Impact of value frameworks on the magnitude of clinical benefit: Evaluating a decade of randomized trials for systemic therapy in solid malignancies.

e19410 Background: In the era of rapid development of new, expensive cancer therapies, value frameworks were developed to quantify clinical benefit. We assessed the evolution of the magnitude of clinical benefit since the 2015 introduction of the ASCO and ESMO value frameworks. Methods: Randomized phase II and III clinical trials assessing systemic therapies for solid malignancies from January 2010 to July 2019 were evaluated. Study characteristics were recorded, and magnitude of clinical benefit (Δ) was calculated for the endpoints overall survival (OS), progression-free survival (PFS), response rate (RR), and quality of life (QoL). Multivariable analyses compared ΔOS, ΔPFS, and ΔRR in 2010-2014 [pre-value frameworks (PRE)] to 2015-2019 [post-value frameworks (POST)]. Results: In the 290 studies analyzed [60 (21%) PRE and 230 (79%) POST], the most common primary endpoint was PFS (46%), followed by OS (20%), RR (16%), and QoL (8%), with a non-significant increase in OS and decrease in RR as a primary endpoint in the POST era (Table). Studies evaluating immunotherapy and palliative therapy significantly increased POST [0 (0%) v 39 (17%), Fisher’s exact p<0.01 and 25 (42%) v 142 (62%), Chi squared p=0.01, respectively]. Studies reporting improvement in QoL doubled POST [3 (5%) v 22 (10%) Fisher’s exact p=0.56], however not statistically significant. Median ΔOS was significantly greater POST (N= 140 evaluable studies, 1.3 v -0.2 months, Wilcoxon p=0.005) but there was no significant difference in median ΔPFS or ΔRR. Multivariable analyses revealed significant improvement in ΔOS POST (OR 3.08, 95% CI 0.54-5.62, p=0.02) while adjusting for drug mechanism of action, line of therapy, disease setting, and primary endpoint. Conclusions: After the development of value frameworks, median OS improved minimally. The impact of value frameworks has yet to be fully realized in randomized clinical trials. Efforts to include endpoints shown to impact value, such as QoL, into clinical trials are warranted. [Table: see text]

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Impact of Value Frameworks on the Magnitude of Clinical Benefit: Evaluating a Decade of Randomized Trials for Systemic Therapy in Solid Malignancies

Current Oncology ◽

10.3390/curroncol28060412 ◽

2021 ◽

Vol 28 (6) ◽

pp. 4894-4928

Author(s):

Ellen Cusano ◽

Chelsea Wong ◽

Eddy Taguedong ◽

Marcus Vaska ◽

Tasnima Abedin ◽

...

Keyword(s):

Clinical Trials ◽

Clinical Benefit ◽

Randomized Clinical Trials ◽

Rapid Development ◽

Progression Free Survival ◽

Cancer Therapies ◽

Primary Endpoints ◽

Solid Malignancies ◽

American Society ◽

The Impact

In the era of rapid development of new, expensive cancer therapies, value frameworks have been developed to quantify clinical benefit (CB). We assessed the evolution of CB since the 2015 introduction of The American Society of Clinical Oncology and The European Society of Medical Oncology value frameworks. Randomized clinical trials (RCTs) assessing systemic therapies for solid malignancies from 2010 to 2020 were evaluated and CB (Δ) in 2010–2014 (pre-value frameworks (PRE)) were compared to 2015–2020 (POST) for overall survival (OS), progression-free survival (PFS), response rate (RR), and quality of life (QoL). In the 485 studies analyzed (12% PRE and 88% POST), the most common primary endpoint was PFS (49%), followed by OS (20%), RR (12%), and QoL (6%), with a significant increase in OS and decrease in RR as primary endpoints in the POST era (p = 0.011). Multivariable analyses revealed significant improvement in ΔOS POST (OR 2.86, 95% CI 0.46 to 5.26, p = 0.02) while controlling for other variables. After the development of value frameworks, median ΔOS improved minimally. The impact of value frameworks has yet to be fully realized in RCTs. Efforts to include endpoints shown to impact value, such as QoL, into clinical trials are warranted.

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A Survey of Marine Coastal Litters around Zhoushan Island, China and Their Impacts

Journal of Marine Science and Engineering ◽

10.3390/jmse9020183 ◽

2021 ◽

Vol 9 (2) ◽

pp. 183

Author(s):

Xuehua Ma ◽

Yi Zhou ◽

Luyi Yang ◽

Jianfeng Tong

Keyword(s):

Rapid Development ◽

Univariate Analysis ◽

Local Environment ◽

Marine Litter ◽

Social Ecological ◽

The Social ◽

Significant Difference ◽

Valuable Method ◽

Beach Litter ◽

The Impact

Rapid development of the economy increased marine litter around Zhoushan Island. Social-ecological scenario studies can help to develop strategies to adapt to such change. To investigate the present situation of marine litter pollution, a stratified random sampling (StRS) method was applied to survey the distribution of marine coastal litters around Zhoushan Island. A univariate analysis of variance was conducted to access the amount of litter in different landforms that include mudflats, artificial and rocky beaches. In addition, two questionnaires were designed for local fishermen and tourists to provide social scenarios. The results showed that the distribution of litter in different landforms was significantly different, while the distribution of litter in different sampling points had no significant difference. The StRS survey showed to be a valuable method for giving a relative overview of beach litter around Zhoushan Island with less effort in a future survey. The questionnaire feedbacks helped to understand the source of marine litter and showed the impact on the local environment and economy. Based on the social-ecological scenarios, governance recommendations were provided in this paper.

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Abstract 14873: Is There Difference in Clinical Outcomes Following Percutaneous Coronary Intervention (PCI) for Acute Coronary Syndrome (ACS) between Hospitals With and Without Onsite Cardiac Surgery Backup?

Circulation ◽

10.1161/circ.130.suppl_2.14873 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Tomonori Akasaka ◽

Seiji Hokimoto ◽

Noriaki Tabata ◽

Kenji Sakamoto ◽

Kenichi Tsujita ◽

...

Keyword(s):

Cardiac Surgery ◽

Clinical Outcomes ◽

Primary Endpoint ◽

Proportional Hazards Model ◽

Cox Proportional Hazards Model ◽

Bleeding Complications ◽

Hospital Death ◽

Coronary Syndrome ◽

Significant Difference ◽

The Impact

Background: Based on 2011 ACCF/AHA/SCAI PCI guideline, it is recommended that PCI should be performed at hospital with onsite cardiac surgery. But, recent data suggests that there is no significant difference in clinical outcomes following primary or elective PCI between hospitals with and without onsite cardiac surgery. The proportion of PCI centers without onsite cardiac surgery comprises approximately more than half of all PCI centers in Japan. We examined the impact of with or without onsite cardiac surgery on clinical outcomes following PCI to ACS. Methods: From Aug 2008 to March 2011, subjects (n=2288) were enrolled from the Kumamoto Intervention Conference Study (KICS), which is a multicenter registry, and enrolling consecutive patients undergoing PCI in 15 centers in Japan. Patients were assigned to two groups treated in hospitals with (n=1954) or without (n=334) onsite cardiac surgery. Clinical events were followed up for 12 months. Primary endpoint was in-hospital death, cardiovascular death, myocardial infarction, and stroke. And we monitored other events those were non-cardiovascular deaths, bleeding complications, revascularizations, and emergent CABG. Results: There was no overall significant difference in primary endpoint between hospitals with and without onsite cardiac surgery (9.6%vs9.5%; P=0.737). There was also no significant difference when events in primary endpoint were considered separately. In other events, only revascularization was more frequently seen in hospitals with onsite cardiac surgery (22.1%vs12.9%; P<0.001). Kaplan-Meier analysis for primary endpoint showed that there was no significant difference between two groups (Log Rank P=0.943). By cox proportional hazards model analysis for primary endpoint, without onsite cardiac surgery was not a predictive factor for primary endpoint (HR 0.969, 95%CI 0.704-1.333; P=0.845). We performed propensity score matching analysis to correct for the disparate patient numbers between two groups, and there was also no significant difference for primary endpoint (6.9% vs 8.0%; P=0.544). Conclusions: There is no significant difference in clinical outcomes following PCI for ACS between hospitals with and without onsite cardiac surgery backup in Japan.

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Improved clinical symptoms and mortality among patients with severe or critical COVID-19 after convalescent plasma transfusion

Blood ◽

10.1182/blood.2020007079 ◽

2020 ◽

Vol 136 (6) ◽

pp. 755-759 ◽

Cited By ~ 22

Author(s):

Xinyi Xia ◽

Kening Li ◽

Lingxiang Wu ◽

Zhihua Wang ◽

Mengyan Zhu ◽

...

Keyword(s):

Clinical Trials ◽

Clinical Benefit ◽

Clinical Symptoms ◽

Case Series ◽

Plasma Transfusion ◽

Controlled Clinical Trials ◽

Early Administration ◽

The Impact

Two case series examining the impact of convalescent plasma on patients with COVID-19 suggest some clinical benefit from early administration and modest impact on parameters of inflammation. Further assessment of the impact of this intervention awaits controlled clinical trials.

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Perioperative rifaximin is not associated with enhanced functional and volumetric recovery after major liver resection

Scientific Reports ◽

10.1038/s41598-021-97442-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jan Bednarsch ◽

Zoltan Czigany ◽

Sven H. Loosen ◽

Lara Heij ◽

Lorenz Ruckgaber ◽

...

Keyword(s):

Liver Function ◽

Primary Endpoint ◽

Major Hepatectomy ◽

Controlled Trial ◽

Liver Volume ◽

Relative Increase ◽

Control Group ◽

Open Label ◽

Significant Difference ◽

The Impact

AbstractThe objective of this randomized controlled trial (RCT) was to assess the impact of rifaximin on the course of liver function, liver regeneration and volumetric recovery in patients undergoing major hepatectomy. The ARROW trial was an investigator initiated, single-center, open-label, phase 3 RCT with two parallel treatment groups, conducted at our hepatobiliary center from 03/2016 to 07/2020. Patients undergoing major hepatectomy were eligible and randomly assigned 1:1 to receive oral rifaximin (550 mg twice daily for 7–10 or 14–21 days in case of portal vein embolization preoperatively and 7 days postoperatively) versus no intervention. Primary endpoint was the relative increase in postoperative liver function measured by LiMAx from postoperative day (POD) 4 to 7. Secondary endpoint were the course of liver function and liver volume during the study period as well as postoperative morbidity and mortality. Between 2016 and 2020, 45 patients were randomized and 35 patients (16 individuals in the rifaximin and 19 individuals in the control group) were eligible for per-protocol analysis. The study was prematurely terminated following interim analysis, due to the unlikelihood of reaching a significant primary endpoint. The median relative increase in liver function from POD 4 to POD 7 was 27% in the rifaximin group and 41% in the control group (p = 0.399). Further, no significant difference was found in terms of any other endpoints of functional liver- and volume regeneration or perioperative surgical complications following the application of rifaximin versus no intervention. Perioperative application of rifaximin has no effect on functional or volumetric regeneration after major hepatectomy (NCT02555293; EudraCT 2013-004644-28).

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Impact of concomitant medication use and immune-related adverse events on response to immune checkpoint inhibitors

Immunotherapy ◽

10.2217/imt-2019-0064 ◽

2020 ◽

Vol 12 (2) ◽

pp. 141-149 ◽

Cited By ~ 5

Author(s):

Shipra Gandhi ◽

Manu Pandey ◽

Nischala Ammannagari ◽

Chong Wang ◽

Mark J Bucsek ◽

...

Keyword(s):

Adverse Events ◽

Clinical Benefit ◽

Immune Checkpoint Inhibitors ◽

Concomitant Medication ◽

Checkpoint Inhibitors ◽

Metastatic Cancer ◽

Medication Use ◽

Significant Difference ◽

Β Blockers ◽

The Impact

Aim: Patients receiving checkpoint inhibitors (CPI) are frequently on other medications for co-morbidities. We explored the impact of concomitant medication use on outcomes. Materials & methods: 210 metastatic cancer patients on CPI were identified and association between concomitant medication use and immune-related adverse events with clinical outcomes was determined. Results: Aspirin, metformin, β-blockers and statins were not shown to have any statistically significant difference on clinical benefit. 26.3% patients with clinical benefit developed rash versus 11.8% without clinical benefit (p < 0.05) on multivariate analysis. Conclusion: Use of common prescription and nonprescription medications in patients with multiple co-morbidities appears safe and does not have an adverse effect on CPI efficacy. The presence of rash predicted for a better response.

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Acupuncture Treatments for Post-stroke Depression: A Systematic Review and Network Meta-analysis

10.21203/rs.3.rs-951353/v1 ◽

2021 ◽

Author(s):

Lam Wai Ching ◽

Hui Juan Li ◽

Jianwen Guo ◽

Liang Yao ◽

Janita Chau ◽

...

Keyword(s):

Clinical Trials ◽

Randomized Clinical Trials ◽

Rating Scale ◽

Meta Analysis ◽

Cochrane Library ◽

Depression Symptoms ◽

Post Stroke ◽

Significant Difference ◽

Post Stroke Depression ◽

The Impact

Abstract Background: Depression is one of the most common complications after stroke, with a prevalence of 30-33%. Patients with post-stroke depression (PSD) usually experience anxiety, hopelessness, and insomnia, which have a negative impact on their daily activities and post-stroke rehabilitation. In this review, we aimed to explore the impact of acupuncture in alleviating symptoms of PSD and to evaluate the difference in effectiveness between acupuncture combined with pharmacotherapies and various non-pharmacotherapies in order to provide guides and advice for clinical personnel. Methods: Six databases (Cochrane Library, PubMed, EMBASE, China National Knowledge Infrastructure, Wanfang Database, Chongqing VIP Database) and two clinical trials registration platforms were searched from inception to May 2021. Randomized clinical trials (RCTs) comparing needle-based acupuncture with pharmacotherapy, and other non-pharmacotherapy or invalid group were included. Two independent reviewers identified eligible studies. Two reviewers independently abstracted and recorded data into a pre-made form. A Bayesian network meta-analysis (NMA) was conducted to assess and compare different techniques using RStudio 3.6.0. The primary outcome was the change in scores of scales measuring depressive symptoms. The secondary outcomes were changes in serotonin levels and in quality of life. Results: Fifty-nine RCTs were included. The results of this NMA showed that compared with western medicine (WM), acupuncture alone or with repetitive transcranial magnetic stimulation (RTMS), Traditional Chinese medicine (TCM) alone or with WM, were superior for alleviating depression symptoms. Compared to Usual Care, acupuncture alone or plus other therapies could significantly decrease scores of the Hamilton Depression Rating scale. However, there was no significant difference found among acupuncture, WM, TCM with AC plus any of other treatment.Conclusions: The results of this study indicate that acupuncture alone or combined with other therapies appear to be effective in improving depression symptoms of stroke survivors. Moreover, in comparison with WM, acupuncture alone or plus RTMS, TCM, TCM with WM, or WM, were more effective in improving depression symptoms. Also, acupuncture with RTMS seems to be the most effective with the highest probability.

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The impact of catheter ablation for patients with asymptomatic atrial fibrillation: subanalysis of kansai plus atrial fibrillation (kpaf) registry

European Heart Journal ◽

10.1093/ehjci/ehaa946.0442 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

M Pak ◽

A Kobori ◽

S Shizuta ◽

Y Sasaki ◽

T Toyota ◽

...

Keyword(s):

Atrial Fibrillation ◽

Catheter Ablation ◽

Primary Endpoint ◽

Hazard Analysis ◽

Secondary Endpoint ◽

Asymptomatic Patients ◽

Significant Difference ◽

Secondary Endpoints ◽

The Impact

Abstract Background Catheter ablation (CA) of atrial fibrillation (AF) for symptomatic patients improves the quality of life and prognosis of patients with heart failure. However, the impact of CA for asymptomatic patients is still controversial. Purpose We aimed to investigate the clinical outcomes of CA of AF for asymptomatic patients compared to those for symptomatic patients. Methods A total of 5,013 patients from the Kansai Plus Atrial Fibrillation (KPAF) Registry who underwent CA were screened. The patients were divided into three groups by type of AF; paroxysmal (PAF), persistent (PEAF) and long standing (LSAF) and the patients in each type of AF were divided into two groups: asymptomatic and symptomatic. The primary endpoint was recurrent supraventricular tachyarrhythmias lasting for more than 30 seconds during follow-up 4 years after CA. The secondary endpoint was a composite of cardiovascular, cerebral, and gastrointestinal events during follow-up 4 years after CA. The incidence of complications related to CA between asymptomatic and symptomatic patients was also evaluated. Kaplan–Meier analysis was employed to estimate the primary and secondary endpoints. The statistical differences in primary and secondary endpoints between asymptomatic and symptomatic patients were evaluated using a log–rank test. The impact of symptom due to AF on the primary and secondary endpoint was evaluated using a Cox hazard analysis. The difference in incidence of complications between asymptomatic and symptomatic patients was evaluated using a chi–square test. Results In this study population, PAF was the most frequent at 64.4%, followed by PEAF (22.7%) and LSAF (13.0%). There were some significant differences in the baseline characteristics between asymptomatic and symptomatic patients in each type of AF. The proportion of male was significantly higher in asymptomatic patients than symptomatic patients in PAF (81.2% versus 67.2%, p<0.001) and PEAF (86.4% versus 74.3%, p<0.001). Left atrial diameter was larger in asymptomatic patients than symptomatic patients only in PAF (40±6mm versus 38±6mm, p<0.001). In all types of AF, there was no significant difference in primary endpoint between asymptomatic and symptomatic patients as follows: 37.5% versus 40.6% (p=0.6) in PAF, 45.2% versus 55.1% (p=0.09) in PEAF and 59.3% versus 63.6% (p=1.0) in LSAF. There was also no significant difference in secondary endpoint between asymptomatic and symptomatic patients: 7.1% versus 6.8% (p=0.7) in PAF, 5.4% versus 8.7% (p=0.3) in PEAF and 4.4% versus 5.1% (p=0.5) in LSAF. In a Cox hazard analysis, the symptom did not affect both of the primary and secondary endpoints in each type of AF. In regard to the incidence of complications related to CA, there was no significant difference between asymptomatic and symptomatic patients in each type of AF. Conclusion CA of AF for asymptomatic patients can be safe and can lead to equivalent outcomes as well as symptomatic patients. Funding Acknowledgement Type of funding source: None

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Abstract W P299: Impact of an Institutional Guideline on Implementing Early Decompressive Hemicraniectomy (DHC) for Large Middle Cerebral Artery Stroke

Stroke ◽

10.1161/str.46.suppl_1.wp299 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Casey Olm-Shipman ◽

Victoria Marquevich ◽

Jonathan Rosand ◽

Aman Patel ◽

Emad Eskandar ◽

...

Keyword(s):

Clinical Trials ◽

Guideline Implementation ◽

Rapid Identification ◽

Decompressive Hemicraniectomy ◽

Significant Difference ◽

Class 1 ◽

Before And After ◽

The Impact ◽

Mean Time

Background: Recent AHA Acute Stroke Guidelines endorse DHC (Class 1, Level B) based on clinical trials showing benefit of early DHC on outcome and mortality. In 2011, our multidisciplinary quality improvement team developed a process to translate DHC guideline recommendations into clinical practice. Methods: Our consensus guideline includes a tool (STATE Criteria, based on inclusion/exclusion criteria of DHC clinical trials) to rapidly identify and triage potential DHC candidates, and provide specific guidelines for pre- and post-surgical management, adjunctive therapy, and DHC after IV/IA thrombolysis. Patients meeting all STATE Criteria including age ≤ 60 years are sent for urgent DHC. Patients meeting all criteria except age ≤ 60 years receive DHC only if age < 75 years and Neurology and Neurosurgery teams reach consensus about benefit. Patients not meeting criteria are observed and referred for DHC if criteria are met within 48 hours of onset. The guideline was disseminated to all stakeholders via email, conferences, and intranet. In this study, we retrospectively analyzed process and outcome measures for DHC before and after guideline implementation in February 2011. Results: Of 1518 stroke patients age ≤ 60 years admitted between January 2007 and April 2014, 47 (3%) received DHC (22 pre- and 25 post-guideline implementation; 28% female, 13% Hispanic). Mean admission NIHSS was similar (17±7 vs 18±5; p=.82). Mean time from admission to DHC improved significantly from 45±30 hours to 29±18 hours (p=0.04). The percentage of patients undergoing DHC beyond 48 hours decreased from 27% to 16% (p=0 .35). The degree of midline shift evident on CT or MRI prior to DHC significantly decreased from 9±4 mm to 5±4 mm (p=.01). There was no significant difference in length of stay, frequency of tracheostomy, gastrostomy, pneumonia, or urinary tract infection, or percentage of patients who died within 30 days of DHC. Conclusion: Our institutional guideline has facilitated the rapid identification and triage of patients with large MCA stroke to DHC. Follow-up is ongoing to determine the impact of our guideline on functional outcome after stroke.

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The impact of subclinical hyperthyroidism on cardiovascular prognosis in patients undergoing PCI

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab855 ◽

2021 ◽

Author(s):

Jie Yang ◽

Yitian Zheng ◽

Chen Li ◽

Yu Peng Liu ◽

Qing Zhou ◽

...

Keyword(s):

Primary Endpoint ◽

Cardiovascular Events ◽

Cox Regression ◽

Coronary Intervention ◽

Major Adverse Cardiovascular Events ◽

Drug Eluting Stent ◽

Cox Regression Analysis ◽

Target Vessel Revascularization ◽

Significant Difference ◽

The Impact

Abstract Background Limited studies have focused on the impact of SHyper on poor prognosis in patients with known coronary artery disease (CAD). Hence, we implemented the present study to explore the association between SHyper and adverse cardiovascular events in CAD patients who underwent drug-eluting stent (DES) implantation. Methods We consecutively recruited 8,283 CAD patients undergoing percutaneous coronary intervention (PCI). All subjects were divided into 2 groups according to their thyroid function: group 1 (euthyroidism group, n = 7,942) and group 2 (SHyper group, n = 341). After 1:4 propensity score (PS) matching, 1,603 patients (332 SHyper group and 1,271 euthyroidism group) were selected. The primary endpoint was major adverse cardiovascular events (MACE), a composite of cardiac mortality, nonfatal myocardial infarction (MI), and target vessel revascularization (TVR). Results Kaplan-Meier (K-M) survival analyses suggested that there was no significant difference in the primary endpoint and secondary endpoints (MACE: 11.4% vs. 8.8%, log-rank P = 0.124; cardiac death: 1.2% vs. 0.9%, log-rank P = 0.540; nonfatal MI: 5.7% vs. 4%, log-rank P = 0.177; and TVR: 6% vs. 4.7%, log-rank P = 0.303) in the PS-matched population. Besides, Cox regression analysis indicated that SHyper was not an independent risk factor for MACE (HR: 1.33, 95% CI, 0.92–1.92, P = 0.127). Conclusion SHyper is not independently associated with adverse cardiovascular events in CAD patients undergoing PCI. More studies should be implemented in the future to assess the long-term predictive value of SHyper with thyrotropin (TSH) levels < 0.1 mIU/L for CAD patients undergoing PCI.

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