scholarly journals The opportunity of patient-journey studies for academic clinical research in oncology

BMJ Open ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. e052871
Author(s):  
Francesco Perrone ◽  
Raimondo Di Liello ◽  
Piera Gargiulo ◽  
Laura Arenare ◽  
Lorenzo Guizzaro ◽  
...  

A wave of new treatments and treatment combinations are becoming available for solid tumours. Trials performed to obtain registration establish a positive benefit-risk but unavoidably leave many questions unanswered on place-in-therapy and the relative efficacy of different treatment sequences. Such limitations create problems in terms of strength of treatment guidelines and reimbursement (in countries where a public payer exists). Data on new drugs arriving during the last 10 years for the treatment of hepatocellular carcinoma and renal cancer are reported as an example of how the fortunate condition of having new effective treatments may translate into uncertainty regarding the optimal treatment plan. We suggest that academic research should react to such limitations and propose a model of patient-journey study (PJS), where patients are followed from the initial diagnosis across subsequent lines of treatment. A PJS master protocol might include at each node of clinical decision either the possibility of choosing treatment according to guidelines (generating prospective real-world evidence) or the possibility to randomise where uncertainty exists (generating comparative effectiveness data). PJS protocols might be adaptively modified every time a new drug arrives on the market. Overall, methodologically sound analyses of PJS will produce knowledge on the efficacy and the effectiveness of different treatment pathways and might significantly optimise treatment of patients in clinical practice. PJS would represent a jump from a few snapshots (trials performed to get regulatory approval) to a full movie (evidence on the relative value of treatment pathways).

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 18-19
Author(s):  
Steven E. Labkoff ◽  
Kathy E. Giusti ◽  
Paul A. Giusti ◽  
Ryan Wilcox ◽  
Derrick Haslem ◽  
...  

Introduction Clinical decision support (CDS) technology has the potential to improve health outcomes by offering physicians an informational resource to support review and application of best pratices.1 The Multiple Myeloma Research Foundation (MMRF) and Intermountain Healthcare (IMH) conducted a study to assess the suitability of a single health system's data for a myeloma-specific CDS tool that visualizes treatment pathways, and to assess the effort needed to support a CDS program.2 This research is part of a longer-term effort to explore how CDS technology can help: - increase awareness of and apply treatment guidelines by visualizing pathways for specific MM patient cohorts - improve understanding of treatment variation within health systems - improve outcomes research by showing relationships between treatments and outcomes Methods IA12 data from the CoMMpass study3 was used to create a CDS tool prototype. These data were aggregated into state and transition maps to identify nodes and pathways with corresponding outcomes, including response, progression-free survival (PFS), and overall survival (OS). Intervening patient states were displayed using Sankey diagrams [Fig. 1]. We also tested if EMR data from a community health system (i.e., IMH) could support such visualization. The team designed a study protocol and obtained IRB approval. Inclusion criteria included patients with active MM between January 2016-June 2018; adult aged 18 years to 89 years at diagnosis of active or smoldering MM. An IMH-specific data dictionary was assessed for variable importance, quantity, and ease of acquisition. [Table 1]. IMH then manually abstracted prioritized structured (eg: labs) and non-structured (eg: notes) data for use in the tool. Results Ninety-six of an initial 146 patients meeting eligibility criteria had sufficient data usable for the study, reflecting 44 unique drug combinations across 9 lines of therapy. The tool was able to associate and visualize all patients and their clinical states and transitions to their outcomes. Clinical data was typically complete (99% of the time), including key clinician-derived data, such as ECOG scores (78%) and treatment response (99%). 569 person-hours were required to conduct the abstraction activity on 96 cases, averaging 5.9 hours/patient Discussion The IMH portion of the study supports the hypothesis that a community health system can provide sufficient high-quality information to power a CDS tool with priority features. Only 65% (96/146) of the initial study group had usable data because some patients had received partial care outside of the IMH integrated delivery network (IDN) leaving associated data inaccessible. Initial biostatistical analysis suggests that roughly 750-1000 complete patient records would be required for statistically significant outcomes research with granularly stratified cohorts. The MMRF is currently recruiting 5-7 additional large IDNs to obtain the patients to power more generalizable functionality. References 1 McKie PM, Kor DJ, Cook DA, Kessler ME, Carter RE, Wilson PM, et al. Computerized advisory decision support for cardiovascular diseases in primary care: a cluster randomized trial. Am J Med [Internet]. 2019 Dec 18 [cited 2020 Mar 5]. Available from: https://doi.org/10.1016/j.amjmed.2019.10.039 2 Garcelon N, Burgun A, Salomon R, Neuraz A. Electronic health records for the diagnosis of rare diseases. Kidney Int [Internet]. 2020 Jan 14 [cited 2020 Mar 5]. Available from: https://doi.org/10.1016/ j.kint.2019.11.037 3 Christofferson A, Nasser S, Aldrich J, Penaherrera D, Legendre C, Benard B, et al. Integrative analysis of the genomic landscape underlying multiple myeloma at diagnosis: an Mmrf Commpass analysis. Blood. 2017 Dec 7; 130 (Supplement 1): 326. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 38 (04) ◽  
pp. 432-437
Author(s):  
Adam Swersky ◽  
Laura Kulik ◽  
Aparna Kalyan ◽  
Karen Grace ◽  
Juan Carlos Caicedo ◽  
...  

AbstractHepatocellular carcinoma (HCC) is the most common primary liver cancer and a major cause of cancer-related morbidity and mortality around the world. Frequently, concurrent liver dysfunction and variations in tumor burden make it difficult to design effective and standardized treatment pathways. Contemporary treatment guidelines designed for an era of personalized medicine should consider these features in a more clinically meaningful way to improve outcomes for patients across the HCC spectrum. Given the heterogeneity of HCC, we propose a detailed clinical algorithm for selecting optimal treatment using an evidence-based and practical approach, incorporating liver function, tumor burden, the extent of disease, and ultimate treatment intent, with the goal of individualizing clinical decision making.


2021 ◽  
pp. 026988112110324
Author(s):  
David J Heal ◽  
Sharon L Smith

Background: Binge-eating disorder (BED) is a common psychiatric condition with adverse psychological and metabolic consequences. Lisdexamfetamine (LDX) is the only approved BED drug treatment. New drugs to treat BED are urgently needed. Methods: A comprehensive review of published psychopathological, pharmacological and clinical findings. Results: The evidence supports the hypothesis that BED is an impulse control disorder with similarities to ADHD, including responsiveness to catecholaminergic drugs, for example LDX and dasotraline. The target product profile (TPP) of the ideal BED drug combines treating the psychopathological drivers of the disorder with an independent weight-loss effect. Drugs with proven efficacy in BED have a common pharmacology; they potentiate central noradrenergic and dopaminergic neurotransmission. Because of the overlap between pharmacotherapy in attention deficit hyperactivity disorder (ADHD) and BED, drug-candidates from diverse pharmacological classes, which have already failed in ADHD would also be predicted to fail if tested in BED. The failure in BED trials of drugs with diverse pharmacological mechanisms indicates many possible avenues for drug discovery can probably be discounted. Conclusions: (1) The efficacy of drugs for BED is dependent on reducing its core psychopathologies of impulsivity, compulsivity and perseveration and by increasing cognitive control of eating. (2) The analysis revealed a large number of pharmacological mechanisms are unlikely to be productive in the search for effective new BED drugs. (3) The most promising areas for new treatments for BED are drugs, which augment noradrenergic and dopaminergic neurotransmission and/or those which are effective in ADHD.


2021 ◽  
Vol 10 (8) ◽  
pp. 1763
Author(s):  
Marta Mazzetti ◽  
Giulia Marconi ◽  
Martina Mancinelli ◽  
Antonio Benedetti ◽  
Marco Marzioni ◽  
...  

Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are two chronic cholestatic liver diseases affecting bile ducts that may progress to biliary cirrhosis. In the past few years, the increasing knowledge in the pathogenesis of both diseases led to a growing number of clinical trials and possible new targets for therapy. In this review, we provide an update on the treatments in clinical use and summarize the new drugs in trials for PBC and PSC patients. Farnesoid X Receptor (FXR) agonists and Pan-Peroxisome Proliferator-Activated Receptor (PPAR) agonists are the most promising agents and have shown promising results in both PBC and PSC. Fibroblast Growth Factor 19 (FGF19) analogues also showed good results, especially in PBC, while, although PBC and PSC are autoimmune diseases, immunosuppressive drugs had disappointing effects. Since the gut microbiome could have a potential role in the pathogenesis of PSC, recent research focused on molecules that could change the microbiome, with good results. The near future of the medical management of these diseases may include new treatments or a combination of multiple drugs targeting different signaling pathways at different stages of the diseases.


Coronaviruses ◽  
2021 ◽  
Vol 02 ◽  
Author(s):  
Martin Amé ◽  
Esraa Samy Abu Serea ◽  
Ahmed Esmail Shalan ◽  
A. Guillermo Bracamonte

: The design of new Drugs, Molecules, Nano-, and Microstructures for targeted applications along the pass of the time within the history of Chemistry and Clinical Analysis showed to be of high impact on Life Sciences. In this context, and mainly for the actual Corona Virus Pandemic status, it should be highlighted the importance of a fast response. Thus, the developments of differents approaches looking for improved and higher sensitive solutions in the Biodetection field accompanied with new treatments of SARS CoV-2 are required. In this way, in this short communication based on the latest Research publications it was afforded and discussed the following topics: i) the importance of non-covalent interactions from antibody-antigen recognition events, ii) the genomic factor, and iii) the use of non-covalent interactions in different Optical detection systems and Lab-On particles. Moreover, it was afforded the theme related with the importance of new treatments in progress, such development of new vaccines; and current state of the pandemic situation. So, it was discussed and stimulated the improvement of innovative Multifunctional Nanophotonic approaches intended for SARS CoV-2 detection accompanied with potential targeted treatments.


2020 ◽  
Vol 14 ◽  
pp. 117954682095341 ◽  
Author(s):  
Todd C Villines ◽  
Mark J Cziraky ◽  
Alpesh N Amin

Real-world evidence (RWE) provides a potential rich source of additional information to the body of data available from randomized clinical trials (RCTs), but there is a need to understand the strengths and limitations of RWE before it can be applied to clinical practice. To gain insight into current thinking in clinical decision making and utility of different data sources, a representative sampling of US cardiologists selected from the current, active Fellows of the American College of Cardiology (ACC) were surveyed to evaluate their perceptions of findings from RCTs and RWE studies and their application in clinical practice. The survey was conducted online via the ACC web portal between 12 July and 11 August 2017. Of the 548 active ACC Fellows invited as panel members, 173 completed the survey (32% response), most of whom were board certified in general cardiology (n = 119, 69%) or interventional cardiology (n = 40, 23%). The survey results indicated a wide range of familiarity with and utilization of RWE amongst cardiologists. Most cardiologists were familiar with RWE and considered RWE in clinical practice at least some of the time. However, a significant minority of survey respondents had rarely or never applied RWE learnings in their clinical practice, and many did not feel confident in the results of RWE other than registry data. These survey findings suggest that additional education on how to assess and interpret RWE could help physicians to integrate data and learnings from RCTs and RWE to best guide clinical decision making.


2020 ◽  
Author(s):  
Jin-Hyeok Park ◽  
Jeong-Heum Baek ◽  
Sun Jin Sym ◽  
KangYoon Lee ◽  
Youngho Lee

Abstract Background: Clinical Decision Support Systems (CDSSs) have recently attracted attention as a method for minimizing medical errors. Existing CDSSs are limited in that they do not reflect actual data. To overcome this limitation, we propose a CDSS based on deep learning. Methods: We propose the Colorectal Cancer Chemotherapy Recommender (C3R), which is a deep learning-based chemotherapy recommendation model. Our model improves on existing CDSSs in which data-based decision making is not well supported. C3R is configured to study the clinical data collected at the Gachon Gil Medical Center and to recommend appropriate chemotherapy based on the data. To validate the model, we compared the treatment concordance rate with the National Comprehensive Cancer Network (NCCN) Guidelines, a representative set of cancer treatment guidelines, and with the results of the Gachon Gil Medical Center’s Colorectal Cancer Treatment Protocol (GCCTP). Results: For the CR3 model, the treatment concordance rates with the NCCN guidelines were 70.5% for Top-1 Accuracy and 84% for Top-2 Accuracy. The treatment concordance rates with the GCCTP were 57.9% for Top-1 Accuracy and 77.8% for Top-2 Accuracy. Conclusions: This model is significant, i.e., it is the first colon cancer treatment clinical decision support system in Korea that reflects actual data. In the future, if sufficient data can be secured through cooperation among multiple organizations, more reliable results can be obtained.


2021 ◽  
Vol 7 (1) ◽  
pp. 36
Author(s):  
Soedarsono Soedarsono

Tuberculosis (TB) still becomes a public health crisis. Drug-resistant TB (DR-TB) becomes a concern as the increasing DR-TB cases in countries with high TB burden. The 2017 World Health Organization (WHO) guideline recommended a combination of TB treatment consisting of 2 months of intensive phase with isoniazid (H), rifampisin (R), pyrazinamid (Z), and ethambutol (E), followed by 4 months of continuation phase with HR daily. WHO has updated DR-TB treatment guidelines several times. In 2016, WHO recommended shorter regimen and individual regimen based on certain conditions. The most updated 2020 WHO guideline recommended the short regimen consisting of all oral drugs as well as changes in the grouping of medicines used in DR-TB regimens in longer/individual regimens. Bedaquiline, delamanid, pretomanid, and sutezolid are new drugs which have been studied for their uses as anti-TB drugs (ATD). Bedaquilin and delamanid, which have passed phase 3 trials, have been approved and recommended by WHO for DR-TB treatment. Repurposed drugs have been used for DR-TB treatment during the time of evaluation of drugs list and regimens for DR-TB treatment. Fluoroquinolones, clofazimine, linezolid, carbapenem, amoxicillin/clavulanic acid are repurposed drugs. TB and DR-TB management will be updated at any time, based on the latest findings in studies, to evaluate and improve the effectiveness of current treatments. Prevention of active TB disease by the treatment of latent TB infection (LTBI) is also a critical component of the end TB strategy by WHO. Therefore, the development of new drugs for the LTBI treatment is also needed.


2021 ◽  
pp. 106002802110592
Author(s):  
Barbara Blaylock ◽  
Xiaoli Niu ◽  
H. Edward Davidson ◽  
Stefan Gravenstein ◽  
Ronald DePue ◽  
...  

Background Assessing chronic obstructive pulmonary disease (COPD) severity is challenging in nursing home (NH) residents due to incomplete symptom assessments and exacerbation history. Objective The objective of this study was to predict COPD severity in NH residents using the Minimum Data Set (MDS), a clinical assessment of functional capabilities and health needs. Methods A cohort analysis of prospectively collected longitudinal data was conducted. Residents from geographically varied Medicare-certified NHs with age ≥60 years, COPD diagnosis, and ≥6 months NH residence at enrollment were included. Residents with severe cognitive impairment were excluded. Demographic characteristics, medical history, and MDS variables were extracted from medical records. The care provider–completed COPD Assessment Test (CAT) and COPD exacerbation history were used to categorize residents by Global Initiative for Chronic Lung Disease (GOLD) A to D groups. Multivariate multinomial logit models mapped the MDS to GOLD A to D groups with stepwise selection of variables. Results Nursing home residents (N = 175) were 64% women and had a mean age of 77.9 years. Among residents, GOLD B was most common (A = 13.1%; B = 44.0%; C = 5.7%; D = 37.1%). Any long-acting bronchodilator (LABD) use and any dyspnea were significant predictors of GOLD A to D groups. The predicted MDS-GOLD group (A = 6.9%; B = 52.6%; C = 4.6%; D = 36.0%) showed good model fit (correctly predicted = 60.6%). Nursing home residents may underuse group-recommended LABD treatment (no LABD: B = 53.2%; C = 80.0%; D = 40.0%). Conclusion and Relevance The MDS, completed routinely for US NH residents, could potentially be used to estimate COPD severity. Predicted COPD severity with additional validation could provide a map to evidence-based treatment guidelines and may help to individualize treatment pathways for NH residents.


2021 ◽  
pp. 1-8
Author(s):  
Tilman Steinmetz ◽  
Angela Ernst ◽  
Martin Hellmich ◽  
Melanie Heinz ◽  
Uwe Totzke

<b><i>Introduction:</i></b> New drugs for multiple myeloma have considerably increased the options for consecutive treatment lines in regular care. Official treatment guidelines still discuss several regimens per line, and therefore, current practice is of topical interest. Large cross-sectional studies revealed a greater than linear loss of patients reaching consecutive treatment lines of ever decreasing effectiveness. <b><i>Methods:</i></b> In a longitudinal approach, we analyzed data of all 145 multiple myeloma patients treated in our outpatient clinic in Germany between January 1, 2012, and December 31, 2019, using a time-to-event analysis with death as competitive risk. <b><i>Results:</i></b> The estimated incidences of reaching the 2nd, 3rd, 4th, and 5th lines of therapy were 88, 66, 44, and 30%, respectively. Median times to subsequent treatment lines were 34, 18, 14, 13, and 15 months, respectively. <b><i>Discussion:</i></b> Percentages of patients reaching later therapy lines were considerably greater than predicted by cross-sectional studies and median times after the 1st line did not suggest a further decrease in effectiveness, while use of new drug regimens was similar to that reported in cross-sectional studies. <b><i>Conclusion:</i></b> Effectiveness of later therapy lines appears to be underestimated by cross-sectional analyses, and the conveyed focus on 1st-line treatment for multiple myeloma needs to be scrutinized.


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