scholarly journals External validity of somatostatin analogues trials in advanced neuroendocrine neoplasms: the GETNE-TRASGU study

2021 ◽  
Author(s):  
Paula Jimenez-Fonseca ◽  
Alberto Carmona-Bayonas ◽  
Angela Lamarca ◽  
Jorge Barriuso ◽  
Angel Castaño ◽  
...  
Keyword(s):  
Real World ◽  
External Validity ◽  
Randomized Clinical Trials ◽  
Cox Model ◽  
Analytical Data ◽  
Somatostatin Analogues ◽  
Unknown Primary ◽  
Octreotide Lar ◽  
Well Differentiated ◽  
Lanreotide Autogel

Introduction: Somatostatin analogues (SSA) prolong progression-free survival (PFS) in patients with well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). However, the eligibility criteria in randomized clinical trials (RCTs) have been restricted, which contrasts with the vast heterogeneity found in NETs. Methods: We identified patients with well-differentiated (Ki67% ≤20%), metastatic GEP-NETs treated in first-line with SSA monotherapy from the Spanish R-GETNE registry. The therapeutic effect was evaluated using a Bayesian Cox model. The objective was to compare survival-based outcomes from real world clinical practice versus RCTs. Results: The dataset contained 535 patients with a median age of 62 years (range: 26-89). The median Ki67% was 4 (range: 0-20). The most common primary tumor sites were: midgut, 46%; pancreas, 34%; unknown primary, 10%; and colorectal, 10%. Half of the patients received octreotide LAR (n=266) and half, lanreotide autogel (n=269). The median PFS was 28.0 months (95% CI, 22.1-32.0) for octreotide vs 30.1 months (95% CI, 23.1-38.0) for lanreotide. The overall hazard ratio for lanreotide vs octreotide was 0.90 (95% credible interval, 0.71-1.12). The probability of effect sizes >30% with lanreotide vs octreotide was 2% and 6% for midgut and foregut NENs, respectively. Conclusion: Our study evaluated the external validity of RCTs examining SSAs in the real world, as well as the main effect-modifying factors (progression status, symptoms, tumor site, specific metastases, and analytical data).. Our results indicate that both octreotide LAR and lanreotide autogel had a similar effect on PFS. Consequently, both represent valid alternatives in patients with well-differentiated, metastatic GEP-NENs.

Lanreotide Autogel Therapy in Patients with Acromegaly –Current Role and Perspectives for the Future

2010 ◽  
Vol 6 (2) ◽  
pp. 36
Author(s):  
Josef Marek ◽  
Keyword(s):  
Healthcare Professionals ◽  
Single Injection ◽  
Somatostatin Analogues ◽  
Hormonal Control ◽  
Somatostatin Analogue ◽  
Octreotide Lar ◽  
Care Givers ◽  
Active Release ◽  
Long Acting ◽  
Lanreotide Autogel

Lanreotide Autogel is a long-acting (effective for four to six weeks after a single injection) somatostatin analogue that normalises growth hormone (GH) and insulin-like growth factor I levels in about 50% of patients. It causes tumour volumes to shrink by more than 20% in 72–85% of patients. These effects are similar to those with octreotide long active release (LAR). Similarly, there are no differences between octreotide LAR and lanreotide Autogel in improvement of cardiac function, glycometabolic effects or occurrence of side effects, including cholelithiasis. In comparison to octreotide LAR, lanreotide Autogel has the advantage of being available in a convenient pre-filled syringe and it can be injected subcutaneously by patients or their care-givers/partners, omitting the necessity of injections by healthcare professionals. The efficacy of lanreotide can be increased by combination with dopamine agonists. Co-administration of lanreotide Autogel with pegvisomant appears to be safe and to improve hormonal control in a majority of patients with acromegaly partially controlled by somatostatin analogues alone.

A Preregistered Validation Study of the Taylor Aggression Paradigm

2017 ◽  
Author(s):  
David Skylan Chester
Keyword(s):  
Aggressive Behavior ◽  
Validation Study ◽  
Real World ◽  
External Validity ◽  
State Level ◽  
Taylor Aggression Paradigm ◽  
Psychological Science ◽  
Laboratory Measure ◽  
Behavioral Tasks ◽  
Preliminary Support

The Taylor Aggression Paradigm (TAP) is a frequently-used laboratory measure of aggressive behavior. However, the flexibility inherent in its implementation and analysis can undermine its validity. To test whether the TAP was a valid aggression measure irrespective of this flexibility, I conducted a preregistered study of a 25-trial version of the TAP using a single scoring approach with 160 diverse undergraduate participants. TAP scores showed agreement with other laboratory aggression measures and were magnified by an experimental provocation manipulation. Mixed evidence was found for associations with aggressive dispositions and real-world violence. These results provide preliminary support for this approach to the TAP to measure state-level aggressive behavior. However, more evidence is needed to assess the TAP’s external validity and ability to measure dispositional forms of aggression. Using preregistered designs, researchers should validate specific variants of their behavioral tasks in order to optimize the veridicality and reproducibility of psychological science.

scholarly journals POS1121 DEMOGRAPHICS, COMORBIDITIES, AND RENAL FUNCTION OF UNCONTROLLED GOUT PATIENTS WHO RECEIVED PEGLOTICASE: FINDING FROM A LARGE US CLAIMS DATABASE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 839.2-840
Author(s):  
C. Vesel ◽  
A. Morton ◽  
M. Francis-Sedlak ◽  
B. Lamoreaux
Keyword(s):  
Kidney Function ◽  
Real World ◽  
Randomized Clinical Trials ◽  
Small Subset ◽  
Phase 3 ◽  
Claims Database ◽  
Medical Diagnoses ◽  
Ckd Stage ◽  
Before And After ◽  
The Impact

Background:NHANES data indicate that approximately 9.2 million Americans have gout,1 with a small subset having uncontrolled disease.2 Pegloticase is a PEGylated recombinant uricase enzyme indicated for treating uncontrolled gout that markedly reduces serum uric acid levels (sUA)3 and resolves tophi in treatment responders.4 Despite pegloticase availability in the US for many years, real world demographics of pegloticase users in the treatment of uncontrolled gout have not been previously reported in a population-based cohort.Objectives:This study utilized a large US claims database to examine demographics and co-morbidities of uncontrolled gout patients treated with pegloticase. Kidney function before and after pegloticase treatment and concomitant therapy with immunomodulators were also examined.Methods:The TriNetX Diamond database includes de-identified data from 4.3 million US patients with gout (as of September 2019), including demographics, medical diagnoses, laboratory values, procedures (e.g. infusions, surgeries), and pharmacy data. Patients who had received ≥1 pegloticase infusion were included in these analyses. The number of infusions was evaluated for a subgroup of patients who were in the database ≥3 months before and ≥2 years after the first pegloticase infusion (i.e. first infusion prior to September 2017) to ensure only complete courses of therapy were captured. In this subpopulation, kidney function before and after pegloticase therapy was examined, along with the presence of immunomodulation prescriptions (methotrexate, mycophenolate mofetil, azathioprine, leflunomide) within 60 days prior to and 14 days after the first pegloticase infusion.Results:1494 patients treated with pegloticase were identified. Patients were 63.1 ± 14.0 years of age (range: 23–91), mostly male (82%), and white (76%). Mean sUA prior to pegloticase was 8.7 ± 2.4 mg/dL (n=50), indicating uncontrolled gout in the identified population. The most commonly reported comorbidities were chronic kidney disease (CKD, 48%), essential hypertension (71%), type 2 diabetes (39%), and cardiovascular disease (38%), similar to pegloticase pivotal Phase 3 trial populations. In patients with pre-therapy kidney function measures (n=134), pre-treatment eGFR averaged 61.2 ± 25.7 ml/min/1.73 m2, with 44% having Stage 3-5 CKD. In patients with complete therapy course capture and pre- and post-therapy eGFR measures (n=48), kidney function remained stable (change in eGFR: -2.9 ± 18.2 ml/min/1.73 m2) and CKD stage remained the same or improved in 81% of patients. In 791 patients with complete treatment course capture, patients had received 8.7 ± 13.8 infusions (median: 3, IQR: 2-10). Of these, 189 (24%) patients received only 1 pegloticase infusion and 173 (22%) received ≥12 infusions. As the data cut-off for this analysis pre-dated emerging data on the use of immunomodulation as co-therapy, only 19 of 791 (2%) patients received immunomodulation co-therapy with pegloticase.Conclusion:This relatively large group of patients with uncontrolled gout treated with pegloticase had similar patient characteristics of those studied in the phase 3 randomized clinical trials. Patients with uncontrolled gout are significantly burdened with systemic co-morbid diseases. The majority of patients had stable or improved kidney function following pegloticase treatment. As these results reflect patients initiating treatment prior to 2018, before co-treatment with immunomodulation was introduced, this cohort only included a small percentage of patients who were co-treated with an immunomodulator. Future studies using more current datasets are needed to evaluate real world outcomes in patients treated with pegloticase/immunomodulator co-therapy and to evaluate the impact of systemic co-morbid diseases.References:[1]Chen-Xu M, et al. Arthritis Rheumatol 2019 71:991-999.[2]Fels E, Sundy JS. Curr Opin Rheumatol 2008;20:198-202.[3]Sundy J, et al. JAMA 2011;306:711-720.[4]Mandell BF, et al. Arthritis Res Ther 2018;20:286.Disclosure of Interests:Claudia Vesel Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc, Allan Morton Speakers bureau: Sanofi, Amgen, and Horizon, Megan Francis-Sedlak Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc, Brian LaMoreaux Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc.

Improving the External Validity of Conjoint Analysis: The Essential Role of Profile Distribution

2021 ◽  
pp. 1-27 ◽  
Author(s):  
Brandon de la Cuesta ◽  
Naoki Egami ◽  
Kosuke Imai
Keyword(s):  
Conjoint Analysis ◽  
Real World ◽  
External Validity ◽  
Causal Effect ◽  
The Other ◽  
Estimation Methods ◽  
Social Scientists ◽  
Actual Distribution ◽  
Open Source Software Package ◽  
Profile Distribution

Abstract Conjoint analysis has become popular among social scientists for measuring multidimensional preferences. When analyzing such experiments, researchers often focus on the average marginal component effect (AMCE), which represents the causal effect of a single profile attribute while averaging over the remaining attributes. What has been overlooked, however, is the fact that the AMCE critically relies upon the distribution of the other attributes used for the averaging. Although most experiments employ the uniform distribution, which equally weights each profile, both the actual distribution of profiles in the real world and the distribution of theoretical interest are often far from uniform. This mismatch can severely compromise the external validity of conjoint analysis. We empirically demonstrate that estimates of the AMCE can be substantially different when averaging over the target profile distribution instead of uniform. We propose new experimental designs and estimation methods that incorporate substantive knowledge about the profile distribution. We illustrate our methodology through two empirical applications, one using a real-world distribution and the other based on a counterfactual distribution motivated by a theoretical consideration. The proposed methodology is implemented through an open-source software package.

scholarly journals Monoclonal Antibodies Targeting CGRP: From Clinical Studies to Real-World Evidence—What Do We Know So Far?

2021 ◽  
Vol 14 (7) ◽  
pp. 700
Author(s):  
Theodoros Mavridis ◽  
Christina I. Deligianni ◽  
Georgios Karagiorgis ◽  
Ariadne Daponte ◽  
Marianthi Breza ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Real World ◽  
Large Scale ◽  
Randomized Clinical Trials ◽  
Clinical Investigation ◽  
Phase Iii ◽  
Real World Evidence ◽  
Symptomatic Management ◽  
Repurposed Drugs ◽  
Cephalic Pain

Now more than ever is the time of monoclonal antibody use in neurology. In headaches, disease-specific and mechanism-based treatments existed only for symptomatic management of migraines (i.e., triptans), while the standard prophylactic anti-migraine treatments consist of non-specific and repurposed drugs that share limited safety profiles and high risk for interactions with other medications, resulting in rundown adherence rates. Recent advances in headache science have increased our understanding of the role of calcitonin gene relate peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) pathways in cephalic pain neurotransmission and peripheral or central sensitization, leading to the development of monoclonal antibodies (mAbs) or small molecules targeting these neuropeptides or their receptors. Large scale randomized clinical trials confirmed that inhibition of the CGRP system attenuates migraine, while the PACAP mediated nociception is still under scientific and clinical investigation. In this review, we provide the latest clinical evidence for the use of anti-CGRP in migraine prevention with emphasis on efficacy and safety outcomes from Phase III and real-world studies.

scholarly journals Multicenter, Observational Study of Lanreotide Autogel for the Treatment of Patients with Acromegaly in Routine Clinical Practice in Germany, Austria and Switzerland

2020 ◽  
Author(s):  
Sylvère Störmann ◽  
Jochen Schopohl ◽  
Catharina Bullmann ◽  
Christoph Terkamp ◽  
Mirjam Christ-Crain ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Growth Hormone ◽  
Growth Factor ◽  
Real World ◽  
Insulin Like Growth Factor ◽  
Biochemical Control ◽  
Factor I ◽  
Lanreotide Autogel

Abstract Background Evidence from controlled trials has shown that lanreotide autogel is effective in achieving biochemical and symptom control in patients with acromegaly. However, it is important to better understand the real-world patient population receiving lanreotide autogel treatment. Methods In this non-interventional study the long-term treatment response to lanreotide autogel in adult patients with acromegaly from office-based centers or clinics in Germany, Austria and Switzerland was studied. Assessments included growth hormone and insulin-like growth factor-I levels, symptoms, quality of life, lanreotide plasma levels and tumor somatostatin receptor subtype expression. The primary endpoint was achievement of full biochemical control, defined as growth hormone ≤2.5 µg/L and insulin-like growth factor I normalization at month 12. Results 76 patients were enrolled from 21 sites. 7/51 (13.7%) patients of the efficacy population had full biochemical control at baseline, 15/33 (45.5%) at month 12 and 10/26 (38.5%) at month 24 of treatment. At 12 months of treatment higher rates of biochemical control were observed in the following subgroups: older patients (>53 years [median]), females, treatment-naïve patients, and patients with a time since diagnosis of longer than 1.4 years (median). No clinically relevant differences in acromegaly symptoms or quality of life scores were observed. Median fasting blood glucose and glycated hemoglobin levels remained unchanged throughout the study. No new safety signals were observed. Overall tolerability of treatment with lanreotide autogel was judged by 80.8% of the enrolled patients at month 12 as ‘very good’ or ‘good’. Conclusion Treatment with lanreotide autogel in a real-world setting showed long-term effectiveness and good tolerability in patients with acromegaly.

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