scholarly journals Use of routinely collected health data in randomised clinical trials: comparison of trial-specific death data in the BOSS trial with NHS Digital data

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sharon B. Love ◽  
Anna Kilanowski ◽  
Victoria Yorke-Edwards ◽  
Oliver Old ◽  
Hugh Barr ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Oesophageal Cancer ◽  
Health Data ◽  
Digital Data ◽  
Phase Iii ◽  
Specific Data ◽  
Routinely Collected Health Data ◽  
Death Data

Abstract Background A promising approach to reduce the increasing costs of clinical trials is the use of routinely collected health data as participant data. However, the quality of this data could limit its usability as trial participant data. Methods The BOSS trial is a randomised controlled trial comparing regular endoscopies versus endoscopies at need in patients with Barrett’s oesophagus with primary endpoint death. Data on death and cancer collected every 2 years after randomisation (trial-specific data) were compared to data received annually (all patients on one date) from the routinely collected health data source National Health Service (NHS) Digital. We investigated completeness, agreement and timeliness and looked at the implications for the primary trial outcome. Completeness and agreement were assessed by evaluating the number of reported and missing cases and any disparities between reported dates. Timeliness was considered by graphing the year a death was first reported in the trial-specific data against that for NHS Digital data. Implications on the primary trial outcome, overall survival, of using one of the data sources alone were investigated using Kaplan-Meier graphs. To assess the utility of cause of death and cancer diagnoses, oesophageal cancer cases were compared. Results NHS Digital datasets included more deaths and often reported them sooner than the trial-specific data. The number reported as being from oesophageal cancer was similar in both datasets. Due to time lag in reporting and missing cases, the event rate appeared higher using the NHS Digital data. Conclusion NHS Digital death data is useful for calculating overall survival where trial-specific follow-up is only every 2 years from randomisation and the follow-up requires patient response. The cancer data was not a large enough sample to assess usability. We suggest that this assessment of registry data is done for more phase III RCTs and for more registry data to get a more complete picture of when RCHD would be useful in phase III RCT. Trial registration ISRCTN54190466 (BOSS) 1 Oct 2009.

scholarly journals Use of Routinely Collected Health Data in Randomised Clinical Trials: Comparison of Trial-Specific Death Data in The BOSS Trial with NHS Digital Data

2020 ◽  
Author(s):  
Sharon Love ◽  
Anna Kilanowski ◽  
Victoria Yorke-Edwards ◽  
Oliver Old ◽  
Hugh Barr ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Health Data ◽  
Digital Data ◽  
Phase Iii ◽  
Specific Data ◽  
Routinely Collected Health Data ◽  
Data Source ◽  
Death Data

Abstract Background: A promising approach to reduce the increasing costs of clinical trials is the use of routinely-collected health data as participant data. However, the quality of this data could limit it’s usability as trial participant data. Methods: The BOSS trial is an RCT comparing regular endoscopies versus endoscopies at need in patients with Barrett’s oesophagus with primary endpoint death. Data on death and cancer collected every 2 years after randomisation (trial-specific data) were compared to data received annually (all patients on one date) from the routinely-collected health data source NHS Digital. We investigated completeness, agreement, timeliness and looked at the implications for the primary trial outcome. Completeness and agreement were assessed by evaluating the number of reported and missing cases and any disparities between reported dates. Timeliness was considered by graphing the year a death was first reported in the trial specific data against that for NHS Digital data. Implications on the primary trial outcome, overall survival, of using one of the data source alone were investigated using Kaplan-Meier graphs. To assess utility of cause of death and cancer diagnoses, oesophageal cancer cases were compared.Results: NHS Digital datasets included more deaths and often reported them sooner than the trial-specific data. The number reported as being from oesophageal cancer was similar in both datasets. Due to time lag in reporting and missing cases, the event rate appeared higher using the NHS Digital data. Conclusion: NHS Digital death data is useful for calculating overall survival where trial-specific follow-up is only every 2 years from randomisation and the follow-up requires patient response. The cancer data was not a large enough sample to assess usability. We suggest that this assessment of registry data is done for more phase III RCTs and for more registry data to get a more complete picture of when RCHD would be useful in phase III RCT.Trial registration: ISRCTN54190466 (BOSS)

Disease-Free Survival Versus Overall Survival As a Primary End Point for Adjuvant Colon Cancer Studies: Individual Patient Data From 20,898 Patients on 18 Randomized Trials

2005 ◽  
Vol 23 (34) ◽  
pp. 8664-8670 ◽  
Author(s):  
Daniel J. Sargent ◽  
Harry S. Wieand ◽  
Daniel G. Haller ◽  
Richard Gray ◽  
Jacqueline K. Benedetti ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Clinical Trials ◽  
Individual Patient Data ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
End Point ◽  
Disease Free

Purpose A traditional end point for colon adjuvant clinical trials is overall survival (OS), with 5 years demonstrating adequate follow-up. A shorter-term end point providing convincing evidence to allow treatment comparisons could significantly speed the translation of advances into practice. Methods Individual patient data were pooled from 18 randomized phase III colon cancer adjuvant clinical trials. Trials included 43 arms, with a pooled sample size of 20,898 patients. The primary hypothesis was that disease-free survival (DFS), with 3 years of follow-up, is an appropriate primary end point to replace OS with 5 years of follow-up. Results The recurrence rates for years 1 through 5 were 12%, 14%, 8%, 5%, and 3%, respectively. Median time from recurrence to death was 12 months. Eighty percent of recurrences were in the first 3 years; 91% of patients with recurrence by 3 years died before 5 years. Correlation between 3-year DFS and 5-year OS was 0.89. Comparing control versus experimental arms within each trial, the correlation between hazard ratios for DFS and OS was 0.92. Within-trial log-rank testing using both DFS and OS provided the same conclusion in 23 (92%) of 25 cases. Formal measures of surrogacy were satisfied. Conclusion In patients treated on phase III adjuvant colon clinical trials, DFS and OS are highly correlated, both within patients and across trials. These results suggest that DFS after 3 years of median follow-up is an appropriate end point for adjuvant colon cancer clinical trials of fluorouracil-based regimens, although marginally significant DFS improvements may not translate into significant OS benefits.

scholarly journals Access to routinely collected health data for clinical trials – review of successful data requests to UK registries

2020 ◽  
Author(s):  
Sarah Lensen ◽  
Archie Macnair ◽  
Sharon B Love ◽  
Victoria Yorke-Edwards ◽  
Nurulamin M Noor ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Data Extraction ◽  
Health Data ◽  
Lack Of Information ◽  
Routinely Collected Health Data ◽  
Long Term Follow Up ◽  
Randomised Controlled ◽  
The Uk

ABSTRACTBackgroundClinical trials generally each collect their own data despite routinely-collected health data (RCHD) increasing in quality and breadth. Our aim is to quantify UK-based randomised controlled trials (RCTs) accessing RCHD for participant data, characterise how these data are used and thereby recommend how more trials could use RCHD.MethodsWe conducted a systematic review of RCTs accessing RCHD from at least one registry in the UK between 2013-2018, for the purposes of informing or supplementing participant data. A list of all registries holding RCHD in the UK was compiled. In cases where registries published release registers, these were searched for RCTs accessing RCHD. Where no release register was available, registries were contacted to request a list of RCTs. For each identified RCT, information was collected from all publicly available sources (release registers, websites, protocol etc.). The search and data extraction was undertaken between Jan-2019 and May-2019.ResultsWe identified 160 RCTs accessing RCHD between 2013 and 2018 from a total of 22 registries; this corresponds to only a very small proportion of all UK RCTs (approximately 3%). RCTs accessing RCHD were generally large (median sample size 1590), commonly evaluating treatments for cancer or cardiovascular disease. Most of the included RCTs accessed RCHD from NHS Digital (68%), and the most frequently accessed datasets were mortality (76%) and hospital visits (55%). RCHD was used to inform the primary trial (82%) and long-term follow-up (57%). There was substantial variation in how RCTs used RCHD to inform participant outcome measures. A limitation was the lack of information and transparency from registries and RCTs with respect to which datasets have been accessed and for what purposes.ConclusionsIn the last five years, only a small minority of UK-based RCTs have accessed RCHD to inform participant data. We ask for improved accessibility, confirmed data quality and joined up thinking between the registries and the regulatory authorities.RegistrationPROSPERO CRD42019123088

Three-year follow-up of ATTRACTION-3: A phase III study of nivolumab (Nivo) in patients with advanced esophageal squamous cell carcinoma (ESCC) that is refractory or intolerant to previous chemotherapy.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 204-204
Author(s):  
Keisho Chin ◽  
Ken Kato ◽  
Byoung Chul Cho ◽  
Masanobu Takahashi ◽  
Morihito Okada ◽  
...  
Keyword(s):  
Overall Survival ◽  
Subgroup Analysis ◽  
Survival Data ◽  
Special Interest ◽  
Safety Data ◽  
Phase Iii ◽  
Taxane Chemotherapy ◽  
Favorable Safety ◽  
Safety Signals

204 Background: Previous results from the ATTRACTION-3 phase 3 trial demonstrated a significant improvement in overall survival and a favorable safety profile compared with taxane chemotherapy (CT) in previously-treated ESCC patients. To our knowledge, no long-term efficacy and safety data of this immune checkpoint inhibitor has been reported in ESCC. Herein, we report the three-year survival data of Nivo in ESCC. Methods: In ATTRACTION-3, 419 patients with unresectable advanced or recurrent ESCC refractory or intolerant to 1 prior fluoropyrimidine/platinum-based CT were randomized in a 1:1 ratio to receive Nivo (N = 210) or the investigator’s choice of CT (paclitaxel or docetaxel) (N = 209) until disease progression or unacceptable toxicity. The primary endpoint was overall survival (OS). A subgroup analysis of OS according to the best overall response (BOR) was performed. The onset of treatment-related adverse events of special interest over time in the Nivo arm was also evaluated. Results: As of data cut-off on 25 May 2020, 3 years after the last patient was enrolled, the median OS (mOS) was 10.91 months with Nivo versus 8.51 months with CT [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.64-0.97]. The OS rates of patients with Nivo and CT were 20.2 % and 13.5 % at 24 months, and 15.3% and 8.7% at 36 months, respectively. In the subgroup analysis of OS by BOR, mOS in CR/PR patients were 19.91 and 15.41 months (HR 0.84, 95%CI 0.46-1.54) and that in SD patients were 17.38 and 9.36 months (HR 0.45, 95%CI 0.26-0.78) in the Nivo and CT arm, respectively. Furthermore, mOS in PD patients were 10.91 and 6.18 months (HR 0.56, 95%CI 0.33-0.95) in the Nivo and CT arm, respectively. No new safety signals were detected during the three-year follow-up. Time to onset of the event of special interest was within the range of events previously observed in other indications. Conclusions: At three-year follow up, Nivo continued to show improved OS over CT in pretreated patients with advanced ESCC patients. Nivo showed a longer mOS than CT regardless of BOR. During the three-year follow-up, no new safety signals were observed. Clinical trial information: NCT02569242.

scholarly journals Association of Cardiovascular Risk Factors With Cardiac Events and Survival Outcomes Among Patients With Breast Cancer Enrolled in SWOG Clinical Trials

2018 ◽  
Vol 36 (26) ◽  
pp. 2710-2717 ◽  
Author(s):  
Dawn L. Hershman ◽  
Cathee Till ◽  
Sherry Shen ◽  
Jason D. Wright ◽  
Scott D. Ramsey ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cardiovascular Disease ◽  
Overall Survival ◽  
Clinical Trials ◽  
Survival Outcomes ◽  
Cardiac Events ◽  
Free Survival ◽  
Increased Risk

Background Cardiovascular disease is the primary cause of death among patients with breast cancer. However, the association of cardiovascular-disease risk factors (CVD-RFs) with long-term survival and cardiac events is not well studied. Methods We examined SWOG (formerly the Southwest Oncology Group) breast cancer trials from 1999 to 2011. We identified baseline diabetes, hypertension, hypercholesterolemia, and coronary artery disease by linking trial records to Medicare claims. The primary outcome was overall survival. Patients with both baseline and follow-up claims were examined for cardiac events. Cox regression was used to assess the association between CVD-RFs and outcomes. Results We identified 1,460 participants older than 66 years of age from five trials; 842 were eligible for survival outcomes analysis. At baseline, median age was 70 years, and median follow-up was 6 years. Hypertension (73%) and hypercholesterolemia (57%) were the most prevalent conditions; 87% of patients had one or more CVD-RF. There was no association between any of the individual CVD-RFs and overall survival except for hypercholesterolemia, which was associated with improved overall survival (hazard ratio [HR], 0.73; 95% CI, 0.57 to 0.93; P = .01). With each additional CVD-RF, there was an increased risk of death (HR, 1.23; 95% CI, 1.08 to 1.40; P = .002), worse progression-free survival (HR, 1.12; 95% CI, 1.00 to 1.25; P = .05), and marginally worse cancer-free survival (HR, 1.15; 95% CI, 0.99 to 1.34; P = .07). The relationship between baseline CVD-RFs and cardiac events was analyzed in 736 patients. A strong linear association between the number of CVD-RFs and cardiac event was observed (HR per CVD-RF, 1.41; 95% CI, 1.17 to 1.69; P < .001). Conclusion Among participants in clinical trials, each additional baseline CVD-RF was associated with an increased risk of cardiac events and death. Efforts to improve control of modifiable CVD-RFs are needed, especially among those with multiple risk factors.

Efficacy of Melphalan and Prednisone Plus Thalidomide in Patients Older Than 75 Years With Newly Diagnosed Multiple Myeloma: IFM 01/01 Trial

2009 ◽  
Vol 27 (22) ◽  
pp. 3664-3670 ◽  
Author(s):  
Cyrille Hulin ◽  
Thierry Facon ◽  
Philippe Rodon ◽  
Brigitte Pegourie ◽  
Lotfi Benboubker ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Elderly Patients ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Standards Of Care ◽  
Newly Diagnosed ◽  
Grade 3 ◽  
To Receive

Purpose Until recently, melphalan and prednisone were the standards of care in elderly patients with multiple myeloma. The addition of thalidomide to this combination demonstrated a survival benefit for patients age 65 to 75 years. This randomized, placebo-controlled, phase III trial investigated the efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed myeloma. Patients and Methods Between April 2002 and December 2006, 232 previously untreated patients with myeloma, age 75 years or older, were enrolled and 229 were randomly assigned to treatment. All patients received melphalan (0.2 mg/kg/d) plus prednisone (2 mg/kg/d) for 12 courses (day 1 to 4) every 6 weeks. Patients were randomly assigned to receive 100 mg/d of oral thalidomide (n = 113) or placebo (n = 116), continuously for 72 weeks. The primary end point was overall survival. Results After a median follow-up of 47.5 months, overall survival was significantly longer in patients who received melphalan and prednisone plus thalidomide compared with those who received melphalan and prednisone plus placebo (median, 44.0 v 29.1 months; P = .028). Progression-free survival was significantly prolonged in the melphalan and prednisone plus thalidomide group (median, 24.1 v 18.5 months; P = .001). Two adverse events were significantly increased in the melphalan and prednisone plus thalidomide group: grade 2 to 4 peripheral neuropathy (20% v 5% in the melphalan and prednisone plus placebo group; P < .001) and grade 3 to 4 neutropenia (23% v 9%; P = .003). Conclusion This trial confirms the superiority of the combination melphalan and prednisone plus thalidomide over melphalan and prednisone alone for prolonging survival in very elderly patients with newly diagnosed myeloma. Toxicity was acceptable.

Factors Affecting Workload of Cancer Clinical Trials: Results of a Multicenter Study of the National Cancer Institute of Canada Clinical Trials Group

2002 ◽  
Vol 20 (2) ◽  
pp. 545-556 ◽  
Author(s):  
Kathyrn Roche ◽  
Nancy Paul ◽  
Bobbi Smuck ◽  
Marlo Whitehead ◽  
Benny Zee ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Data Collection ◽  
Cancer Treatment ◽  
Multicenter Study ◽  
National Cancer Institute ◽  
Phase Iii ◽  
Study Phase ◽  
Factors Affecting ◽  
Clinical Research Associates

PURPOSE: Increasingly, cancer treatment centers need to be able to estimate specific costs and resources associated with clinical trials. Because the time requirements of trial coordination and data collection are not well known, the Clinical Research Associates (CRA) Committee of the National Cancer Institute of Canada Clinical Trials Group carried out a multicenter study to measure trials’ task times and evaluate the effects of certain factors. METHODS: A data collection instrument was designed and validated before its implementation in the study. Eighty-three CRAs from 24 cancer treatment institutions across Canada collected timing observations of 41 tasks (156 subtasks). Information from all stages of trials activity (protocol management, eligibility and entry, treatment, and follow-up and final stage) was obtained, from initial negotiations to follow-up after study closure. RESULTS: After controlling for stage, phase and sponsor were found to be significant independent factors. Analysis within the stages showed similar patterns. New drug inclusion as a factor was confounded with phase. Industry-sponsored studies had significantly higher overall mean times than did local and cooperative group studies. Early-phase studies required more time than did phase III trials. External sponsorship of any kind increased CRA time more than that necessary for locally coordinated studies, except during the protocol management stage. The burden of a phase I study increased to greater than average once underway and accruing patients. CONCLUSION: Our data demonstrated that sponsor and study phase are important factors to be taken into consideration when estimating clinical trial costs and resource use.

scholarly journals Final Results of the IELSG-19 Randomized Trial of Mucosa-Associated Lymphoid Tissue Lymphoma: Improved Event-Free and Progression-Free Survival With Rituximab Plus Chlorambucil Versus Either Chlorambucil or Rituximab Monotherapy

2017 ◽  
Vol 35 (17) ◽  
pp. 1905-1912 ◽  
Author(s):  
Emanuele Zucca ◽  
Annarita Conconi ◽  
Giovanni Martinelli ◽  
Reda Bouabdallah ◽  
Alessandra Tucci ◽  
...  
Keyword(s):  
Overall Survival ◽  
Randomized Trial ◽  
Lymphoid Tissue ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
Final Sample ◽  
Phase Iii Study ◽  
To Receive

Purpose There is no consensus on the optimal systemic treatment of patients with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The IELSG-19 phase III study, to our knowledge, was the first such study to address the question of first-line treatment in a randomized trial. Patients and Methods Eligible patients were initially randomly assigned (1:1 ratio) to receive either chlorambucil monotherapy (6 mg/m2/d orally on weeks 1 to 6, 9 to 10, 13 to 14, 17 to 18, and 21 to 22) or a combination of chlorambucil (same schedule as above) and rituximab (375 mg/m2 intravenously on day 1 of weeks 1, 2, 3, 4, 9, 13, 17, and 21). After the planned enrollment of 252 patients, the protocol was amended to continue with a three-arm design (1:1:6 ratio), with a new arm that included rituximab alone (same schedule as the combination arm) and with a final sample size of 454 patients. The main end point was event-free survival (EFS). Analysis of chlorambucil versus the combination arm was performed and reported separately before any analysis of the third arm. Results At a median follow-up of 7.4 years, addition of rituximab to chlorambucil led to significantly better EFS (hazard ratio, 0.54; 95% CI, 0.38 to 0.77). EFS at 5 years was 51% (95% CI, 42 to 60) with chlorambucil alone, 50% (95% CI, 42 to 59) with rituximab alone, and 68% (95% CI, 60 to 76) with the combination ( P = .0009). Progression-free survival was also significantly better with the combination ( P = .0119). Five-year overall survival was approximately 90% in each arm. All treatments were well tolerated. No unexpected toxicities were recorded. Conclusion Rituximab in combination with chlorambucil demonstrated superior efficacy in mucosa-associated lymphoid tissue lymphoma; however, improvements in EFS and progression-free survival did not translate into longer overall survival.

scholarly journals Continued Excellent Outcomes in Previously Untreated Patients With Follicular Lymphoma After Treatment With CHOP Plus Rituximab or CHOP Plus 131I-Tositumomab: Long-Term Follow-Up of Phase III Randomized Study SWOG-S0016

2018 ◽  
Vol 36 (7) ◽  
pp. 697-703 ◽  
Author(s):  
Mazyar Shadman ◽  
Hongli Li ◽  
Lisa Rimsza ◽  
John P. Leonard ◽  
Mark S. Kaminski ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Randomized Study ◽  
Phase Iii ◽  
Second Malignancies ◽  
Long Term Follow Up ◽  
Acute Myeloid

Purpose SWOG S0016 was a phase III randomized study that compared the safety and efficacy of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) with CHOP-RIT (CHOP followed by consolidation with iodine-133–tositumomab radioimmunotherapy) for previously untreated patients with follicular lymphoma. Understanding the long-term outcome of patients provides a benchmark for novel treatment regimens for FL. Patients and Methods Between 2001 and 2008, 531 previously untreated patients with FL were randomly assigned to receive either six cycles of R-CHOP or six cycles of CHOP-RIT. Patients with advanced-stage disease (bulky stage II, III, or IV) of any pathologic grade (1, 2, or 3) were eligible. Results After a median follow-up of 10.3 years, 10-year estimates of progression-free and overall survival were 49% and 78% among all patients, respectively. Patients in the CHOP-RIT arm had significantly better 10-year progression-free survival compared with patients in the R-CHOP arm (56% v 42%; P = .01), but 10-year overall survival was not different between the two arms (75% v 81%; P = .13). There was no significant difference between the CHOP-RIT and R-CHOP arms in regard to incidence of second malignancies (15.1% v 16.1%; P = .81) or myelodysplastic syndrome or acute myeloid leukemia (4.9% v 1.8%; P = .058). The estimated 10-year cumulative incidences of death resulting from second malignancies were not different (7.1% v 3.2%; P = .16), but cumulative incidence of death resulting from myelodysplastic syndrome or acute myeloid leukemia was higher in the CHOP-RIT arm compared with the R-CHOP arm (4% v 0.9%; P = .02). Conclusion Given these outstanding outcomes, immunochemotherapy should remain the standard induction approach for patients with high-risk FL until long-term follow-up of alternative approaches demonstrates superiority.

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