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BMC Health Services Research Aug 2020There is both higher mortality and morbidity from cancer in low and medium income countries (LMICs) compared with high income countries (HICs). Clinical trial activities...
BACKGROUND
There is both higher mortality and morbidity from cancer in low and medium income countries (LMICs) compared with high income countries (HICs). Clinical trial activities and development of more effective and less toxic therapies have led to significant improvements in morbidity and mortality from cancer in HICs. Unfortunately, clinical trials remain low in LMICs due to poor infrastructure and paucity of experienced personnel to execute clinical trials. There is an urgent need to build local capacity for evidence-based treatment for cancer patients in LMICs.
METHODS
We conducted a survey at facilities in four Teaching Hospitals in South West Nigeria using a checklist of information on various aspects of clinical trial activities. The gaps identified were addressed using resources sourced in partnership with investigators at HIC institutions.
RESULTS
Deficits in infrastructure were in areas of patient care such as availability of oncology pharmacists, standard laboratories and diagnostic facilities, clinical equipment maintenance and regular calibrations, trained personnel for clinical trial activities, investigational products handling and disposals and lack of standard operating procedures for clinical activities. There were two GCP trained personnel, two study coordinators and one research pharmacist across the four sites. Interventions were instituted to address the observed deficits in all four sites which are now well positioned to undertake clinical trials in oncology. Training on all aspects of clinical trial was also provided.
CONCLUSIONS
Partnerships with institutions in HICs can successfully identify, address, and improve deficits in infrastructure for clinical trial in LMICs. The HICs should lead in providing funds, mentorship, and training for LMIC institutions to improve and expand clinical trials in LMIC countries.
Topics: Capacity Building; Clinical Trials as Topic; Humans; Models, Organizational; Neoplasms; Nigeria
PubMed: 32746811
DOI: 10.1186/s12913-020-05561-3 -
European Journal of Cancer (Oxford,... Sep 2020The use of overall survival (OS) as the gold standard primary end-point (PEP) in metastatic oncologic randomised controlled trials (RCTs) has declined in favour of... (Review)
Review
BACKGROUND
The use of overall survival (OS) as the gold standard primary end-point (PEP) in metastatic oncologic randomised controlled trials (RCTs) has declined in favour of progression-free survival (PFS) without a complete understanding of the degree to which PFS reliably predicts for OS.
METHODS
Using ClinicalTrials.gov, we identified 1239 phase III oncologic RCTs, 260 of which were metastatic solid tumour trials with a superiority-design investigating a therapeutic intervention by using either a PFS or OS PEP. Each individual trial was reviewed to quantify RCT design factors and disease-related outcomes.
RESULTS
A total of 172,133 patients were enrolled from the year 1999 to 2015 in RCTs that used PFS (56.2%, 146/260) or OS (43.8%, 114/260) as the PEP. PFS trials were more likely to restrict patient eligibility by using molecular criteria (15.1% versus 4.4%, p = 0.005) use targeted therapy (80.1% versus 67.5%, p = 0.048), accrue fewer patients (median 495 versus 619, p = 0.03), and successfully meet the trial PEP (66.9% versus 33.3%, p < 0.0001). On multiple binary logistic regression analysis, factors that predicted for PFS or OS PEP trial success included choice of PFS PEP (p < 0.0001), molecular profile restriction (p = 0.02) and single agent therapy (p = 0.02). Notably, there was only a 38% (31/82) conversion rate of positive PFS-to-OS benefit; lack of industry sponsorship predicted for PFS-to-OS signal conversion (80.0% without industry sponsorship versus 35.1% with industry sponsorship, p = 0.045).
CONCLUSIONS
A PFS PEP has suboptimal positive predictive value for OS among phase III metastatic solid tumour RCTs. Regulatory agency decisions should be judicious in using PFS results as the primary basis for approval.
Topics: Biomarkers; Clinical Trials, Phase III as Topic; Comparative Effectiveness Research; Equivalence Trials as Topic; Humans; Neoplasm Metastasis; Neoplasms; Predictive Value of Tests; Prognosis; Progression-Free Survival; Randomized Controlled Trials as Topic; Research Design; Survival Analysis; Treatment Outcome
PubMed: 32702645
DOI: 10.1016/j.ejca.2020.06.015 -
BMJ Open Jul 2022Malaria is one of the major public health problems in sub-Saharan Africa. It contributes significantly to maternal and fetal morbidity and mortality in affected...
INTRODUCTION
Malaria is one of the major public health problems in sub-Saharan Africa. It contributes significantly to maternal and fetal morbidity and mortality in affected countries. This study aims to evaluate the impact of enhanced case detection using molecular testing called loop-mediated isothermal amplification (LAMP) on birth outcomes in a prospective study design.
METHODS AND ANALYSIS
A pragmatic randomised diagnostic outcomes trial will be conducted in several health institutes in different Ethiopian regions. Women (n=2583) in their first and second trimesters of pregnancy will be included in the study and individually randomised to the standard of care or enhanced case detection arms, and followed until delivery. Enrolment will encompass the malaria peak transmission seasons. In the standard of care arm, a venous blood sample will be collected for malaria diagnosis only in symptomatic patients. In contrast, in the intervention arm, mothers will be tested by a commercially available Conformité Européene (CE)-approved LAMP malaria test, microscopy and rapid diagnostic test for malaria regardless of their symptoms at each antenatal care visit. The primary outcome of the study is to measure birth weight.
ETHICS AND DISSEMINATION
The study was approved by the following ethical research boards: Armauer Hansen Research Institute/ALERT Ethics Review Committee (FORM AF-10-015.1, Protocol number PO/05/20), the Ethiopia Ministry of Science and Higher Education National Research Ethics Review Committee (approval SRA/11.7/7115/20), the Ethiopia Food and Drug Administration (approval 02/25/33/I), UCalgary Conjoint Health Research Ethics Board (REB21-0234). The study results will be shared with the institutions and stakeholders such as the Ethiopia Ministry of Health, the Foundation for Innovative Diagnostics, WHO's Multilateral initiative on Malaria - Tropical Diseases Research (TDR-MIM), Roll Back Malaria and the Malaria in Pregnancy Consortium. The study results will also be published in peer-reviewed journals and presented at international conferences.
TRIAL REGISTRATION NUMBER
NCT03754322.
Topics: Female; Humans; Malaria; Mass Screening; Molecular Diagnostic Techniques; Nucleic Acid Amplification Techniques; Pragmatic Clinical Trials as Topic; Pregnancy; Pregnancy Complications, Parasitic; Prospective Studies; Randomized Controlled Trials as Topic; Technology
PubMed: 35851027
DOI: 10.1136/bmjopen-2021-058397 -
Journal of the National Cancer Institute Dec 2019Two decades following the creation of the Office of Cancer Complementary and Alternative Medicine at the National Cancer Institute, the status of complementary and... (Review)
Review
Two decades following the creation of the Office of Cancer Complementary and Alternative Medicine at the National Cancer Institute, the status of complementary and alternative medicine (CAM) research within oncology remains opaque. To better understand the landscape of CAM studies in oncology, we identified CAM-related phase III randomized controlled trials (RCTs) through ClinicalTrials.gov and compared these CAM trials to all non-CAM oncologic RCTs. Pearson χ2 testing was used to compare proportions across groups; all tests were two-sided. Comparing the 25 identified CAM RCTs with 739 non-CAM RCTs, CAM studies were more likely to be sponsored by a cooperative group (64.0% vs 28.6%, P < .001) and less likely to be industry funded (8.0% vs 76.5%, P < .001). CAM trials disproportionately excluded disease-related outcomes as endpoints (8.0% vs 84.6%, P < .001), were unsupported by prior early-phase data (55.0% vs 96.1%, P < .001), and did not meet the primary endpoint (8.7% vs 53.0%, P < .001). Given the observed relationship between encouraging pilot data and subsequent phase III trial success, we contend that future CAM RCTs may yield more promising findings if better supported by appropriately designed and well-characterized early-phase signals.
Topics: Chi-Square Distribution; Clinical Trials, Phase III as Topic; Complementary Therapies; Humans; Medical Oncology; National Cancer Institute (U.S.); Neoplasms; Progression-Free Survival; Randomized Controlled Trials as Topic; Research Support as Topic; Treatment Outcome; United States
PubMed: 31165160
DOI: 10.1093/jnci/djz117 -
Fertility and Sterility Nov 2021To characterize the interventional clinical trials in infertility and to assess whether trial location or industry sponsorship was associated with trial noncompletion.
OBJECTIVE
To characterize the interventional clinical trials in infertility and to assess whether trial location or industry sponsorship was associated with trial noncompletion.
DESIGN
Retrospective review of trials registered with ClinicalTrials.gov.
SETTING
None.
PATIENT(S)
None.
INTERVENTION(S)
None.
MAIN OUTCOME MEASURE(S)
Descriptive statistics characterizing the attributes of the clinical trials including intervention type, topic, population, completion status, size, location, sponsor, and results. The effects of the sponsor and trial location on trial noncompletion were assessed via logistic regression.
RESULT(S)
In total, 505 trials initiated between 2010 and 2020 were included in our analysis. Drug interventions were the most commonly studied (45%); ovarian stimulation trials accounted for 27% of the studies. Live birth was tracked as an outcome by 20% of the studies; 3% of the trials included mental health outcomes. Few trials (15%) enrolled male participants. Only 11% of the trials reported results, and 4% of the trials reported the race or ethnicity of the participants. Most trials (82%) were conducted outside the United States. Overall, 18% of the trials were not completed, most often because of lack of accrual (47%). United States trials had over twice the odds of noncompletion in univariate analysis (odds ratio = 2.48, 95% confidence interval = [1.47, 4.17]); however, this relationship lost significance after adjusting for potential confounders (odds ratio = 0.95, 95% confidence interval = [0.42, 2.14]). Trial sponsorship was not associated with trial noncompletion.
CONCLUSION(S)
Infertility trials predominantly investigated drug interventions, particularly ovarian stimulation. Live birth was an infrequent outcome despite its relevance to patients. Clinical trials should aim to address the unmet needs in fertility care and be inclusive of underserved populations affected by infertility.
Topics: Clinical Trials as Topic; Databases, Factual; Diffusion of Innovation; Endpoint Determination; Female; Fertility; Health Care Sector; Humans; Infertility; Live Birth; Male; Multicenter Studies as Topic; Pregnancy; Pregnancy Rate; Reproductive Medicine; Reproductive Techniques, Assisted; Research Design; Research Support as Topic; Retrospective Studies; Treatment Outcome
PubMed: 34256949
DOI: 10.1016/j.fertnstert.2021.06.013 -
Gut Feb 2021Central reading, that is, independent, off-site, blinded review or reading of imaging endpoints, has been identified as a crucial component in the conduct and analysis... (Review)
Review
Central reading, that is, independent, off-site, blinded review or reading of imaging endpoints, has been identified as a crucial component in the conduct and analysis of inflammatory bowel disease clinical trials. Central reading is the final step in a workflow that has many parts, all of which can be improved. Furthermore, the best reading algorithm and the most intensive central reader training cannot make up for deficiencies in the acquisition stage (clinical trial endoscopy) or improve on the limitations of the underlying score (outcome instrument). In this review, academic and industry experts review scoring systems, and propose a theoretical framework for central reading that predicts when improvements in statistical power, affecting trial size and chances of success, can be expected: Multireader models can be conceptualised as statistical or non-statistical (social). Important organisational and operational factors, such as training and retraining of readers, optimal bowel preparation for colonoscopy, video quality, optimal or at least acceptable read duration times and other quality control matters, are addressed as well. The theory and practice of central reading and the conduct of endoscopy in clinical trials are interdisciplinary topics that should be of interest to many, regulators, clinical trial experts, gastroenterology societies and those in the academic community who endeavour to develop new scoring systems using traditional and machine learning approaches.
Topics: Algorithms; Clinical Trials as Topic; Colonoscopy; Endpoint Determination; Forecasting; Humans; Inflammatory Bowel Diseases; Observer Variation
PubMed: 32699100
DOI: 10.1136/gutjnl-2020-320690 -
Medicina Clinica Jan 2021
Topics: Bibliometrics; Biomedical Research; COVID-19; Clinical Trials as Topic; Global Health; Humans; Pandemics; Publishing; Spain
PubMed: 33268132
DOI: 10.1016/j.medcli.2020.09.001 -
Cell Apr 2020Integrating precision diagnostics into personalized treatments requires understanding how biomarkers relate to clinical outcomes. Various clinical data collection...
Integrating precision diagnostics into personalized treatments requires understanding how biomarkers relate to clinical outcomes. Various clinical data collection methods exist, each with strengths and weaknesses. Interventional data are high quality but narrowly focused. Real-world data (RWD) provide broader information but with variable quality. Master protocols allow better efficiency in data collection. The master observational trial bridges the gap between interventional and retrospective RWD collection methods. To view this SnapShot, open or download the PDF.
Topics: Clinical Trials as Topic; Data Collection; Humans; Precision Medicine
PubMed: 32243791
DOI: 10.1016/j.cell.2020.02.032 -
PloS One 2022To assess the accuracy of principal investigators' (PIs) predictions about three events for their own clinical trials: positivity on trial primary outcomes, successful...
OBJECTIVE
To assess the accuracy of principal investigators' (PIs) predictions about three events for their own clinical trials: positivity on trial primary outcomes, successful recruitment and timely trial completion.
STUDY DESIGN AND SETTING
A short, electronic survey was used to elicit subjective probabilities within seven months of trial registration. When trial results became available, prediction skill was calculated using Brier scores (BS) and compared against uninformative prediction (i.e. predicting 50% all of the time).
RESULTS
740 PIs returned surveys (16.7% response rate). Predictions on all three events tended to exceed observed event frequency. Averaged PI skill did not surpass uninformative predictions (e.g., BS = 0.25) for primary outcomes (BS = 0.25, 95% CI 0.20, 0.30) and were significantly worse for recruitment and timeline predictions (BS 0.38, 95% CI 0.33, 0.42; BS = 0.52, 95% CI 0.50, 0.55, respectively). PIs showed poor calibration for primary outcome, recruitment, and timelines (calibration index = 0.064, 0.150 and 0.406, respectively), modest discrimination in primary outcome predictions (AUC = 0.76, 95% CI 0.65, 0.85) but minimal discrimination in the other two outcomes (AUC = 0.64, 95% CI 0.57, 0.70; and 0.55, 95% CI 0.47, 0.62, respectively).
CONCLUSION
PIs showed overconfidence in favorable outcomes and exhibited limited skill in predicting scientific or operational outcomes for their own trials. They nevertheless showed modest ability to discriminate between positive and non-positive trial outcomes. Low survey response rates may limit generalizability.
Topics: Clinical Trials as Topic; Forecasting; Research Personnel; Surveys and Questionnaires; Treatment Outcome
PubMed: 35134071
DOI: 10.1371/journal.pone.0262862 -
Journal of the American College of... Oct 2019Most major clinical trials in cardiology report time-to-event outcomes using the Cox proportional hazards model so that a treatment effect is estimated as the hazard... (Review)
Review
Most major clinical trials in cardiology report time-to-event outcomes using the Cox proportional hazards model so that a treatment effect is estimated as the hazard ratio between groups, accompanied by its 95% confidence interval and a log-rank p value. But nonproportionality of hazards (non-PH) over time occurs quite often, making alternative analysis strategies appropriate. This review presents real examples of cardiology trials with different types of non-PH: an early treatment effect, a late treatment effect, and a diminishing treatment effect. In such scenarios, the relative merits of a Cox model, an accelerated failure time model, a milestone analysis, and restricted mean survival time are examined. Some post hoc analyses for exploring any specific pattern of non-PH are also presented. Recommendations are made, particularly regarding how to handle non-PH in pre-defined Statistical Analysis Plans, trial publications, and regulatory submissions.
Topics: Cardiology; Clinical Trials as Topic; Coronary Artery Bypass; Heart Diseases; Humans; Kaplan-Meier Estimate; Proportional Hazards Models; Randomized Controlled Trials as Topic; Research Design; Statistics as Topic; Survival Analysis; Survival Rate; Time Factors; Treatment Outcome
PubMed: 31623769
DOI: 10.1016/j.jacc.2019.08.1034