The economic impact of suboptimal treatment and treatment switch among patients with Crohn's disease treated with a first-line biologic - A US retrospective claims database study.

AIMS: Suboptimal treatment indicators, including treatment switch, are common among patients with Crohn's disease (CD), but little is known about their associated healthcare resource utilization (HRU) and costs. This study assessed the impact of suboptimal treatment indicators on HRU and costs among adults with CD newly treated with a first-line biologic. METHODS: Adult patients with CD were identified in the IBM MarketScan Commercial Subset (10/01/2015-03/31/2020). The index date was defined as initiation of the first-line biologic, and the study period was defined as the 12 months following the index date. Patients were classified into Suboptimal Treatment and Optimal Treatment cohorts based on observed indicators of suboptimal treatment during the study period. Patients in the Suboptimal Treatment Cohort with a treatment switch were classified into the Treatment Switch Cohort and compared to patients with no treatment switch. All-cause HRU and costs were measured during the study period and assessed for patients with suboptimal vs optimal treatment and patients with vs without a treatment switch. RESULTS: The study included 4,006 patients (Suboptimal Treatment: 2,091, Optimal Treatment: 1,915). Treatment switch was a common indicator of suboptimal treatment (Treatment Switch: 640, No Treatment Switch: 3,366). HRU and costs were significantly higher among patients with suboptimal treatment than those with optimal treatment (annual costs: $92,043 vs $73,764; p < 0.01), and among those with a treatment switch than those with no treatment switch (annual costs: $95,689 vs $81,027; p < 0.01). Increases in the number of suboptimal treatment indicators were associated with increased costs. LIMITATIONS: Claims data were used to identify suboptimal treatment indicators based on observed treatment patterns; reasons for treatment decisions could not be assessed. CONCLUSION: This study demonstrates that patients with suboptimal treatment indicators, including treatment switch, incur substantially higher HRU and costs compared to patients receiving optimal treatment and those that do not switch treatments.

Cost of genetic testing, delayed care, and suboptimal treatment associated with polymerase chain reaction versus next-generation sequencing biomarker testing for genomic alterations in metastatic non-small cell lung cancer.

AIMS: To assess US payers' per-patient cost of testing associated with next-generation sequencing (NGS) versus polymerase chain reaction (PCR) biomarker testing strategies among patients with metastatic non-small cell lung cancer (mNSCLC), including costs of testing, delayed care, and suboptimal treatment initiation. METHODS: A decision tree model considered biomarker testing for genomic alterations using either NGS, sequential PCR testing, or hotspot panel PCR testing. Literature-based model inputs included time-to-test results, costs for testing/medical care, costs of delaying care, costs of immunotherapy [IO]/chemotherapy [CTX] initiation prior to receiving test results, and costs of suboptimal treatment initiation after test results (i.e. costs of first-line IO/CTX in patients with actionable mutations that were undetected by PCR that would have been identified with NGS). The proportion of patients testing positive for a targetable alteration, time to appropriate therapy initiation, and per-patient costs were estimated for NGS and PCR strategies combined. RESULTS: In a modeled cohort of 1,000,000 members (25% Medicare, 75% commercial), an estimated 1,119 had mNSCLC and received testing. The proportion of patients testing positive for a targetable alteration was 45.9% for NGS and 40.0% for PCR testing. Mean per-patient costs were lowest for NGS ($8,866) compared to PCR ($18,246), with lower delayed care costs of $1,301 for NGS compared to $3,228 for PCR, and lower costs of IO/CTX initiation prior to receiving test results (NGS: $2,298; PCR:$5,991). Cost savings, reaching $10,496,220 at the 1,000,000-member plan level, were driven by more rapid treatment with appropriate therapy for patients tested with NGS (2.1 weeks) compared to PCR strategies (5.2 weeks). LIMITATIONS: Model inputs/assumptions were based on published literature or expert opinion. CONCLUSIONS: NGS testing was associated with greater cost savings versus PCR, driven by more rapid results, shorter time to appropriate therapy initiation, and minimized use of inappropriate therapies while awaiting and after test results.

Risks of suboptimal and excessive thyroid hormone replacement across ages.

BACKGROUND: Hypothyroidism is prevalent at all ages and represents a non-communicable disease with preventable consequences. METHOD: Narrative review. REVIEW: In children and adolescents, the most devastating consequences of undertreatment with levothyroxine (LT4) are poor growth and development. Delayed treatment in congenital hypothyroidism can lead to permanent brain damage. In young to middle-aged adults, symptoms are often overlooked, and treatment delayed by many years. The resulting consequences are also at this age group compromised brain and physical function but less severe and partly reversible with treatment. The under-treated condition often results in a higher risk of, e.g., increased cardiovascular disease burden, obesity, hypertension, poor physical capacity, and poor quality of life. Excessive replacement is at all adult age groups associated with increased risk of cardiac death, osteoporosis, loss of muscle function, psychological instability and poor quality of life. In young fertile women, the consequences of undertreatment with LT4 are subnormal fertility, recurrent pregnancy loss, compromised fetal growth, and neurocognitive development. On the other hand, excessive LT4 treatment has been related to gestational hypertension, preeclampsia and preterm birth. In the elderly, care must be given to avoid confusing a slightly high age-related serum TSH with requirement for LT4 treatment in a truly hypothyroid patient. Excessive LT4 treatment in patients of high age is associated with an increased mortality. CONCLUSION: Suboptimal and excessive LT4 replacement of the preventable non-communicable disease hypothyroidism requires more focus from the healthcare system and from the global political systems to prevent the personally devastating and socioeconomically challenging consequences.

Indicators of Suboptimal Treatment and Associated Healthcare Costs Among Patients With Crohn's Disease Initiated on Biologic or Conventional Agents.

Background: As the treatment landscape for Crohn's disease (CD) evolves, an up-to-date understanding of the burden associated with indicators of suboptimal treatment is needed. The aim of this study was to describe suboptimal treatment indicators and associated healthcare costs among CD patients initiated on a biologic or conventional agent. Methods: Adults with CD were identified in a US healthcare claims database (Optum's Clinformatics Data Mart; 01/2004-03/2019). The first biologic or conventional agent claim within 12 months of a CD diagnosis was the index date/agent. Indicators of suboptimal treatment (nonadherence, dose escalation, chronic corticosteroid use, augmentation, ≥1 CD surgery, ≥2 CD emergency department visits, ≥1 CD inpatient (IP) stay, switch, cycling, restart, inadequate induction) were identified in the 12-month postindex landmark period. The mean per-patient-per-year (PPPY) healthcare costs (2019 USD) were evaluated in the year postlandmark. Results: There were 5107 patients (mean age ~44 years, 56% female) in the biologic and 6072 patients (~51 years; 59% female) in the conventional cohort. In the biologic cohort, 79.4% of patients had ≥1 suboptimal treatment indicator. Mean PPPY healthcare costs increased with the number of suboptimal treatment indicators, from $46 100 (no indicator) to $68 572 (≥4 indicators). The conventional cohort had similar patterns: 72.5% of patients presented ≥1 suboptimal treatment indicator, and mean PPPY healthcare costs increased from $17 329 (no indicator) to $67 568 (≥4 indicators). In both cohorts, IP and outpatient medical costs (excluding biologics) contributed a major portion of the increase. Conclusions: Among CD patients, suboptimal treatment indicators were common and were associated with an increased burden to the healthcare system.

Increasing Mortality in Korean Patients With Breast Cancer: High Mortality Rate in Elderly Breast Cancer Population Due to Suboptimal Treatment and Other Diseases.

BACKGROUND: The incidence of breast cancer in Asia, including Korea, has rapidly increased. Each country has shown different clinical features. This study presents a comprehensive understanding of breast cancer in different age groups in Korea and determines potential measures for improving patient survival. METHODS: Patients diagnosed with invasive breast cancer stages I to III with available clinicopathologic and follow-up data were included in the study. Kaplan-Meier survival graphs were generated for each group and compared using log-rank test. The hazard ratio for each risk factor was calculated using the Cox regression model and the 95% confidence interval. RESULTS: The final cohort included 833 patients with a mean age of 51.3±11.3 years (range, 22-89 years), and 191 (22.9%) of them were aged >60 years. Patients aged ≥60 years had worse overall survival (OS) and distant disease-free survival than those aged <60 years. Although no difference was observed in the tumor biology, elderly patients showed significant differences in practice patterns: they tended to undergo mastectomy (40.2% vs 62.8%, P<0.001), did not receive the standard chemotherapy (88.4% vs 69.3%, P < 0.001), and had a higher risk of developing second primary cancer or diseases other than breast cancer (1.2% vs 6.8%, P < 0.001), which significantly correlated with poor survival in elderly patients. CONCLUSION: Less-than-the-standard treatment of care or development of a second primary disease resulted in poor prognosis in elderly patients in Korea. A multi-institutional and multinational study is warranted to elucidate the clinical features of breast cancer in Asian patients.

Challenges of Misdiagnosis and Suboptimal Treatment of Persistent Idiopathic Facial Pain and Atypical Odontalgia: A Retrospective Multi-Centric Cross-Sectional Investigation.

PURPOSE: To explore the challenges faced in the diagnosis and treatment of atypical odontalgia (AO) and other persistent idiopathic facial pain (PIFP). PATIENTS AND METHODS: This retrospective multi-centric cross-sectional study utilized clinical information (eg, clinical manifestations, history of consultations and treatments prior to correct diagnoses) from patients' medical records. Their economic parameters were also extracted from medical insurance databases. Each variable collected was statistically analyzed. Differences of variables between AO and other PIFP were statistically tested. RESULTS: A total of 394 patients were included in this study. On average, the diagnostic delay was 34.8±14.2 months, a median of 7 consultations were performed prior to a correct diagnosis, and 5 ineffective prescriptions were issued. Patients with AO suffered from longer diagnostic delays than patients with other PIFP (38.4±14.3 months vs 31.6±13.4 months) and were more likely to receive invasive dental treatments (73.3% vs 4.3%). The median total cost of treatment for a single patient before correct diagnosis was 8506.3 yuan. Patients with AO spent more than patients with other PIFP (10,146.5 Yuan vs 3864.0 Yuan). CONCLUSION: Patients with PIFP were frequently misdiagnosed and the length of diagnostic delay was observed to be long. Ineffective medications, unwarranted procedures, and unnecessary economic burden were imposed on the patients. Patients with AO are in a worse situation than patients with other PIFP. As significantly urgent and unsatisfactory results of misdiagnosis of PIFP have been reported in our study, more attention should be paid on the research and education in this field.

Mixed-phenotype acute leukemia: suboptimal treatment when the 2008/2016 WHO classification is used.

BACKGROUND: Different criteria have been used to diagnose mixed-phenotype acute leukemia (MPAL), which has impacted the number of individuals diagnosed with this pathology. Better outcomes have been reported when using acute lymphoblastic leukemia (ALL)-type chemotherapy in the treatment of MPAL. METHODS: We compared the outcome of 4 groups of patients with MPAL. Group 1 included patients diagnosed using the 2008/2016 World Health Organization (WHO) classification; group 2 included patients diagnosed using the European Group for the Immunological Characterization of Leukemias (EGIL) criteria; group 3 included patients diagnosed using either the EGIL or the 2008/2016 WHO criteria; and group 4 was comprised of patients diagnosed with MPAL using the EGIL classification only. RESULTS: We found a significantly worse disease-free survival (groups 1-4) and overall survival (OS) (groups 2 and 3) when comparing MPAL patients to other acute leukemia (AL) patients. A significantly better OS was obtained in patients (groups 2-4) treated with ALL-type chemotherapy compared to acute myeloid leukemia (AML)-type regimens. CONCLUSION: In light of these results, and because a trend (P=0.06) was found with regard to a better OS in group 4 when compared to other AL patients, an argument can be made that the 2008/2016 WHO classification is underpowered to diagnose all MPAL cases, potentially resulting in the suboptimal treatment of some individuals with AL.

Mixed-phenotype acute leukemia: suboptimal treatment when the 2008/2016 WHO classification is used

BACKGROUND: Different criteria have been used to diagnose mixed-phenotype acute leukemia (MPAL), which has impacted the number of individuals diagnosed with this pathology. Better outcomes have been reported when using acute lymphoblastic leukemia (ALL)-type chemotherapy in the treatment of MPAL. METHODS: We compared the outcome of 4 groups of patients with MPAL. Group 1 included patients diagnosed using the 2008/2016 World Health Organization (WHO) classification; group 2 included patients diagnosed using the European Group for the Immunological Characterization of Leukemias (EGIL) criteria; group 3 included patients diagnosed using either the EGIL or the 2008/2016 WHO criteria; and group 4 was comprised of patients diagnosed with MPAL using the EGIL classification only. RESULTS: We found a significantly worse disease-free survival (groups 1-4) and overall survival (OS) (groups 2 and 3) when comparing MPAL patients to other acute leukemia (AL) patients. A significantly better OS was obtained in patients (groups 2-4) treated with ALL-type chemotherapy compared to acute myeloid leukemia (AML)-type regimens. CONCLUSION: In light of these results, and because a trend (P=0.06) was found with regard to a better OS in group 4 when compared to other AL patients, an argument can be made that the 2008/2016 WHO classification is underpowered to diagnose all MPAL cases, potentially resulting in the suboptimal treatment of some individuals with AL.

How Effective is the Treatment of Locally Advanced and Metastatic Breast Cancer in Developing Centres?: A Retrospective Review.

BACKGROUND: The use of chemotherapy in advanced metastatic breast cancer remains a subject of controversy. The thought of MicKinnon et al (early 1950s) that the course of breast cancer was unaffected by chemotherapy has been refuted by results of treatment in the developed countries. The poor result of treatment in developing centres still compares with prechemotherapy era. Consequently, The McKinnon's thought may still lurk. We compared the survival of chemotherapy treated with chemotherapy untreated cancer of breast patients. METHOD: Records of breast cancer patients who presented and died between January 2010 and May 2014 were reviewed. The primary outcome was overall survival. Records of patients that received chemotherapy with or without other tumor directed specific therapy were compared with records of patients who did not receive any tumor directed therapy. RESULT: Thirty-one patients received chemotherapy while 25 patients did not. All were females, more than 90% were of the patients had advanced or metastatic disease. Treatments were not biologically directed and treatment plans were largely compromised and suboptimal. The overall mean survival was 19.2 ±9.2 months, and the median duration was 17.5 months(range 6-44months). The overall survival was not statistically different between the two groups (p= 0.230, unequal variance assumed). The objective of using neoadjuvant chemotherapy for fungating lesions was not achieved. CONCLUSION: In advanced and metastatic breast cancer, outcomes of patients who receive suboptimal regimen of cytotoxic chemotherapy do not differ from chemotherapy untreated patients.

Reconceiving the therapeutic obligation.

The "therapeutic obligation" (TO) is a physician's duty to provide his patients with what he believes is the best available treatment. We begin by discussing some prominent formulations of the obligation before raising two related considerations against those formulations. First, they do not make sense of cases where doctors are permitted to provide suboptimal care. Second, they give incorrect results in cases where doctors are choosing treatments in challenging epistemic environments. We then propose and defend an account of the therapeutic obligation that solves the problems that undermined previous efforts at formulating the TO. We conclude by considering how apparent problems with our proposal actually rest on difficulties with informed consent.