Analysis of US Food and Drug Administration new drug and biologic approvals, regulatory pathways, and review times, 1980-2022.

U.S. laws enacted since 1983 have aimed to enhance the development and marketing of new pharmaceutical products. We thoroughly characterized all new molecular entities, therapeutic biologics, and gene and cell therapies approved by the US Food and Drug Administration (FDA) during the period 1980-2022 in the context of these laws and regulations. Throughout the study period, the FDA approved 1355 new pharmaceutical products. The median FDA review time decreased from 26.6 months prior to the Prescription Drug User Fee Act (1992), which authorized the FDA to collect fees from drug companies to 9.9 months after the Food and Drug Administration Safety and Innovation Act (2012), which created new designations that eliminated the requirement for evidence of added therapeutic benefit for FDA expedited drug review. The greatest increase in approvals occurred in antineoplastic and immunomodulating drugs, biologics, and orphan drugs. More than half of new drug approvals benefited from regulatory designations and pathways that did not require addressing unmet medical needs or demonstrating therapeutic benefit over available alternatives. The legislative goal of bringing more drugs to the market faster has been achieved. Further studies are needed to determine the therapeutic value to patients of new drugs approved using expedited approval pathways.

A Comparative Assessment of Approvals and Discontinuations of Systemic Antibiotics and Other Therapeutic Areas.

Since 1980, the US Congress has passed legislation providing several incentives to encourage the development and regulatory approval of new drugs, particularly antibiotics. We assessed long-term trends and characteristics of approvals and discontinuations of all new molecular entities, new therapeutic biologics, and gene and cell therapies approved by the US Food and Drug Administration (FDA), as well as reasons for discontinuations by therapeutic class, in the context of laws and regulations implemented over the past four decades. In the period 1980-2021, the FDA approved 1310 new drugs, of which 210 (16.0%) had been discontinued as of 31 December 2021, including 38 (2.9%) withdrawn for safety reasons. The FDA approved 77 (5.9%) new systemic antibiotics, of which 32 (41.6%) had been discontinued at the end of the observation period, including 6 (7.8%) safety withdrawals. Since the enactment of the FDA Safety and Innovation Act in 2012, which created the Qualified Infectious Disease Product designation for antiinfectives to treat serious or life-threatening diseases due to resistant or potentially resistant bacteria, the FDA has approved 15 new systemic antibiotics, all using non-inferiority trials, for 22 indications and five different infections. Only one of the infections had labeled indications for patients with drug-resistant pathogens.

Analysis of the Gene Therapies Authorized by the United States Food and Drug Administration and the European Medicines Agency.

BACKGROUND: Gene therapy, altering the genes inside human cells, has recently emerged as an alternative for preventing and treating disease. Concerns have been expressed about the clinical value and the high cost of gene therapies. OBJECTIVE: This study assessed the characteristics of the clinical trials, authorizations, and prices of gene therapies in the United States and the European Union. RESEARCH DESIGN: We collected regulatory information from the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and manufacturer-listed prices from the United States, UK, and Germany. Descriptive statistics and t tests were conducted in the study. RESULTS: As of January 1, 2022, the FDA and EMA authorized 8 and 10 gene therapies, respectively. The FDA and EMA granted orphan designation to all gene therapies except talimogene laherparepvec. Pivotal clinical trials were nonrandomized, open level, uncontrolled, phase I-III, and included a limited number of patients. Study primary outcomes were mainly surrogate endpoints without demonstration of direct patient benefit. The price of gene therapies at market entry ranged from $200,064 to $2,125,000 million. CONCLUSIONS: Gene therapy is used to treat incurable diseases that affect only a small number of patients (orphan diseases). Based on this, they are approved by the EMA and FDA with insufficient clinical evidence to ensure safety and efficacy, in addition to the high cost.

Assessment of FDA-Approved Drugs Not Recommended for Use or Reimbursement in Other Countries, 2017-2020.

Importance: Drug expenditures in the US are higher than in any other country and are projected to continue increasing, so US health systems may benefit from evaluating international regulatory and reimbursement decision-making of new drugs. Objective: To evaluate regulatory decisions and health technology assessments (HTAs) in Australia, Canada, and the UK regarding new drugs approved by the US Food and Drug Administration (FDA) in 2017 through 2020, as well as to estimate the US cost per patient per year for drugs receiving negative recommendations. Design and Setting: In this cross-sectional study, recommendations issued by agencies in Australia, Canada, and the UK were collected for new drugs approved by the FDA in 2017 through 2020. All data were current as of May 31, 2022. Exposures: Authorizations and HTAs in selected countries. Main Outcomes and Measures: All FDA-approved drugs were matched by active ingredient to decision summary reports published by drug regulators and HTA agencies in Australia, Canada, and the UK. Regulatory approval concordance and reasons for negative recommendations were assessed using descriptive statistics. For drugs not recommended by an international agency, the annual US drug cost per patient was estimated from FDA labeling and wholesale acquisition costs. Results: The FDA approved 206 new drugs in 2017 through 2020, of which 162 (78.6%) were granted marketing authorization by at least 1 other regulatory agency at a median (IQR) delay of 12.1 (17.7) months following US approval. Conversely, 5 FDA-approved drugs were refused marketing authorization by an international regulatory agency due to unfavorable benefit-to-risk assessments. An additional 42 FDA-approved drugs received negative reimbursement recommendations from HTA agencies in Australia, Canada, or the UK due to uncertainty of clinical benefits or unacceptably high prices. The median (IQR) US cost of the 47 drugs refused authorization or not recommended for reimbursement by an international agency was $115 281 ($166 690) per patient per year. Twenty drugs were for oncology indications, and 36 were approved by the FDA through expedited regulatory pathways or the Orphan Drug Act. Conclusions and Relevance: This cross-sectional study assessed reasons for which drugs recently approved by the FDA were refused marketing authorization or not recommended for public reimbursement in other countries. Drugs with limited international market presence may require close examination by US health care professionals and health systems.

Disentangling the Cost of Orphan Drugs Marketed in the United States.

The increasing number and high prices of orphan drugs have triggered concern among patients, payers, and policymakers about the affordability of new drugs approved using the incentives set by the Orphan Drug Act (ODA) of 1983. This study evaluated the factors associated to the differences in the treatment cost of new orphan and non-orphan drugs approved by the FDA from 2017 to 2021. A generalized linear model (GLM) with the Gamma log-link analysis was used to ascertain the association of drug characteristics with the treatment costs of orphan and non-orphan drugs. The results of the study showed that the median and interquartile range (IQR) drug cost was USD 218,872 (IQR = USD 23,105) for orphan drugs and USD 12,798 (IQR = USD 57,940) for non-orphan drugs (p < 0.001). Higher market entry prices were associated with biologics (108%; p < 0.001), orphan status (177%; p < 0.001), US sponsor companies (48%; p = 0.035), chronic use (1083%; p < 0.001), treatment intent (163%; p = 0.004), and indications for oncology (624%; p < 0.001) or genetic disorders (624%; p < 0.001). Higher market entry treatment cost for newly approved drugs were associated with biologics, orphan status, US sponsor companies, chronic use, therapeutic intent, and indications for oncology or genetic disorders.

Cost-effectiveness analysis of androgen deprivation therapy with relugolix for the treatment of advanced prostate cancer.

BACKGROUND: Relugolix treatment of advanced prostate cancer (APC), like other gonadotropin-releasing hormone-antagonists, results in rapid decrease in testosterone concentrations without the risk of flare, as seen in leuprolide. Despite this benefit over leuprolide, no economic evaluation assessment to ascertain the cost-effectiveness of relugolix has been conducted. Therefore, this study aims to assess the cost-effectiveness of androgen deprivation therapy (ADT) with 120 mg relugolix against 7.5 mg leuprolide for the treatment of APC. METHODS: A Markov model was used to assess and compare the costs of APC treatment from a health care payer's perspective and the effectiveness of ADT with relugolix and leuprolide at the 3 lines of APC treatment among modified intent-to-treat patients. Relative progression-free (PFS) and overall survival (OS) rates were estimated. Outcomes measured in the analyses included costs of the drugs and therapies, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), cost-effectiveness acceptability, and probability curves. RESULTS: The cost-effectiveness analysis showed the ICER for ADT with relugolix to be US $49,571.1 per QALY. At the ICER value, the sensitivity analysis indicated that ADT with leuprolide was dominant in 100% of the simulations. ADT acceptance with relugolix was 100% when a willingness-to-pay threshold was set at US $100,000/QALY. At 5-years, the relative PFS and OS rates for relugolix at the first line of therapy were 72.7% and 86.0%, respectively, compared to 61.0% and 85.90% for leuprolide. CONCLUSION: Though the influence of adverse events was not considered in the analysis, ADT with relugolix was not a cost-effective choice for APC management. While the analysis revealed a slight chance of sustaining testosterone suppression with relugolix, ADT with relugolix provided no significant survival advantages over ADT with leuprolide. Therefore, this analysis confirms no need for further assessment of APC interventions to make informed decisions beneficial to the APC patients, oncologists, and other stakeholders.

Exploratory Analysis of Outpatient Visits for US Adults Diagnosed with Lupus Erythematosus: Findings from the National Ambulatory Medical Care Survey 2006-2016.

The study aims to assess office-based visit trends for lupus patients and evaluate their medication burden, chronic conditions, and comorbidities. This cross-sectional study used data from the National Ambulatory Medical Care Survey (NAMCS), a survey sample weighted to represent national estimates of outpatient visits. Adult patients diagnosed with lupus were included. Medications and comorbidities that were frequently recorded were identified and categorized. Descriptive statistics and bivariate analyses were used to characterize visits by sex, age, race/ethnicity, insurance type, region, and reason for visit. Comorbidities were identified using diagnosis codes documented at each encounter. There were 27,029,228 visits for lupus patients from 2006 to 2016, and 87% them were on or were prescribed medications. Most visits were for female (88%), white (79%), non-Hispanic (88%) patients with private insurance (53%). The majority of patients were seen for a chronic routine problem (75%), and 29% had lupus as the primary diagnosis. Frequent medications prescribed were hydroxychloroquine (30%), prednisone (23%), multivitamins (14%), and furosemide (9%). Common comorbidities observed included arthritis (88%), hypertension (25%), and depression (13%). Prescription patterns are reflective of comorbidities associated with lupus. By assessing medications most frequently prescribed and comorbid conditions among lupus patients, we showcase the complexity of disease management and the need for strategies to improve care.

Postoperative Respiratory Events in Surgical Patients Exposed to Opioid Analgesic Shortages Compared to Fully Matched Patients Non-exposed to Shortages.

INTRODUCTION: Shortages of opioid analgesics critically disrupt clinical practice and are detrimental to patient safety. There is a dearth of studies assessing the safety implications of drug shortages. OBJECTIVE: We aimed to assess perioperative opioid analgesic use and related postoperative hypoxemia (oxygen saturation less than 90%) in surgical patients exposed to prescription opioid shortages compared to propensity score-matched patients non-exposed to opioid shortages. METHODS: We conducted a retrospective study including adult patients who underwent elective surgery at The University of California San Francisco in the period August 2018-December 2019. We conducted a Gamma log-link generalized linear model to assess the effect of shortages on perioperative use of opioids and a weighted logistic regression to assess the likelihood of experiencing postoperative hypoxemia. RESULTS: There were 1119 patients exposed to opioid shortages and 2787 matched non-exposed patients. After full matching, patients exposed to shortages used a greater mean of morphine milligram equivalents/day (146.94; 95% confidence interval 123.96-174.16) than non-exposed patients (117.92; 95% confidence interval 100.48-138.38; p = 0.0001). The estimated effect was a 1.25 (95% confidence interval 1.12-1.40; p = 0.0001) times greater use of opioids in patients exposed to opioid shortages than non-exposed patients. After full matching, a greater proportion of patients exposed to shortages (19.06%) experienced hypoxemia compared with non-exposed patients (16.91%). In addition, a greater proportion of patients exposed to opioid shortages (1.20%) experienced hypoxemia reversed by intravenous naloxone administration compared with non-exposed patients (0.44%). CONCLUSIONS: Given the shortage prevalence, reliance on opioid medications, and related risk of respiratory depression, harm prevention measures remain critical to prevent postoperative complications that may compromise patients' safety.

Predictors of shortages of opioid analgesics in the US: Are the characteristics of the drug company the missing puzzle piece?

BACKGROUND: Shortages of opioid analgesics are increasingly common, interfere with patient care and increase healthcare cost. This study characterized the incidence of shortages of opioid analgesics in the period 2015-2019 and evaluated potential predictors to forecast the risk of shortages. METHODS: This was an observational retrospective study using the US Food and Drug Administration (FDA) drug shortages data. All FDA approved opioids were included in the study. Opioid analgesics were identified using the FDA National Drug Codes (NDC) and classified according to the Drug Enforcement Administration (DEA) schedule. We conducted Least Absolute Shrinkage and Selection Operator logistic regression analysis to assess direction of the association between risk of shortage and potential predictors. We used multivariable penalized logistic regression analysis to model predictors of shortages. We split the dataset into training and validation sets to evaluate the performance of the model. FINDINGS: The FDA approved 8,207 unique NDCs for opioid analgesics; 3,017 (36.8%) were in the market as of April 30, 2019 and 91(3.0%) of them were listed as in shortage by the FDA. All NDCs in shortage were schedule II opioids; 86 (94.5%) were injectable and 84 (92.3%) generics. There were 418 companies with at least one opioid NDC listed by the FDA. Three companies accounted for more than 4 in 5 of the schedule II active injectable opioids. For each unit increase in the number of prior instances of shortages of a company, the likelihood of an NDC shortage for that company increased by 3.4%. For each unit increase in number of NDCs marketed by a company, the odds of an NDC shortage for that company decreased by 1%. CONCLUSIONS: In the period 2015-2019, shortages of opioid analgesics disproportionally impacted schedule II and injectable opioids. The risk of shortage of opioid analgesics significantly increased with the incidence of previous instances of shortages of a manufacturing company and decreased with the number of NDCs marketed by a company. The characteristics of the manufacturing company, rather than the number of companies, might be the missing piece to the complex puzzle of drug shortages in the US.

Effect of free trade agreements on pharmaceutical market competition: The case of the 2009 US-Peru free trade agreement and its implementation as national drug policy.

Free Trade Agreements (FTA) are controversial for threatening essential aspects of health, especially access to affordable medicines. The US-Peru FTA required changes in the Peruvian pharmaceutical legislation that resulted in the implementation of the National Drug Policy (NDP) of 2009. The NDP included more robust technical requirements for registration, a Peruvian Good Manufacturing Practices certificate, a longer timeline for drug registration, and an increase in registration fees. This study evaluated the impact of the FTA on the number of registrations and competition in the Peruvian pharmaceutical market. Data for the period January 2005 to April 2014 were provided by the Peruvian drug regulatory authority (Dirección General de Medicamentos, Insumos y Drogas, DIGEMID). A total of 31,114 pharmaceutical products with unique registration numbers were evaluated. Brand drug new registrations decreased from 1789 in 2005 to 455 in 2013, and the number of generic registrations decreased from 621 in 2005 to 114 in 2013. Brand re-registrations also decreased from 714 in 2005 to 58 in 2013. There were 228 brand products awaiting registration in 2009 and 1,908 in 2013. The proportion of products awaiting registration was three times greater for brand than for generic products in 2009-2013. Registration of brand and generic medicines significantly declined after the implementation of the US-Peru FTA in 2009. The decline in the number of registrations was associated with more robust technical requirements, a longer DIGEMID registration timeline, and an increase in registration fees. The stronger registration requirements are expected to increase the quality of the drugs marketed in the country, but also less competition and a reduction in domestic registrations.

Perioperative Prescribing Practices of Extended-Release Opioids in Noncancer Surgical Patients, 2015-2018.

BACKGROUND: Extended-release (ER) opioids are indicated for the management of persistent moderate to severe pain in patients requiring around-the-clock opioid analgesics for an extended period of time. Concerns have been raised regarding safety of ER opioids due to its potential for abuse and dependence. However, little is known about perioperative prescribing practices of ER opioids. This study assessed perioperative prescribing practices of ER opioids in noncancer surgical patients stratified by type of opioid exposure prior to admission and examined predictors of postoperative opioid administration in oral morphine equivalents (OME). METHODS: This was a retrospective cohort study using the University of California San Francisco Medical Center electronic health record data. This study included 25,396 adult noncancer patients undergoing elective surgery under general anesthesia in the period 2015-2018. The primary study outcome was predictors of postoperative administration of opioids in hospitalized surgical patients. Secondary outcomes included patients discontinued and initiated on ER opioids during their hospital stay. RESULTS: substance use disorder diagnosis and use of opioids, surgery type, and postoperative administration of nonopioid analgesics were associated with postoperative administration of opioids (P < .0001). The estimated adjusted mean (95% confidence interval [CI]) of postoperative administration of OME prior to admission in ER opioid users (170.08 mg; 147.08-196.67) was twice the amount for opioid-naïve patients (81.36 mg; 70.7-93.63; P < .0001). One in 5 prior to admission ER opioid users were weaned off ER opioids while hospitalized without adversely affecting their postoperative pain or hospital length of stay (LOS). Four of 5 patients who used ER opioids prior to admission also received ER opioids after surgery, whereas, 1 in 100 opioid-naïve patients received ER opioids during their hospital stay. CONCLUSIONS: We found significant variability in the perioperative prescribing practices of ER opioids in hospitalized noncancer surgical patients by use of opioids prior to admission and surgery type. Pain medicine practitioners and surgeons may play a significant role tackling the surgery-related risk of exposure to ER opioids and decreasing opioid-related complications.

Using a Machine Learning System to Identify and Prevent Medication Prescribing Errors: A Clinical and Cost Analysis Evaluation.

BACKGROUND: Clinical decision support (CDS) alerting tools can identify and reduce medication errors. However, they are typically rule-based and can identify only the errors previously programmed into their alerting logic. Machine learning holds promise for improving medication error detection and reducing costs associated with adverse events. This study evaluates the ability of a machine learning system (MedAware) to generate clinically valid alerts and estimates the cost savings associated with potentially prevented adverse events. METHODS: Alerts were generated retrospectively by the MedAware system on outpatient data from two academic medical centers between 2009 and 2013. MedAware alerts were compared to alerts in an existing CDS system. A random sample of 300 alerts was selected for medical record review. Frequency and severity of potential outcomes of alerted medication errors of medium and high clinical value were estimated, along with associated health care costs of these potentially prevented adverse events. RESULTS: A total of 10,668 alerts were generated. Overall, 68.2% of MedAware alerts would not have been generated by the existing CDS system. Ninety-two percent of a random sample of the chart-reviewed alerts were accurate based on structured data available in the record, and 79.7% were clinically valid. Estimated cost of adverse events potentially prevented in an outpatient setting was more than $60 per drug alert and $1.3 million when extrapolating study findings to the full patient population. CONCLUSION: A machine learning system identified clinically valid medication error alerts that might otherwise be missed with existing CDS systems. Estimates show potential for cost savings associated with potentially prevented adverse events.

The Landscape of Cellular and Gene Therapy Products: Authorization, Discontinuations, and Cost.

Background: Cell and gene therapy products belong to a diverse class of biopharmaceuticals known as advanced therapy medicinal products. Cell and gene therapy products are used for the treatment and prevention of diseases that until recently were only managed chronically. The objective of this study was to examine the characteristics of market authorizations, discontinuations, and prices of cellular and gene therapy products worldwide. Data and Methods: We conducted an electronic search of authorized cell, tissue-engineered, and gene therapy products from the databases of the main drug regulatory agencies. The analysis excluded hematopoietic progenitor cell cord blood products authorized by the U.S. Food and Drug Administration. Price information was derived from the Red Book (Truven Health Analytics) for the United States, health technology assessment agencies for Europe, and other public sector sources and company news for other countries. We also searched the scientific literature for authorizations, discontinuations, and price information using MEDLINE/PubMed, Cochrane Library, Google Scholar, and EMBASE databases. All cost data were converted to U.S. dollars. Descriptive analysis was conducted in this study. Results: There were 52 different cell, tissue engineering and gene therapy products with 69 market authorizations in the world as of December 31, 2018. The products included 18 (34%) cell therapies, 23 (43.4%) tissue engineered products, and 12 (22.6%) gene therapies. There were 21 (30.4% of all authorizations) cell therapy, 26 (37.7%) tissue-engineered, and 22 (31.9%) gene therapy market authorizations. The EMA withdrew the authorization for two tissue engineering products, one cell therapy and one gene therapy, and New Zealand lapsed approval of one cell therapy. Most products were first authorized after 2010, including 10 (83.3%) gene therapies, 13 (72.2%) cell therapies, and 13 (56.5%) tissue-engineered products. The treatment price for four allogenic cell therapies varied from $2,150 in India to $200,000 in Canada. The treatment price for three autologous cell therapies ranged from $61,500 in the United Kingdom to a listed price of $169,206 in the United States. Tissue-engineered treatment prices varied from $400 in South Korea to $123,154 in Japan. Gene therapy treatment prices ranged from $5,501 for tonogenchoncel-L in South Korea to $1,398,321 for alipogene tiparvovec in Germany. Conclusions: A significant number of new cell, tissue, and gene therapies have been approved in the past decade. Most products were conditionally authorized and targeted rare cancers, genetic diseases, and other debilitating diseases. However, there are also products approved for cosmetic reasons. Cell, tissue, and gene therapies are among the most expensive therapies available. Healthcare systems are not prepared to assume the cost of future therapies for a myriad of rare diseases and common diseases of epidemic proportions.

Impact of an Advanced Practice Pharmacist Type 2 Diabetes Management Program: A Pilot Study.

BACKGROUND: The purpose of this study was to describe the impact of an Advanced Practice Pharmacist (APh) on lowering hemoglobin A1c (HbA1c) in patients with type 2 diabetes within a patient centered medical home (PCMH) and to classify the types of therapeutic decisions made by the APh. METHODS: This was a retrospective study using data from electronic health records. The study evaluated a partnership between Chapman University School of Pharmacy and Providence St. Joseph Heritage Healthcare that provided diabetes management by an Advanced Practice Pharmacist in a PCMH under a collaborative practice agreement. Change in the HbA1c was the primary endpoint assessed in this study. The type of therapeutic decisions made by the APh were also evaluated. Descriptive analysis and Wilcoxon signed ranktest were used to analyze data. RESULTS: The study included 35 patients with diagnosis of type 2 diabetes mellitus managed by an APh from May 2017 to December 2017. Most of the patients were 60-79 years old (68.5%), 45.7% were female, and 45.7% were of Hispanic/Latino ethnicity. The average HbA1cwas 8.8%±1.4% (range=6.0%-12.4%) and 7.5%±1.4% (range=5.5%-12.4%) at the initial and final APh visit, respectively (p<0.0001). Therapeutic decisions made by the APh included drug dose increase (35.5% of visits), drug added (16.4%), drug dose decrease (6.4%), drug switch (5.5%), and drug discontinuation (1.8%). CONCLUSION: The Advanced Practice Pharmacist's interventions had a significant positive impact on lowering HbA1c in patients with type 2 diabetes mellitus in a PCMH. The most common therapeutic decisions made by the APh included drug dose increase and adding a new drug.

Changes in the utilization of osteoporosis drugs after the 2010 FDA bisphosphonate drug safety communication.

INTRODUCTION: In October 2010, the US Food and Drug Administration (FDA) issued a safety communication regarding the risks of atypical fractures of the femur, with bisphosphonates drugs. This study evaluated the impact of the bisphosphonates FDA safety communication on the utilization of osteoporosis medications in Medicaid programs. METHODS: Osteoporosis drugs utilization data from the July 2006 to June 2014 were extracted from the national Summary Files from the Medicaid State Drug Utilization Data maintained by the Centers for Medicare & Medicaid Services (CMS). We performed an interrupted time series analyses to evaluate trends in utilization of osteoporosis drugs before and after the 2010 FDA safety commination. RESULTS: Time-series analyses of osteoporosis drug utilization in Medicaid program revealed a significant downward trend associated with the 2010 FDA bisphosphonates safety communication. Before the FDA safety communication was issued, the utilization rate was slightly decreased between 2006 and 2010. In the year following the FDA safety communication the bisphosphonate DDDs per 1000 beneficiaries of fell 22% yearly until the end of study period. CONCLUSIONS: The 2010 FDA bisphosphonates safety communication appeared to have influenced Osteoporosis utilization in Medicaid recipients. The 2010 FDA bisphosphonates safety communication was associated with a significant reduction in the utilization of bisphosphonates in the Medicaid program.

Incorporating medication indications into the prescribing process.

PURPOSE: The incorporation of medication indications into the prescribing process to improve patient safety is discussed. SUMMARY: Currently, most prescriptions lack a key piece of information needed for safe medication use: the patient-specific drug indication. Integrating indications could pave the way for safer prescribing in multiple ways, including avoiding look-alike/sound-alike errors, facilitating selection of drugs of choice, aiding in communication among the healthcare team, bolstering patient understanding and adherence, and organizing medication lists to facilitate medication reconciliation. Although strongly supported by pharmacists, multiple prior attempts to encourage prescribers to include the indication on prescriptions have not been successful. We convened 6 expert panels to consult high-level stakeholders on system design considerations and requirements necessary for building and implementing an indications-based computerized prescriber order-entry (CPOE) system. We summarize our findings from the 6 expert stakeholder panels, including rationale, literature findings, potential benefits, and challenges of incorporating indications into the prescribing process. Based on this stakeholder input, design requirements for a new CPOE interface and workflow have been identified. CONCLUSION: The emergence of universal electronic prescribing and content knowledge vendors has laid the groundwork for incorporating indications into the CPOE prescribing process. As medication prescribing moves in the direction of inclusion of the indication, it is imperative to design CPOE systems to efficiently and effectively incorporate indications into prescriber workflows and optimize ways this can best be accomplished.

Cost-effectiveness analysis of metformin+dipeptidyl peptidase-4 inhibitors compared to metformin+sulfonylureas for treatment of type 2 diabetes.

BACKGROUND: Patients with type 2 diabetes (T2D) typically use several drug treatments during their lifetime. There is a debate about the best second-line therapy after metformin monotherapy failure due to the increasing number of available antidiabetic drugs and the lack of comparative clinical trials of secondary treatment regimens. While prior research compared the cost-effectiveness of two alternative drugs, the literature assessing T2D treatment pathways is scarce. The purpose of this study was to evaluate the long-term cost-effectiveness of dipeptidyl peptidase-4 inhibitors (DPP-4i) compared to sulfonylureas (SU) as second-line therapy in combination with metformin in patients with T2D. METHODS: A Markov model was developed with four health states, 1 year cycle, and a 25-year time horizon. Clinical and cost data were collected from previous studies and other readily available secondary data sources. The incremental cost-effectiveness ratio (ICER) was estimated from the US third party payer perspective. Both, costs and outcomes, were discounted at a 3% annual discount rate. One way and probabilistic sensitivity analyses were performed to evaluate the impact of uncertainty on the base-case results. RESULTS: The discounted incremental cost of metformin+DPP-4i compared to metformin+SU was $11,849 and the incremental life-years gained were 0.61, resulting in an ICER of $19,420 per life-year gained for patients in the metformin+DPP-4i treatment pathway. The ICER estimated in the probabilistic sensitivity analysis was $19,980 per life-year gained. Sensitivity analyses showed that the results of the study were not sensitive to changes in the parameters used in base-case. CONCLUSIONS: The metformin+DPP-4i treatment pathway was cost-effective compared to metformin+SU as a long-term second-line therapy in the treatment of T2D from the US health care payer perspective. Study findings have the potential to provide clinicians and third party payers valuable evidence for the prescription and utilization of cost-effective second-line therapy after metformin monotherapy failure in the treatment of T2D.