scholarly journals SO093LONGITUDINAL DATA ON TREATMENT DURATION AND COMPLIANCE FROM AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE CLINICAL TRIALS WITH TOLVAPTAN

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Xiaolei Zhou ◽  
Diana Garbinsky ◽  
John Ouyang ◽  
Eric Davenport ◽  
Indra Agarwal ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Treatment Duration ◽  
Treatment Time ◽  
Treatment Compliance ◽  
Kidney Volume ◽  
Total Kidney Volume ◽  
Treatment Gaps ◽  
Clinical Trial Program

Abstract Background and Aims : Observation of impactful clinical outcomes in a clinical trial setting for ADPKD is challenging due to the life-long progressive nature of ADPKD and longer-term associated outcomes of interest in this population (e.g., renal function decline, cardiovascular events, and mortality). Since 2004, the tolvaptan (TOL) clinical trial program enrolled subjects in multiple clinical studies with the opportunity to enroll in subsequent clinical trials for treatment and outcomes evaluation. Method : Data from 6 ADPKD studies (protocols 156-04-250, 156-04-251, 156-06-260, 156-09-284, 156-09-290, 156-08-271) were pooled and evaluated over time for overall treatment duration, treatment time, and treatment gaps. Treatment duration for the individual clinical trials ranged from 1 week to up to 3 years. Results : Overall, 1,437 subjects received TOL in these ADPKD clinical trials. For these subjects, the mean overall treatment duration was 4.1 years (3.8 years on treatment) with a maximum of 9.7 years (9.0 years on treatment). In this cohort, 513 subjects (35.7%) received TOL treatment for more than 5 years. Mean treatment compliance was 94.1%. Overall, 723 subjects (50.3%) received TOL treatment in ≥2 trials, with a median treatment gap duration between trials of 0.1 years (maximum, 5.6 years). At least 7 years of follow-up data are available for estimated glomerular filtration rate in 241 subjects (mean at baseline, 78.6 mL/min/1.73m2) and for total kidney volume in 130 subjects (mean at baseline, 1,816.9 mL). Conclusion : This analysis provides longitudinal follow-up over an extended timeframe in a large number of subjects treated with TOL, with the greatest number of subjects being enrolled in clinical trials enriched for rapidly progressing ADPKD. Treatment compliance over years was reasonably good despite treatment gaps.

Patients with shoulder pain referred to specialist care; treatment, predictors of pain and disability, emotional distress, main symptoms and sick-leave: a cohort study with a six-months follow-up

2020 ◽  
Vol 20 (4) ◽  
pp. 775-783
Author(s):  
Kaia B. Engebretsen ◽  
Jens Ivar Brox ◽  
Niels Gunnar Juel
Keyword(s):  
Clinical Trials ◽  
Cohort Study ◽  
Sick Leave ◽  
Shoulder Pain ◽  
Emotional Distress ◽  
Outpatient Clinic ◽  
Treatment Duration ◽  
Specialist Care ◽  
Yellow Flags

AbstractObjectivesRecommendations for referral of patients with shoulder pain from primary to specialist care are mainly clinical. Several patients are referred without meeting these criteria for referral, whereas some are referred for a second opinion although surgery is not recommended. The aims of this study were to describe a shoulder pain cohort in specialist healthcare according to demographic data, clinical, and psychological factors; evaluate changes in pain and disability, distress and main symptoms from baseline to six-month follow-up; and to assess predictors of pain and disability, changes in the main symptoms and sick-leave at six-months. Results were compared to previous randomised trials conducted at the same clinic in patients with subacromial shoulder pain.MethodsThis prospective study included 167 patients from an outpatient clinic in specialist healthcare with shoulder pain for more than 6 weeks. Clinical (pain duration, intensity, pain sites), sociodemographic (age, gender, educational level, work status) and psychological variables (emotional distress (HSCL-10), fear of pain, screening of “yellow flags”, health-related quality of life) were collected. Shoulder pain and disability (SPADI-score) were assessed and the patients were asked about their outcome expectation and to predict their status of their shoulder problem the next month. They underwent a clinical interview, a clinical assessment of shoulder function and orthopaedic tests for diagnostic purposes. After six months they received a questionnaire with main variables.ResultsOf the 167 patients (55% women), 50% had symptoms for more than 12 months and 37 (22%) were on sick-leave. Characteristics were in general comparable to patients previously included in clinical trials at the same department. The SPADI-score was 46 (23) points. Mean emotional distress was within the normal range (1.7 (SD 0.6)). More than 80% had received treatment before, mainly physiotherapy in addition to the GPs treatment. One hundred and thirty-seven patients (82%) were re-referred to physiotherapy, 74 (44%) in the outpatient clinic specialist healthcare, and 63 (38%) in primary care. One hundred and eighteen (71%) answered the follow-up questionnaire. Mean change in SPADI-score was 10.5 points (95% CI (6.5–14.5)), and 29% of the patients improved more than the smallest detectable difference (SDD). The percentage sick-listed was 19.5%, and mean change in main symptoms (−9 to +9) was 3.4 (SD 3.9). The subgroup of patients receiving physiotherapy in outpatient specialist care did not show any significant change in the main variables. The prediction models suggested that a lower level of education, more fear of pain and a high baseline SPADI-score, predicted a higher SPADI-score at follow-up. A high baseline HSCL-10 score was the only significant predictor for a high HSCL-10 score. At follow-up, less pain at rest predicted more change in main symptoms and more yellow flags (a higher score on the Örebro screening test) predicted sick-leave.ConclusionsWithin the limitations of a cohort study, patients with persistent shoulder pain referred to an outpatient specialist clinic had similar baseline characteristics but shorter treatment duration, inferior clinical results and predictors somewhat different compared with previous clinical trials conducted at the same clinic. The study raises some questions about the effectiveness of the routines in daily clinical practice, the selection of patients, the treatment duration and content.

scholarly journals Urine and Plasma Osmolality in Patients with Autosomal Dominant Polycystic Kidney Disease: Reliable Indicators of Vasopressin Activity and Disease Prognosis?

2015 ◽  
Vol 41 (3) ◽  
pp. 248-256 ◽  
Author(s):  
Niek F. Casteleijn ◽  
Debbie Zittema ◽  
Stephan J.L. Bakker ◽  
Wendy E. Boertien ◽  
Carlo A. Gaillard ◽  
...  
Keyword(s):  
Water Intake ◽  
Plasma Osmolality ◽  
Urine Osmolality ◽  
Kidney Volume ◽  
Polycystic Kidney ◽  
Estimated Gfr ◽  
Total Kidney Volume ◽  
Autosomal Dominant Polycystic Kidney ◽  
Crude Analysis

Background: Vasopressin plays an essential role in osmoregulation, but has deleterious effects in patients with ADPKD. Increased water intake to suppress vasopressin activity has been suggested as a potential renoprotective strategy. This study investigated whether urine and plasma osmolality can be used as reflection of vasopressin activity in ADPKD patients. Methods: We measured urine and plasma osmolality, plasma copeptin concentration, total kidney volume (TKV, by MRI) and GFR (125I-iothalamate). In addition, change in estimated GFR (eGFR) during follow-up was assessed. Results: Ninety-four patients with ADPKD were included (56 males, age 40 ± 10, mGFR 77 ± 32 ml/min/1.73 m2, TKV 1.55 (0.99-2.40) l. Urine osmolality, plasma osmolality and copeptin concentration were 420 ± 195, 289 ± 7 mOsmol/l and 7.3 (3.2-14.6) pmol/l, respectively. Plasma osmolality was associated with copeptin concentration (R = 0.54, p < 0.001), whereas urine osmolality was not (p = 0.4). In addition, urine osmolality was not associated with TKV (p = 0.3), in contrast to plasma osmolality (R = 0.52, p < 0.001) and copeptin concentration (R = 0.61, p < 0.001). Fifty-five patients were followed for 2.8 ± 0.8 years. Baseline plasma and urine osmolality were not associated with change in eGFR (p = 0.6 and p = 0.3, respectively), whereas baseline copeptin concentration did show an association with change in eGFR, in a crude analysis (St. β = -0.41, p = 0.003) and also after adjustment for age, sex and TKV (St. β = -0.23, p = 0.05). Conclusions: These data suggest that neither urine nor plasma osmolality are valid measures to identify ADPKD patients that may benefit from increasing water intake. Copeptin appears a better alternative for this purpose.

Dedicated clinical trial tissue tracking database to improve turn-around time at high-volume center.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1543-1543
Author(s):  
Peter Blankenship ◽  
David DeLaRosa ◽  
Marc Burris ◽  
Steven Cusson ◽  
Kayla Hendricks ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Tissue Sample ◽  
High Volume ◽  
Trial Participation ◽  
Fresh Tissue ◽  
Oncology Clinical Trials ◽  
The Status ◽  
Unique Source

1543 Background: Tissue requirements in oncology clinical trials are increasingly complex due to prescreening protocols for patient selection and serial biopsies to understand molecular-level treatment effects. Novel solutions for tissue processing are necessary for timely tissue procurement. Based on these needs, we developed a Tissue Tracker (TT), a comprehensive database for study-related tissue tasks at our high-volume clinical trial center. Methods: In this Microsoft Access database, patients are assigned an ID within the TT that is associated with their name, medical record number, and study that follows their request to external users: pathology departments, clinical trial coordinators and data team members. To complete tasks in the TT, relevant information is required to update the status. Due to the high number of archival tissue requests from unique pathology labs, the TT has a “Follow-Up Dashboard” that organizes information needed to conduct follow-up on all archival samples with the status “Requested”. This results in an autogenerated email and pdf report sent to necessary teams. The TT also includes a kit inventory system and a real-time read only version formatted for interdepartmental communication, metric reporting, and other data-driven efforts. The primary outcome in this study was to evaluate our average turnaround time (ATAT: average time from request to shipment) for archival and fresh tissue samples before and after TT development. Results: Before implementing the TT, between March 2016 and March 2018, we processed 2676 archival requests from 235 unique source labs resulting in 2040 shipments with an ATAT of 19.29 days. We also processed 1099 fresh biopsies resulting in 944 shipments with an ATAT of 7.72 days. After TT implementation, between April 2018 and April 2020, we processed 2664 archival requests from 204 unique source labs resulting in 2506 shipments (+28.0%) with an ATAT of 14.78 days (-23.4%). During that same period, we processed 1795 fresh biopsies (+63.3%) resulting in 2006 shipments (+112.5%) with an ATAT of 6.85 days (-11.3%). Conclusions: Oncology clinical trials continue to evolve toward more extensive tissue requirements for prescreening and scientific exploration of on-treatment molecular profiling. Timely results are required to optimize patient trial participation. During the intervention period, our tissue sample volume and shipments increased, but the development and implementation of an automated tracking system allowed improvement in ATAT of both archival and fresh tissue. This automation not only improves end-user expectations and experiences for patients and trial sponsors but this allows our team to adapt to the increasing interest in tissue exploration.

scholarly journals Results availability and timeliness of registered COVID-19 clinical trials: interim cross-sectional results from the DIRECCT study

BMJ Open ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. e053096
Author(s):  
Maia Salholz-Hillel ◽  
Peter Grabitz ◽  
Molly Pugh-Jones ◽  
Daniel Strech ◽  
Nicholas J DeVito
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Journal Article ◽  
Cross Sectional Study ◽  
Sensitivity Analyses ◽  
Cross Sectional ◽  
Registration Data ◽  
Clinical Trial Registries ◽  
Treatment And Prevention

ObjectiveTo examine how and when the results of COVID-19 clinical trials are disseminated.DesignCross-sectional study.SettingThe COVID-19 clinical trial landscape.Participants285 registered interventional clinical trials for the treatment and prevention of COVID-19 completed by 30 June 2020.Main outcome measuresOverall reporting and reporting by dissemination route (ie, by journal article, preprint or results on a registry); time to reporting by dissemination route.ResultsFollowing automated and manual searches of the COVID-19 literature, we located 41 trials (14%) with results spread across 47 individual results publications published by 15 August 2020. The most common dissemination route was preprints (n=25) followed by journal articles (n=18), and results on a registry (n=2). Of these, four trials were available as both a preprint and journal publication. The cumulative incidence of any reporting surpassed 20% at 119 days from completion. Sensitivity analyses using alternate dates and definitions of results did not appreciably change the reporting percentage. Expanding minimum follow-up time to 3 months increased the overall reporting percentage to 19%.ConclusionCOVID-19 trials completed during the first 6 months of the pandemic did not consistently yield rapid results in the literature or on clinical trial registries. Our findings suggest that the COVID-19 response may be seeing quicker results disclosure compared with non-emergency conditions. Issues with the reliability and timeliness of trial registration data may impact our estimates. Ensuring registry data are accurate should be a priority for the research community during a pandemic. Data collection is underway for the next phase of the DIssemination of REgistered COVID-19 Clinical Trials study expanding both our trial population and follow-up time.

Adaptive Learning of Drug Quality and Optimization of Patient Recruitment for Clinical Trials with Dropouts

2021 ◽  
Author(s):  
Zhili Tian ◽  
Weidong Han ◽  
Warren B. Powell
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Dynamic Programming ◽  
Value Function ◽  
Standard Treatment ◽  
Treatment Effectiveness ◽  
Interim Analyses ◽  
Clinical Trial Program ◽  
Patient Enrollment ◽  
The Value Function

Problem definition: Clinical trials are crucial to new drug development. This study investigates optimal patient enrollment in clinical trials with interim analyses, which are analyses of treatment responses from patients at intermediate points. Our model considers uncertainties in patient enrollment and drug treatment effectiveness. We consider the benefits of completing a trial early and the cost of accelerating a trial by maximizing the net present value of drug cumulative profit. Academic/practical relevance: Clinical trials frequently account for the largest cost in drug development, and patient enrollment is an important problem in trial management. Our study develops a dynamic program, accurately capturing the dynamics of the problem, to optimize patient enrollment while learning the treatment effectiveness of an investigated drug. Methodology: The model explicitly captures both the physical state (enrolled patients) and belief states about the effectiveness of the investigated drug and a standard treatment drug. Using Bayesian updates and dynamic programming, we establish monotonicity of the value function in state variables and characterize an optimal enrollment policy. We also introduce, for the first time, the use of backward approximate dynamic programming (ADP) for this problem class. We illustrate the findings using a clinical trial program from a leading firm. Our study performs sensitivity analyses of the input parameters on the optimal enrollment policy. Results: The value function is monotonic in cumulative patient enrollment and the average responses of treatment for the investigated drug and standard treatment drug. The optimal enrollment policy is nondecreasing in the average response from patients using the investigated drug and is nonincreasing in cumulative patient enrollment in periods between two successive interim analyses. The forward ADP algorithm (or backward ADP algorithm) exploiting the monotonicity of the value function reduced the run time from 1.5 months using the exact method to a day (or 20 minutes) within 4% of the exact method. Through an application to a leading firm’s clinical trial program, the study demonstrates that the firm can have a sizable gain of drug profit following the optimal policy that our model provides. Managerial implications: We developed a new model for improving the management of clinical trials. Our study provides insights of an optimal policy and insights into the sensitivity of value function to the dropout rate and prior probability distribution. A firm can have a sizable gain in the drug’s profit by managing its trials using the optimal policies and the properties of value function. We illustrated that firms can use the ADP algorithms to develop their patient enrollment strategies.

scholarly journals Patients with cancer in the COVID-19 era: the clinical trial issue

2020 ◽  
Vol 106 (4) ◽  
pp. 271-272 ◽  
Author(s):  
Marcello Scarcia ◽  
Giuseppe Mario Ludovico ◽  
Angela Fortunato ◽  
Alba Fiorentino
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Physical Examination ◽  
Regulatory Agencies ◽  
Study Medication ◽  
Therapeutic Modalities ◽  
Patients With Cancer ◽  
Safety Guidelines ◽  
Trial Discontinuation

Coronavirus disease 2019 (COVID-19) hospital reorganization may result in reduced ability for the hospital to fully use its armamentarium for battling cancer. Thus different therapeutic modalities have been recommended. During the pandemic, despite regulatory agencies’ recommendations, several considerations and doubts remain for oncologic clinical trials. Considering patients who had been enrolled before the pandemic, and who plan to take the study medication, the situation becomes complicated. These patients should undergo monitoring visits, blood sampling, questionnaire, physical examination, and drug and radiation administration. To avoid deviations from the protocol and trial discontinuation, follow-up should be performed regularly, in concordance with safety guidelines. Here we report several considerations.

scholarly journals Parental perspectives long term after neonatal clinical trial participation: a survey

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Thomas Salaets ◽  
Emilie Lavrysen ◽  
Anne Smits ◽  
Sophie Vanhaesebrouck ◽  
Maissa Rayyan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Trial Participation ◽  
Drug Trials ◽  
Clinical Trial Participation ◽  
Parental Perspectives ◽  
Positive Experiences ◽  
Almost All

Abstract Background Although recruiting newborns is ethically challenging, clinical trials remain essential to improve neonatal care. There is a lack of empirical data on the parental perspectives following participation of their neonate in a clinical trial, especially at long term. The objective of this study is to assess experiences and emotions of parents, long term after trial participation in an interventional drug trial. Methods Parents of former participants of five neonatal interventional drug trials were surveyed at long term (3–13 years ago) after participation. The survey assessed parental contentment with trial participation, perceived influence of the trial on care and health, emotional consequences of participation, and awareness of typical clinical trial characteristics on 6-point Likert scales. Results Complete responses were received from 123 parents (52% of involved families). Twenty percent of parents did not remember participation. Those who remembered participation reported high contentment with overall trial participation (median 5.00), but not with follow-up (median 3.00). Most parents did not perceive any influence of the trial on care (median 2.00) and health (median 2.43). Almost all parents reported satisfaction and pride (median 4.40), while a minority of parents reported anxiety and stress (median 1.44) or guilt (median 1.33) related to trial participation. A relevant minority was unaware of typical trial characteristics (median 4.20; 27% being unaware). Conclusions Overall, parents reported positive experiences and little emotional distress long term after participation. Future efforts to improve the practice of neonatal clinical trials should focus on ensuring effective communication about the concept and characteristics of a clinical trial during consent discussions and on the follow-up after the trial.

Adverse Reactions following Two Separate Intravascular Injections of Contrast Media in the Same Patient

1987 ◽  
Vol 28 (1) ◽  
pp. 93-97 ◽  
Author(s):  
E. E. Sogn ◽  
T. Ødegård ◽  
T. Haider ◽  
E. Andrew
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Contrast Media ◽  
Contrast Medium ◽  
Comparative Studies ◽  
Adverse Reactions ◽  
Northern Europe ◽  
Retrospective Design ◽  
Clinical Trial Program ◽  
Recurrence Frequency

Adverse reactions following contrast medium injections in 26 non-comparative and parallel trials were extracted from the iohexol vascular clinical trial program in Northern Europe. Six hundred and forty-one patients (13–88 years old) in whom information was available about a vascular contrast medium examination before the iohexol clinical trials were included, enabling a retrospective within patient comparison of adverse reactions. Iohexol gave a lower recurrence frequency (approximately 3.5 times) of reactions than ionic monomers in patients who previously experienced adverse reactions to vascular contrast media. In order to overcome some of the drawbacks with the present retrospective design, prospective comparative studies are recommended.

scholarly journals Safety Profile of Immunotherapy Combined With Antiangiogenic Therapy in Patients With Melanoma: Analysis of Three Clinical Studies

2021 ◽  
Vol 12 ◽  
Author(s):  
Hui Tian ◽  
Xuan Wang ◽  
Bin Lian ◽  
Xieqiao Yan ◽  
Lu Si ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Event ◽  
Treatment Duration ◽  
Retrospective Cohort ◽  
Regression Models ◽  
Antiangiogenic Therapy ◽  
Risk Models ◽  
Clinical Trial Registration ◽  
Logistic Regression Models

Objective: To describe the frequency and spectrum of treatment-related adverse events (TRAEs) of immunotherapy combined with antiangiogenic therapy in patients with melanoma.Methods: This retrospective cohort study included three clinical trials on patients with stage III/IV melanoma treated with anti–PD 1 and antiangiogenic therapy.Results: We analyzed data from 72 patients with a median follow-up time of 25.9 months (95% CI, 9.1–42.7 m). The median treatment duration was 7.5 months (range, 0.7–42.8 m), and the median of treatment cycles was 11.0 (range, 1–90). Most patients (70 of 72 or 97.2%) experienced TRAEs (mostly grades 1 or 2). No drug-related deaths were reported. Most TRAEs were hepatic (75%), endocrine (72.2%), skin (65.3%), and gastrointestinal tract (59.7%) manifestations, followed by myelosuppression (55.6%), renal dysfunction (55.6%), and dyslipidaemia (54.2%). The adverse event (AE) spectra were similar between regimens. Using multivariate Cox proportional risk models showed that hypertension was associated with a long PFS. According to our multivariable logistic regression models, TRAEs were not associated with ORR.Conclusion: We found that the prevalence of AEs was higher than that of anti–PD-1 monotherapy. Most of the AEs were mild. The AE spectra were similar to those seen after anti–PD-1 or antiangiogenic therapy monotherapy, without unexpected AEs. Immunotherapy combined with antiangiogenic therapy was well tolerated.Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03955354.

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