Real-World Evidence in the Reassessment of Oncology Therapies: Payer Perceptions From Five Countries - Supplementary Material

Supplemental Table. Committees Advancing Real-World Evidence for Decision Making</p

The economic burden of common adverse events associated with metastatic colorectal cancer treatment in the United States

<p><b>Aims:</b> Adverse events (AEs) associated with treatments for metastatic colorectal cancer (mCRC) may compromise the course of treatment, impact quality-of-life, and increase healthcare resource utilization. This study assessed the direct healthcare costs of common AEs among mCRC patients in the US.</p> <p><b>Methods:</b> Adult mCRC patients treated with chemotherapy or targeted therapies were identified from administrative claims databases (2009–2014). Up to the first three mCRC treatment episodes per patient were considered and categorized as with or without the AE system/organ category during the episode. Total healthcare costs (2014 USD) were measured by treatment episode and reported on a monthly basis. Treatment episodes with the AE category were matched by treatment type and line of treatment to those without the AE category. Adjusted total cost differences were estimated by comparing costs during treatment episodes with vs without the AE category using multivariate regression models; <i>p</i>-values were estimated with bootstrap.</p> <p><b>Results:</b> A total of 4158 patients with ≥1 mCRC treatment episode were included (mean age = 59 years; 58% male; 60% with liver and 14% with lung metastases; 2,261 [54%] with a second and 1,115 [27%] with a third episode). On average, two treatment episodes were observed per patient with an average length of 166 days per episode. Adjusted monthly total cost difference by AE category included hematologic ($1,480), respiratory ($1,253), endocrine/metabolic ($1,213), central nervous system (CNS;$1,136), and cardiovascular ($1,036; all <i>p</i> < .05).</p> <p><b>Limitations:</b> Claims do not include information on the cause of AEs, and potentially less severe AEs may not have been reported by the physician when billing the medical service. This study aimed to assess the association between costs and AEs and not the causation of AEs by treatment.</p> <p><b>Conclusions:</b> The most costly AEs among mCRC patients were hematologic, followed by respiratory, endocrine/metabolic, CNS, and cardiovascular.</p

Proximal Arterial Occlusion in Acute Ischemic Stroke with Low NIHSS Scores Should Not Be Considered as Mild Stroke

<div><p>Background</p><p>Untreated acute mild stroke patients have substantial 90-day disability rates and worse outcomes than those who are treated with thrombolysis. There is little information regarding which patients with acute mild stroke will benefit from thrombolysis. We sought to investigate factors that are associated with early neurological deterioration (END) and poor prognosis in patients with acute mild stroke.</p><p>Methods</p><p>This was a retrospective study of consecutively registered patients with acute mild stroke (NIHSS ≤3) at our tertiary stroke center between October 2008 and December 2011. END was defined as an increase in NIHSS ≥2 points between hospital days 0 and 5. Modified Rankin Scale (mRS) scores of 0–1 at 90 days post-stroke were defined as favorable outcomes.</p><p>Results</p><p>A total of 378 (mean age, 65.9±13.0 years) patients were included in this study. END occurred in 55 patients (14.6%). IV-thrombolysis was performed in only 9 patients. Symptomatic arterial occlusion on the initial MRA was independently associated with END (OR, 2.206; 95% CI, 1.219–3.994; <i>p</i> = 0.009) by multivariate logistic regression. Of the 119 patients with symptomatic arterial occlusion, ICA occlusion was independently associated with END (OR, 8.606; 95% CI, 2.312–32.043; <i>p</i> = 0.001).</p><p>Conclusions</p><p>This study demonstrates that symptomatic arterial occlusion may be an important predictor of END in patients with acute mild stroke. It may therefore be important to consider that acute ischemic stroke with symptomatic arterial occlusion and low NIHSS scores may not represent mild stroke in acute periods.</p></div

Use of Antithrombotics after Hemorrhagic Transformation in Acute Ischemic Stroke

<div><p>Backgrounds</p><p>There have been neither appropriate guidelines nor clinical studies about the use of antithrombotics after hemorrhagic transformation (HT). We sought to find whether the use of antithrombotics after hemorrhagic infarction might be associated with aggravation of HT and neurological deterioration.</p><p>Methods</p><p>This retrospective study included prospectively registered consecutive patients with acute ischemic stroke and HT in our tertiary stroke center. We focused on the hemorrhagic infarction. Aggravation of HT was defined as either enlargement of the original HT or newly developed HT within the infarcted area by visual analysis. We analyzed relationships between antithrombotics and HT, and neurological deterioration after HT in patients with hemorrhagic infarction. In addition, we assessed composite outcomes including neurological deterioration, vascular events, and death at 1month after HT. We analyzed relationships between antithrombotics after discharge and composite outcomes within 1month after HT.</p><p>Results</p><p>222 patients were finally analyzed. Of the 150 patients with hemorrhagic infarction, 75 (50.0%) were type 1. The use of warfarin after detection of hemorrhagic infarction more frequently increased aggravation of HT than did the use of antiplatelets (4 of 24 vs 3 of 69; <i>p</i> = 0.094), but neither warfarin nor antiplatelets caused more HT than no medication. In addition, the use of antithrombotics after hemorrhagic infarction was not significantly associated with neurological deterioration after HT. The frequency of composite events at 1months was significantly lower in patients treated with antithrombotics than those treated without (<i>p</i> = 0.041).</p><p>Conclusion</p><p>In conclusion, the results of this study suggest that antithrombotics can safely be used after hemorrhagic infarction and may not be associated with neurological deterioration and aggravation of HT. Further studies are needed to confirm our results.</p></div

Types of hemorrhagic infarction based on thrombolysis and clinical and imaging changes associated with use of antithrombotics.

<p>HT, hemorrhagic transformation; ND, neurological deterioration.</p

General characteristics of subjects.

<p>Baseline NIHSS scores, onset to visit time, and initial blood glucose levels were analyzed using the Mann-Whitney <i>U</i> test after tests of normality.</p><p>END, early neurological deterioration; TOAST, Trial of Org 10172 in Acute Stroke Treatment; LAA, large artery atherosclerosis; CE, cardioembolism; SVO, small vessel occlusion; UD, undetermined; NIHSS, National Institutes of Health Stroke Scale; PAI, perforating artery infarcts; PI, pial infarcts; BI, border zone infarcts; TI, territorial infarcts; LI, lacunar infarcts; IVT, intra-venous thrombolysis; IAR, intra-arterial revascularization.</p>*<p>Lesion patterns were analyzed only in patients with lesions in anterior circulation.</p

In hemorrhagic infarction (N = 150), a comparison of the development of HT aggravation (A) and neurological deterioration after HT (B) associated with the use of anti-thrombotic medication after HT.

<p>Abbreviations: HI, hemorrhagic infarction; HT, hemorrhagic transformation; ND, neurological deterioration after HT; END, early neurological deterioration.</p

The associations between use of antithrombotics with ND after HT by multivariate logistic regression analysis in patients with hemorrhagic infarction (N = 150).

<p>Model 1: Adjusted by age and initial NIHSS. Model 2: Adjusted by age, initial NIHSS, and thrombolysis.</p

The distribution of occlusion sites according to END type.

<p><b>MCA and ICA occlusions contributed most frequently to severe END.</b> (Abbreviation: MCAO, middle cerebral artery occlusion; ICAO, internal carotid artery occlusion; VBAO, vertebrobasilar artery occlusion; otherAO, other arterial occlusion; no RAO, no relevant arterial occlusion).</p

The distribution of various types of END and mRS scores of 0–1 and 0–2 at 90 days in terms of baseline NIHSS scores (^*<i>p</i> for trends <0.05).

<p>The distribution of various types of END and mRS scores of 0–1 and 0–2 at 90 days in terms of baseline NIHSS scores (^*<i>p</i> for trends <0.05).</p