Validation of a Musculoskeletal Digital Assessment Routing Tool (DART): Protocol for a Pilot Randomised Crossover Non-Inferiority Trial (Preprint)

2021 ◽  
Author(s):  
Cabella Lowe ◽  
Harry Hanuman Sing ◽  
William Marsh ◽  
Dylan Morrissey
Keyword(s):  
Clinical Trials ◽  
Data Collection ◽  
Real World ◽  
User Satisfaction ◽  
Allocation Concealment ◽  
Trial Methodology ◽  
Primary Analysis ◽  
Digital Assessment ◽  
System Usability Scale ◽  
The Impact

BACKGROUND Musculoskeletal conditions account for 16% of global disability, resulting in a negative effect on millions of patients and an increasing burden on healthcare utilization. Digital technologies to improve health care outcomes and efficiency are considered a priority; however, innovations are rarely tested with sufficient rigor in clinical trials, the gold standard for clinical proof of safety and efficacy. We have developed a new musculoskeletal Digital Assessment Routing Tool (DART) that allows users to self-assess and be directed to the right care. DART requires validation in a real-world setting prior to implementation. OBJECTIVE This pilot study will assess the feasibility of a future trial by exploring key aspects of trial methodology, assess the procedures and collect exploratory data to inform the design of a definitive, randomized, crossover, non-inferiority trial to assess DART safety and effectiveness. METHODS We will collect data from 76 adult participants presenting to an NHS England GP practice with a musculoskeletal condition. Participants will complete both a DART assessment and a physiotherapist-led triage with the order determined by randomization. The primary analysis will involve an absolute agreement ICC (A,1) estimate with 95% confidence intervals between DART and the clinician for assessment outcomes sign-posting to condition management pathways. Data will be collected to allow analysis of participant recruitment and retention, randomization, allocation concealment, blinding, data collection process and bias. In addition, the impact of trial burden and potential barriers to intervention delivery will be considered. DART user satisfaction will be measured using the System Usability Scale. RESULTS A UK NHS ethics submission will be submitted during June 2021 and pending approval, recruitment will commence during August 2021 with data collection anticipated to last for 3 months. Results will be reported in a follow-up paper later in 2021. CONCLUSIONS This study will inform the design of a randomized controlled crossover non-inferiority study that will provide evidence concerning mHealth DART system clinical sign posting in an NHS setting prior to real-world implementation. Success should produce evidence of a safe, effective system with excellent usability, facilitating quicker and easier patient access to appropriate care while reducing the burden on primary and secondary care musculoskeletal services. This rigorous approach to mHealth system testing could be used as a guide for other developers of similar applications. CLINICALTRIAL This trial is registered with Clinical Trials number NCT04904029

scholarly journals Usability testing of a Digital Assessment Routing Tool: An Iterative Convergent Mixed Methods Study Protocol (Preprint)

2021 ◽  
Author(s):  
Cabella Lowe ◽  
Harry Hanuman-Sing ◽  
Mitchell Browne ◽  
Meshari F. Alwashmi ◽  
William Marsh ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Mixed Methods ◽  
Data Collection ◽  
Quantitative Data ◽  
Usability Testing ◽  
Manuscript Submission ◽  
Digital Assessment ◽  
Usability Problems ◽  
System Usability Scale ◽  
System Usability

BACKGROUND Musculoskeletal conditions account for 16% of global disability, resulting in a negative effect on millions of patients and an increasing burden on healthcare utilization. Digital technologies to improve health care outcomes and efficiency are considered a priority; however, innovations are often inadequately developed and poorly adopted. Further, they are rarely tested with sufficient rigor in clinical trials, the gold standard for clinical proof of efficacy. We have developed a new musculoskeletal Digital Assessment Routing Tool (DART) that allows users to self-assess and be directed to the right care. DART requires usability testing in preparation for clinical trials. OBJECTIVE This study will use the iterative-convergent mixed methods design to assess and mitigate all serious usability issues to optimize user experience and adoption. This will provide justifiable confidence to progress to full-scale randomized controlled trials when DART is integrated into clinical management pathways. METHODS We will collect qualitative and quantitative data from between 20-30 participants aged 18 and over four months. The exact number of participants recruited will be dependent on the number of iterative cycles required to reach the study end points. Building on previous internal testing and stakeholder involvement, quantitative data collection is defined by the constructs within the ISO 9241-210-2019 Standard and the System Usability Scale (SUS), providing a benchmark usability score for DART. Guided by the participant responses to quantitative questioning, the researcher will focus the qualitative data collection on specific usability problems. These will then be graded to provide the rationale for further DART system improvements throughout the iterative cycles. RESULTS This study received approval from Queen Mary University of London Ethics of Research Committee (QMREC2018/48/048) in June 2020. At manuscript submission, the first round of individual interviews has been completed, with data collection to be completed and results published in 2021. CONCLUSIONS This study will provide evidence concerning mHealth DART system usability and acceptance determining system improvements required to support user adoption and minimize sub-optimal system usability as a potential confounder within subsequent non-inferiority clinical trials. This deliberately rigorous approach to mHealth innovation could be used as a guide for other developers of similar applications. Success should produce a safe, effective system with excellent usability, facilitating quicker and easier patient access to appropriate care while reducing the burden on primary and secondary care musculoskeletal services.

scholarly journals The impact of patient-reported outcome (PRO) data from clinical trials: a systematic review and critical analysis

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Samantha Cruz Rivera ◽  
Derek G. Kyte ◽  
Olalekan Lee Aiyegbusi ◽  
Anita L. Slade ◽  
Christel McMullan ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Case Studies ◽  
Real World ◽  
Clinical Trial Data ◽  
Research Impact ◽  
Trial Data ◽  
Patient Reported ◽  
The Impact

Abstract Background Patient-reported outcomes (PROs) are commonly collected in clinical trials and should provide impactful evidence on the effect of interventions on patient symptoms and quality of life. However, it is unclear how PRO impact is currently realised in practice. In addition, the different types of impact associated with PRO trial results, their barriers and facilitators, and appropriate impact metrics are not well defined. Therefore, our objectives were: i) to determine the range of potential impacts from PRO clinical trial data, ii) identify potential PRO impact metrics and iii) identify barriers/facilitators to maximising PRO impact; and iv) to examine real-world evidence of PRO trial data impact based on Research Excellence Framework (REF) impact case studies. Methods Two independent investigators searched MEDLINE, EMBASE, CINAHL+, HMIC databases from inception until December 2018. Articles were eligible if they discussed research impact in the context of PRO clinical trial data. In addition, the REF 2014 database was systematically searched. REF impact case studies were included if they incorporated PRO data in a clinical trial. Results Thirty-nine publications of eleven thousand four hundred eighty screened met the inclusion criteria. Nine types of PRO trial impact were identified; the most frequent of which centred around PRO data informing clinical decision-making. The included publications identified several barriers and facilitators around PRO trial design, conduct, analysis and report that can hinder or promote the impact of PRO trial data. Sixty-nine out of two hundred nine screened REF 2014 case studies were included. 12 (17%) REF case studies led to demonstrable impact including changes to international guidelines; national guidelines; influencing cost-effectiveness analysis; and influencing drug approvals. Conclusions PRO trial data may potentially lead to a range of benefits for patients and society, which can be measured through appropriate impact metrics. However, in practice there is relatively limited evidence demonstrating directly attributable and indirect real world PRO-related research impact. In part, this is due to the wider challenges of measuring the impact of research and PRO-specific issues around design, conduct, analysis and reporting. Adherence to guidelines and multi-stakeholder collaboration is essential to maximise the use of PRO trial data, facilitate impact and minimise research waste. Trial registration Systematic Review registration PROSPERO CRD42017067799.

scholarly journals Methodological Characteristics of Clinical Trials: Impact of Mandatory Trial Registration

2019 ◽  
Vol 22 ◽  
pp. 131-141
Author(s):  
Ashish Kumar Kakkar ◽  
Biswa Mohan Padhy ◽  
Sudhir Chandra Sarangi ◽  
Yogendra Kumar Gupta
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Statistical Methods ◽  
Quality Characteristics ◽  
Allocation Concealment ◽  
Trial Registration ◽  
Control Group ◽  
Study Protocols ◽  
The Impact

Purpose: Numerous studies across multiple specialties have evaluated the impact of trial registration on quality of study reports and found significant improvements over several domains. However, the impact of mandatory trial registration on the quality of clinical trial protocols remains hitherto unexplored. Methods: We carried out a retrospective cohort study of clinical trial applications submitted to drug regulatory authority of India for initial review with the objective of comparing methodological characteristics of their protocols. Since trial registration was made mandatory in the country in June 2009, we selected two study periods as between January 2007 to May 2009 (Period I) and July 2009 to December 2011 (Period II). Seventy-five protocols were randomly selected using a computer-generated list for each study period, making a total of 150 protocols. Data on twelve key methodological characteristics were collected including clearly defined primary outcomes, randomization, blinding, use of control group, statistical methods, handling of withdrawals amongst others. Results: More than 3/4th of the trial applications in the two study periods were for new chemical entities and nearly 90% were pharmaceutical industry sponsored studies. Comparing the period before and after implementation of mandatory trial registration, description of clearly defined trial outcomes improved from nearly 42% to 80% (p<0.001), sample size justifications increased from 38% to 70% (p<0.001) and use of allocation concealment improved from 24% to 49% (p=0.001). Marked improvement was also noted for blinding, description of statistical methods and handling of withdrawals and dropouts. Remaining characteristics did not change significantly between the two study periods. The mean cumulative scores for the study protocols improved significantly from 7± 0.296 in the first period to 8.93± 0.346 (p<0.001) in the second period. Conclusions: Our study found a significant improvement in the methodological quality characteristics of the protocols particularly in elements related to minimization of bias and statistical methods, which could be attributed to mandatory trial registration. Overall, the significant improvement was limited to global clinical trials, and room for improvement was noted for two quality characteristics – proportion of randomized studies and trials adequately describing the generation of allocation sequence.

The impact of newly approved drugs on clinical and operational strategies for multiple myeloma clinical trials.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19511-e19511
Author(s):  
Bhavani Krishnan ◽  
Bernadette Collins ◽  
Michael Jeffrey Cho ◽  
Tanya Partridge ◽  
Durga Vighnay ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Multiple Myeloma ◽  
Clinical Trials ◽  
Real World ◽  
Operational Strategies ◽  
Clinical Trial Enrollment ◽  
Near Term ◽  
Approved Drugs ◽  
The Impact ◽  
The U.S

e19511 Background: The global burden of multiple myeloma (MM) has increased steadily in last 3 decades. The IARC reports there were ~160,000 new cases worldwide in 2018. There has been an increase in the development and approval of more effective targeted therapy options (new immunomodulatory agents, proteasome inhibitors, and monoclonal antibodies); this, coupled with high adoption of these therapies presents a major challenge in enrollment of current ongoing clinical trials. We assessed the impact of near-term regulatory approvals on clinical trial enrollment. Methods: Public domain clinical trial enrollment data from MM studies (Phase I, I/II, II) closed/completed between 2011-2018 were used to determine enrollment trends pre and post 2014. We leveraged real-world medical claims data to project/model adoption of recently approved drugs in the U.S.; additionally, drug sales volume data was used to evaluate ex-US national adoption trends. The utilization rates of 5 recently approved drugs by regimen and line of treatment was determined. Results: In the U.S., there is a 13% increase in median enrollment duration with a corresponding 25% decrease in median p/s/m enrollment in MM studies, irrespective of phase, where enrollment was completed between 2015 -2018 compared to 2011-2014. We hypothesize that one of the factors for this increase in enrollment timeline is the approval and adoption of newly approved therapies post 2014. Two of the five recently approved drugs show a steady increase in the number of patients treated over 2016, 2017 and 2018, while one of the drugs plateaus over the same period. Outside of the U.S., our analysis confirms the existence of gaps in time to approval /adoption of recently approved drugs; for example, we observe a two-year delay in approval/adoption for one of the drugs in France compared to the other countries in Western Europe. Conclusions: There are over 10 investigational MM drugs currently in development which are anticipated to be granted approval between 2019-2021. Factoring the real-world adoption of near-term drug approval into global clinical and operational strategies offers insights into mitigating potential future enrollment challenges.

Adoption of immuno-oncology in NSCLC, a real-world study in EU5.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20631-e20631
Author(s):  
Alejandra Martinez De Pinillos ◽  
Isabel Ricote Lobera ◽  
Cristina Martinez ◽  
Caroline Anger ◽  
Filippo Guglielmetti ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Performance Status ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Patient Profile ◽  
Period 2 ◽  
Level Data ◽  
The Impact ◽  
New Evidence

e20631 Background: To date, there are no robust studies in real world practice describing the use of IO (immuno-oncology) treatments in advanced/metastatic (adv/m) NSCLC. The available evidence in Europe is limited to observational studies of small size. This study aims to understand the impact of IO in adv/mNSCLC and study the profile of patients currently receiving these treatments. Methods: 20,157 cases of 1st and 2nd line adv/mNSCLC patients between October 2016 and September 2018 in EU5 (France, Germany, Spain, Italy, UK) were identified within Oncology Dynamics, an IQVIA oncology syndicated cross sectional survey collecting anonymized patient-level data. Patient profile was described, and two groups were created to assess differences in the use of IO treatments (nivolumab, pembrolizumab, atezolizumab, ipilimumab, durvalumab) across 2 time periods: #1 October 2016 - September 2017 (n = 9,310); #2 October 2017 - September 2018 (n = 10,847). Results: IO treatments increased 15% in 1st line adv/mNSCLC (13% in non-squamous and 23% in squamous histology) and 11% in 2nd line across periods; reaching treatment shares of 20.3% and 67.9% in 1st line and 2nd line in Period 2. Within IO-treated patients, 9.5% in 1st line and 13.6% in 2nd line had ECOG ≥2, and 27% were > 71 years old. The use of IO in 1st line patients without mutations (EGFR/ALK/ROS1/BRAF) increased by 24%, while standard chemotherapy decreased by 21%. Conclusions: IO treatments had a rapid adoption in Europe last year, influenced by its approval in 1st line adv/mNSCLC and by clinical guidelines recommendations. Ongoing clinical trials may suggest a growing trend in the future that could potentially impact in healthcare systems. In addition, real world patients treated with IO are older and have a worse performance status than those widely included in clinical trials. An evaluation of these results sheds light into IO treatments in NSCLC and may contribute to the design of real-world studies to generate new evidence and optimize the use of these class of drugs in clinical practice.[Table: see text]

scholarly journals Assessing the impact on pharmacists’ time by introducing a technician screening process for clinical trial prescriptions

2021 ◽  
Vol 29 (Supplement_1) ◽  
pp. i46-i47
Author(s):  
D Mistry ◽  
S Awan ◽  
E Lundy ◽  
C Bedford ◽  
H Thorp ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Data Collection ◽  
Hospital Pharmacy ◽  
Good Practice ◽  
Advisory Group ◽  
Service Improvement ◽  
Data Collection Tool ◽  
Patient Counselling ◽  
The Impact

Abstract Introduction Various national guidance from the Lord Carter 2016 report to the NHS Long term plan have emphasised the need to transform traditional hospital pharmacy and make work streams more efficient.[1] A clinical trials pharmacist has historically validated clinical trial medicines. Whilst this is good practice for non-chemotherapy prescriptions, it is not a requirement of the Clinical Trial Regulations.[2] Interruption to validate trial prescriptions can have a negative impact on pharmacists’ duty and consequently patient outcomes. With limited data available, this issue has been highlighted by anecdotal evidence. Due to the often complex requirements associated with trials, the research team are responsible for assessing the suitability of treatment. This includes checking interactions with concomitant medication, reviewing blood results and patient counselling. The clinical aspect of the pharmacist validation is therefore removed, allowing technicians to be involved in the screening of suitable prescriptions. Much is written on technicians extending their roles in the clinical setting, but this service improvement focuses on enhancing their role within the pharmacy clinical trials department. Aim To evaluate the amount of pharmacists’ time saved by the introduction of technician screening of clinical trial prescriptions. Method A risk-based proforma was created and used by a pharmacist to assess clinical trial prescriptions for the suitability of screening by a Band 7 technician. Only prescriptions with pre-printed doses, no aseptic preparation or additional medicines, were approved for technician screening. The process of screening therefore only involves the checking of patient and prescriber details, allergy status and possibly a medication randomisation. The technicians under-went an in-house training including the screening of prescriptions under pharmacist supervision. A quantitative data collection tool was used to review the screening / validation of all nonchemotherapy clinical trial prescriptions received at two sites over a two-week period in September 2020. The data collection tool was piloted and all data was analysed using Microsoft Excel. Results A total of 89 prescriptions were received. 56 (63%) were eligible for technician screening, of which a suitable technician validated 50%. Across both sites a total time of 360 minutes were spent validating/screening prescriptions including solving prescription related issues. Combining the time taken by a pharmacist to return from a clinical area and screening time consequently saved a total of 227 minutes of pharmacists’ time. Conclusion Distributing the workload amongst trained staff saves pharmacist’s time, which can be utilised on clinical and complex tasks. This does not eliminate the requirement of a pharmacist to validate prescriptions however; it reduces the frequency and streamlines the service. Further data collection is required to analyse the direct impact on patients’ and any changes in the number of reported errors. A limitation to the study is the lack of data prior to implementation as a comparator. Additionally, during data collection there were no suitable technicians available at one site due to the Covid-19 pandemic, resulting in only 50% of eligible prescriptions being screened by a technician. Ultimately, this does not change the outcome; enhancing technician’s roles allows pharmacists’ time to be used more efficiently. References 1. Royal Pharmaceutical Society. Shaping Pharmacy for the future. Hospital Pharmacy: A briefing for members in England. 2017. Available at: https://www.rpharms.com/Portals/0/Hospital%20pharmacy%20briefing%20-%20final.pdf [Accessed: 11/10/20] 2. National Pharmacy Clinical Trials Advisory Group. Professional Guidance on Pharmacy Services for Clinical Trials v2.1. 2019. Available at: https://www.rpharms.com/Portals/0/RPS%20document%20library/Open%20access/Hospital%20Pharmacy%20Hub/Practice_Guidance_on_Pharmacy_Services_for_Clinical_Trials_v2.1.pdf?ver=2020-09-18-095937-733 [Accessed: 09/10/20]

scholarly journals Clinical, Cytogenetic Characteristics and Survival of Acute Leukemia in a National Research Center Database, 10-Year Real-World Data Review

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3062-3062
Author(s):  
Yan Li ◽  
Junping Zhang ◽  
Hui Wei ◽  
Ying Wang ◽  
Bingcheng Liu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Acute Leukemia ◽  
Real World ◽  
Research Center ◽  
Real World Data ◽  
World Data ◽  
Chromosomal Karyotype ◽  
The Impact

Abstract Introduction Major resources of our current knowledge on acute leukemia epidemiology and prognosis are based on data from clinical trials. Due to the selective bias of clinical trials, data might differ from the general leukemia population in real-life setting. National Clinical Research Center for Blood Disease established a comprehensive database through the electronic health records (EHR) to facilitate research of the hematologic cancers i.e. acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and acute promyelocytic leukemia (APL). The aim of the database is to gain insight into the epidemiology of these cancers, to evaluate treatment responses, to compare results between geographical regions of China. Furthermore, with the privilege of national research center, the database expects to identify prognostic and predictive factors for outcome to improve the quality of treatment and patients care. Methods The database development was initiated in 2001. Standard data elements were established to capture the key clinical variables. For individual patients, data from EHRs were extracted, integrated and quality checked. The implement of database facilitated the clinical professions to identify eligible patients, establish research projects, conduct retrospective analysis and follow-up patient outcomes. Continued efforts were made for improving the construction and quality of the database over two decades. We performed a 10-year real-world data review in the database to evaluate the quality of the recorded data and, moreover to describe the clinical, cytogenetic characteristics and survival of acute leukemia patients. The completeness for collected variables was acceptable for statistical analysis. In total, 3,404 patients (1,895 males and 1,509 females) who were diagnosed and treated between Jan. 1, 2010 and Dec. 31, 2020 were enrolled. A substantial proportion (&gt;60%) of patients were residents of the northern and northeast region of China. Demographic and baseline characteristics also included age, age class, baseline blood test, transplantation and research participation. Molecular mutations such as nucleophosmin-1 (NPM1), FMS-related tyrosine kinase 3 (FLT3), and CCAAT/enhancer-binding protein alpha (CEBPA) et al were included in the screening panels. We explored the treatment remission rate and prognosis of different chromosomal karyotype groups among AML patients. Results The patient numbers of the AML, ALL and APL subgroups were 2,345, 769 and 290 respectively. Blood routine results well demonstrated the clinical characteristics of each subgroup (Tbl. 1). In AML group, the frequencies of NPM1, FLT3-ITD, KIT and CEBPA double mutations were 17.9%, 13.2%, 8.7% and 10.1%, respectively (Tbl. 2). In term of ALL, 640 cases (83.2%) were B-ALL and 129 (16.8%) were T-ALL. Among B-ALL, 256 cases (33.3%) were Ph positive. 10-year analysis for overall survival shown that AML patients had better outcomes as compared with ALL group (Fig. 1). In this database, 1,780 AML cases (excluding APL) were enrolled in cytogenetic analysis. The survival rates of different cytogenetic risk groups from our real-world data were separated by the ELN2017 and MRC risk stratification respectively (Fig. 2A-B). Remarkably, we found two rare but recurrent abnormalities, 16 cases with t(7;11) (p15;p15) and 12 cases with t(16;21)(p11;q22/q24;q22). Cases showed high relapse and mortality rate. Compared with the normal karyotype group, the survival of both subentities was worse and transplantation might be recommended in CR1 phase (Fig. 2C), therefore, we recommend that these two subtypes might be regarded as the worse risk group, although neither is mentioned in the current guidelines. The incidence of t(8;21) in our database was 17.9% (Fig. 3). To explore the impact of additional chromosomal abnormalities on the prognosis of t(8;21), we found that the overall survival of patients with additional trisomy 4 was worse than those without trisomy 4 (Fig. 2D), which was rarely mentioned in previous reports. Conclusion The real-world database is of great importance for defining the comprehensive features of AML, APL and ALL in clinical setting. The results offered a remarkable contribution to our knowledge on acute leukemia and identified the prognosis of rare chromosomal karyotype in AML. Figure 1 Figure 1. Disclosures Wang: AbbVie: Consultancy; Astellas Pharma, Inc.: Research Funding.

Final Results of a Large, Community Based Study Evaluating the Impact of First and Subsequent Cycle Pegfilgrastim on Neutropenic Events in NHL and HD Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1153-1153 ◽  
Author(s):  
Stephen J. Noga ◽  
Janak Choksi ◽  
Beiying Ding ◽  
Lyndah Dreiling ◽  
Howard Ozer
Keyword(s):  
Clinical Trials ◽  
Dose Intensity ◽  
Community Practice ◽  
Primary Analysis ◽  
Real World Data ◽  
Community Based ◽  
Serious Adverse Events ◽  
Ct Dose ◽  
The Impact ◽  
Dose Reductions

Abstract Introduction: Most alterations to chemotherapy (CT) dose and schedule are due to neutropenic events, which mainly occur in the 1st cycle. A nationwide survey found that of 4522 patients (pts) with diffuse, aggressive non-Hodgkin’s lymphoma (NHL) treated with CHOP-like regimens in community practice, 40% experienced CT dose reductions, and 24% experienced CT dose delays (Lyman 2004). The ability of pegfilgrastim to reduce complications of CT-induced neutropenia has been established in clinical trials for pts receiving moderately (Vogel 2005) and highly (Holmes 2002) myelosuppressive CT. This prospective, community-based study evaluated the efficacy of 1st cycle pegfilgrastim in pts with NHL receiving CT in community practice. Methods: Pts ≥ 18 yrs with cancers other than leukemia or MDS were eligible, including those with major comorbidities who are generally not eligible for clinical trials. Key exclusions were weekly CT and concurrent radiotherapy. Pts received pegfilgrastim 6mg ~24 hours after CT in each cycle (up to 8 cycles). Endpoints included neutropenic complications and CT dose reductions and delays. Additionally, average relative dose intensity (ARDI) was calculated for major standard regimens. Point estimates and 95% confidence limits (CL) are provided. Results: This open-label, single-arm study enrolled 2249 pts at 319 sites. Of these, 325 pts with NHL and 46 pts with Hodgkin’s disease (HD) were included in the primary analysis set. The mean (SD) age was 65 (13) years for NHL pts and 41 (14) for HD pts. 69% of NHL pts and 26% HD pts had advanced (III–IV) disease, 90% of NHL pts and 98% of HD pts had ECOG status 0 or 1, and 31% of NHL pts and 26% of HD pts had major comorbidities (eg. vascular disease, diabetes). 49% of NHL pts received standard CHOP ± R (cyclophosphamide, doxorubicin, vincristine, and prednisone ± rituximab) and 78% of HD pts received standard ABVD (bleomycin, dacarbazine, doxorubicin, vinblastine). Few pts experienced neutropenic complications (table). All serious adverse events were consistent with those observed in pts receiving myelosuppressive CT. Conclusions: These results represent ‘real-world’ data as the only major entry criterion for pts was a confirmed diagnosis of malignancy. Pts in our study received myelosuppressive CT with very few neutropenia-related alterations in CT dose and schedule supporting the use of pegfilgrastim from the 1st cycle of CT. Use of pegfilgrastim allowed maintenance of RDI with minimal CT dose delays and reductions. Incidence % (95% CL) NHL HD 1 physician reported; 2standard reference dose and planned cycle length were used to calculate DI in the denominator of RDI Hospitalization related to neutropenia in cycle 1 9 (6, 13) 4 (0.5, 15) Hospitalization related to FN in cycle 1 6 (4, 9) 0 (0, 8) FN in cycle 1 (ANC&lt;0.5×109/L and temperature 38.2°C) 8 (5, 12) 0 (0, 8) Incidence of grade 3/4 neutropenia in cycle 1 37 (32, 42) 4 (0.5, 15) Neutropenia-related IV antibiotic use in cycle 1 9 (6, 12) 4 (0.5, 15) Neutropenia-related CT dose reductions in cycle 21 2 (1, 5) 0 (0, 8) Neutropenia-related CT dose delays in cycle 21 2 (1, 5) 0 (0, 8) ARDI (mean % [SD])2 CHOP ± R every 21 days 77 (23) ABVD every 14 days 83 (26)

Biliary tract cancer (BTC) in the elderly: A real-world tertiary cancer center experience.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 492-492 ◽  
Author(s):  
Massimiliano Salati ◽  
Francesco Caputo ◽  
Krisida Cerma ◽  
Andrea Spallanzani ◽  
Fabio Gelsomino ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Advanced Disease ◽  
Locally Advanced ◽  
The Elderly ◽  
Categorical Variables ◽  
Rank Test ◽  
Survival Difference ◽  
The Impact ◽  
To Receive

492 Background: Although BTC is mostly a disease of the elderly, only limited data ara available on the optimal management of this patient (pt) population. In fact, older pts are underepresented in clinical trials and results are seldom reported by age group. In this study, we aimed at evaluating pattern of care and treatment outcome in BTC aged ≥ 70 years and comparing them with their younger counterparts. Methods: Medical records of BTC followed at the Modena Cancer Centre from 2007 and 2019 were retrospectively reviewed.. Overall survival (OS) was estimated with the Kaplan-Meier curves and compared by log-rank test. Differences between categorical variables were assessed using the chi square test. Univariate and multivariate analyses were performed to assess the impact of covariates on survival. Results: A total of 120 BTC patients (49%) ≥ 70 were included in the analysis. 54% (64) were female, 47% (56) had iCCA, 41% (49) GBC, and 12% (15) eCCA. 68% (81) had unresectable locally advanced or metastatic disease. 32% (39) underwent surgical resection, 60% (72) were treated with first-line chemotherapy (1L), while 29% (21) of them went on to receive second-line (2L). No differences in terms of both chance to receive surgery (p=0.59) and survival (p=0.25) were recorded compared to youngers. In the advanced-disease setting, median OS was 8 months and was significantly worse than that of the younger counterparts (p<0.001). Older patients were less likely to receive 1L (p<0.001) and 2L (p<0.001) chemotherapy and doublet regimens (p<0.001). Female gender (p=0.031), ECOG PS 0 (p<0.001), stage III (p<0.001) and NLR>3 (p<0.001) were independently associated with a better prognosis in older BTC receiving 1L, with 1-year OS of 82% (95%CI 68-91, p=0.031). Conclusions: In this real-world study, no survival difference was found between older and non-older surgically-treated patients. Contrariwise, elderly BTC were less frequently treated with chemotherapy for advanced disease and their outcome is poorer than youngers. However, clinical and biochemical prognostic have been identified that may assist in selecting older pts more likely to benefit from systemic treatment, both in clinical trials and daily practice.

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