication-specific monthly treatment costs were calculated for Medicare patients. The association between log-prices and collected variables were assessed in regression analyses. RESULTS: We identified 145 drugs approved across 373 cancer indications. Drugs were priced at $24 444 per month on average (median = $16 013). For original indications, prices weakly correlated to improvements in overall survival (ß = 0.28, P = .037) and progression-free survival (ß = 0.16, P = .001). Original indications' prices were as follows: (1) negatively associated with disease incidence (ß = -0.21, P < .001) and prevalence; (2) positively correlated with first-in-class drugs (26%, P = .057), gene and cell therapies (176%, P < .001), hematologic cancers (62%, P < .001), and severe diseases with substantial unmet needs (6% per disability-adjusted life-year, P < .001); and (3) negatively correlated to indications with randomized-controlled phase 3 trials. Prices were poorly associated with supplemental indications' efficacy, clinical evidence, and epidemiology. CONCLUSIONS: Cancer drug prices are set based on the original indication's characteristics, thereby omitting the value of supplemental indications. Indication-specific pricing, coverage, and reimbursement policies considering each indication's safety, efficacy, innovativeness, and unmet needs are necessary to align a drug's value and price.

Pharmaceutical Purchasing: a Review of the Landscape and Implications for Antidotal Therapies.

The management of the poisoned patient often requires the utilization of uncommonly used pharmaceutical interventions. These interventions can be associated with significant costs to both the patient and treating institution. Pharmaceutical supply shortages and issues with accessibility of antidotal therapies complicate the management of many toxic exposures. These challenges are an inherent property of the pharmaceutical purchasing infrastructure in the United States, which is a complicated network of public and private intra-institutional agreements. The cost and availability of any given therapy is dependent on the individual contracting agreements between the treating institution, payer, pharmacy benefit manager, manufacturer or wholesaler, and in some cases a specialty pharmacy. Small or remote hospitals may experience greater challenges related to insufficient patient volume to achieve predicable prescribing patterns of rare and expensive medications, necessitating consignment purchasing arrangements. Although pharmaceutical costs are the focus of recent legislative attention, these reforms are not expected to significantly alter the cost or availability of antidotal therapies.

Drug Cost-Effectiveness Assessments Require Standards for Rigor and Inclusion.

The Institute for Clinical and Economic Review (ICER), a nonprofit, nongovernmental organization, is the predominant independent price assessor in the United States. ICER's cost effectiveness assessments are increasingly being used to support health insurance coverage and healthcare policy decisions. ICER often does not apply rigorous data quality and inclusion criteria to either the assumptions embedded within their cost-effectiveness models or the data inputted into the models. Poor quality assumptions and data can lead to poor quality assessments. ICER should re-evaluate their reliance on quality adjusted life-years and equal value of life years gained as measures of drug effectiveness, establish data quality and inclusiveness minimum standards, produce cost-effectiveness assessments only when the minimum data is available, and prominently report data quality and inclusion limitations. These changes will increase the rigor and inclusiveness of drug price assessments and support sustainable access to high-value care for all Americans.

Orphan drugs' clinical uncertainty and prices: Addressing allocative and technical inefficiencies in orphan drug reimbursement.

Legislations incentivising orphan drug development and scientific advances have made orphan drugs pharma's high-end favourite for the past two decades. Currently, around 50% of new marketing authorizations are for orphan drugs. For third-party healthcare payers ("payers") the rise of orphan drugs presents new challenges, including a high degree of uncertainty around clinical benefits and harms, a moderate effect size (for many orphan drugs), and a high price tag. The association of high clinical uncertainty and moderate effect sizes is not surprising in small target populations but in combination with high prices creates the risk of allocative and technical inefficiencies for payers. We here discuss and illustrate these risks. A combination of policies is needed for mitigation of allocative inefficiency: while there may be a rationale for higher prices for orphan than non-orphan drugs, a focus of pricing and reimbursement negotiations should include considerations of product profitability and of the consequences of orphan drug costs on the distribution inequality of medication costs for individual insured persons, coupled to knowledge generation from reimbursement contracts covering high-price orphan drugs that would benefit the wider patient community. Performance-based managed entry agreements could help to de-risk the economic consequences of clinical uncertainty and to mitigate technical inefficiency.

A Pharmacoeconomic Outlook of the Biological Drugs Marketed in India: A Cost Variance Analysis.

Introduction Biologic drugs are used to treat various illnesses like autoimmune diseases, cancers, hormonal irregularities, anemia, etc., and to prevent various diseases as vaccines. Though various biologic drugs are already available, they are still not within reach of the common man due to financial constraints. Through many search engines, studies evaluating the cost variation of different brands of biologics were investigated; however, only a few studies that address this problem were found. Hence, this study was planned with the objective of addressing the cost variation of various brands of biologic medicines available in the Indian market. Methods The website for the Current Index of Medical Specialties (CIMS) for India's location was used to obtain the prices of the different brands of biologic medicines in Indian National Rupee (INR) currency, which different manufacturers market with identical forms in strength and dosage. The percentage cost variation and cost ratio were calculated with the help of the minimum and maximum prices of various brands of biologic drugs. Results The prices of biologics belonging to six different classes that are available in 23 formulations were analyzed. The highest cost variability was shown by pegfilgrastim 6 mg at 1,022.92%, and the minimum-cost variation was shown by darbepoetin alfa 200 mcg at 13.07%. Conclusion Our research found a vast variance in the costs of various brands of biologic medicines in India. The government should address this cost variation problem by developing various policies, such as breaking the monopoly of manufacturers, providing tax incentives to nonprofit generic medicine manufacturers, and incorporating more biologic drugs under the protection of the Drugs Prices Control Order (DPCO).

The Effect of the Drug Life Cycle Price on Cost-Effectiveness: Case Studies Using Real-World Pricing Data.

OBJECTIVES: Cost-effectiveness analyses (CEAs) generally assume constant drug prices throughout the model time horizon, yet it is known that prices are not constant, often with price decreases near loss of exclusivity (LOE). This study explores the impact of using dynamic drug-specific prices on the incremental cost-effectiveness ratio (ICER) using selected reproduced case studies. METHODS: Case studies were selected following explicit criteria to reflect a variety of drug characteristics. For each drug, a published CEA model was identified, replicated, and modified with dynamic real-world pricing data, to compare ICERs based on constant drug prices with estimates obtained when including drug life cycle pricing. The impact of dynamic real-world pricing-inclusive LOE-was analyzed using a single patient cohort and multiple cohorts over time. RESULTS: Fluvastatin, alendronic acid + colecalciferol combination therapy, letrozole and clopidogrel were selected as case studies. Inclusion of real-world pricing data compared with applying constant prices reduced the ICER in a single-cohort setting up to 43%. In the multicohort analyses, further reductions of the ICERs were observed of up to 113%. The ICERs were sensitive to the period of drug usage relative to the models' time horizons, the relative proportions of drug costs in the overall treatment costs, and timing of LOE compared with the cost year of the original analysis. CONCLUSIONS: Assuming dynamic drug prices may lead to more representative ICER estimates. Future CEAs for drugs could account for predicted and disaggregated life cycle price developments based on retrospective data.

Addressing High Drug Prices by Reforming Pharmacy Benefit Managers.

Recently, Congress has focused on reforms to address pharmacy benefit managers' (PBMs) role in high drug prices for patients. Congress must not excessively restrict PBMs' ability to negotiate with manufacturers; alternatively, reforms could be paired with other policies that address the high prices of brand-name drugs.

Pharmacy Benefit Management: The Cost of Drug Price Rebates.

Pharmacy Benefit Managers (PBM) induce drug manufacturers to offer rebates to insurers and employers by denying coverage through formulary exclusions, impeding physician prescription through prior authorization, and reducing patient drug use through cost sharing. As they tighten these access obstacles, PBMs reduce the net prices received by the manufacturers.