Trends in PRO reporting in clinical trials leading to GU cancer drug approvals from 2007 to 2018.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 641-641
Author(s):  
Monica Tamil ◽  
Houssein Safa ◽  
Adele Semaan ◽  
Jad Chahoud
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Standards Of Care ◽  
Cancer Drug ◽  
Type I ◽  
Cancer Drugs ◽  
Urological Cancer ◽  
Quality Reporting ◽  
Patient Reported ◽  
Drug Approvals

641 Background: Having standardized and high quality reporting of patient reported outcomes (PRO), especially in clinical trials that establish standards of care in oncology is important for patient centered care. This study assessed the status of reporting and quality of analysis of PROs in FDA approved drugs for genitourinary malignancies. Methods: We conducted a systematic review of the FDA archives to identify urological cancer drugs approved between 2007-2018. We retrieved the clinical trials that led to these drug approvals from ClinicalTrials.gov and PubMed. We systematically screened for PROs and reviewed their analytic tools and interpretation methods reported in their published manuscripts and study protocols. A clinical trial was considered to include PROs if they were reported in either the primary or a subsequent manuscript. Results: We identified 22 clinical trials leading to FDA approval of urological cancer drugs between 2007-2018. Only 63% of trials had published PROs. PROs were reported in the primary clinical trial manuscripts for two drugs (9%), and in a secondary PRO manuscript for 12 drugs (54%). The median time between the primary and secondary papers was 12 months (IQR:7.5-26 months). Among the 14 published PRO papers, the hypothesis was broad in 79%, and not reported in 21%. PROs were never included as a primary endpoint of a study. Instead, PROs were reported as secondary endpoints in 5 (36%) and as exploratory endpoints in 7 (50%) studies, while two papers (14%) did not mention PRO reporting in their endpoints. The most common PRO instruments were EQ-5D (64%) and FACT-P (50%). In 92% of PRO papers, statistical analyses were conducted to account for missing data. Control for type I error was needed but not done in 57% of the trials. Conclusions: Delays in publication of PROs occur regularly in trials leading to drug approval in GU malignancies. Our study highlights the need to enhance standardization of the analysis and interpretation of PROs to maximize the value of this data for drug development and approval.

Trends in PRO reporting in clinical trials leading to cancer immunotherapy drug approvals from 2011 to 2019.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 105-105
Author(s):  
Houssein Safa ◽  
Monica Tamil ◽  
Adi Diab ◽  
Adele Semaan ◽  
Jad Chahoud
Keyword(s):  
Clinical Trials ◽  
Cancer Immunotherapy ◽  
Current Trend ◽  
Type I ◽  
Patient Centeredness ◽  
Quality Reporting ◽  
Study Protocols ◽  
Fda Approval ◽  
Patient Reported ◽  
Drug Approvals

105 Background: Patient-reported outcomes (PROs) are a primary tool to evaluate the effect of a given drug on the health-related quality of life from a patient’s perspective and to maximize the value of patient-centeredness in drug development and approval. In this study, we aimed to evaluate the current trend in reporting, analysis and interpretation of PRO data. Methods: We conducted a systematic review of the FDA archives, identifying all cancer immunotherapy drug approvals between the years 2011 and 2019. We then retrieved the clinical trials that respectively led to these drug approvals from PubMed and ClinicalTrials.gov. We systematically screened for PROs and assessed their analytic tools and interpretation methods that were collected from the published journal articles and their study protocols. If one FDA approval was supported by more than one clinical trial, we included all studies in our review. An FDA approval was considered to include PROs if they were reported in at least one of the supporting trials. Results: Thirty-seven clinical trials leading to 35 immunotherapy drug approvals were identified. More than half (54%) did not publish any PROs. While PROs were reported in the primary clinical outcomes manuscript of 4 trials (11%) and in a secondary separately published paper for 13 trials (35%). The median time between the primary and secondary papers was 22 months (range: 5 - 40). In the 17 published PROs, the hypothesis was broad in 12 (71%), not reported in 4 (24%) and specific in only 1 (6%). Ten (59%) were reported as exploratory endpoints, five (29%) as secondary endpoints, and two (12%) did not specify the PRO reporting in their endpoints. The most common PRO instruments were EQ-5D (71%) and QLQ-C30 (65%). Control for type I error was needed but not done in 15 (88%). Fourteen (82%) described an approach for dealing with missing PRO assessments. None reported on significant differences based on race and ethnicity of participants. Conclusions: Suboptimal reporting and delays in publication of PROs occur regularly in cancer immunotherapy trials. Increased efforts are needed to enhance standardization and quality reporting of PROs to maximize the value of this data in cancer immunotherapy drug approval.

Timing of US Food and Drug Administration (FDA) cancer drug approvals relative to publication of clinical trial results.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2071-2071 ◽  
Author(s):  
Ali Raza Khaki ◽  
Aakash Desai ◽  
Martin W. Schoen ◽  
Bishal Gyawali ◽  
Eddy J. Chen ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Cancer Treatments ◽  
Fda Approval ◽  
Anti Cancer ◽  
Accelerated Approval ◽  
Drug Approvals ◽  
Clinical Trial Results ◽  
Careful Assessment

2071 Background: Publication of clinical trial results in peer reviewed literature is essential to inform clinicians regarding the use of new anti-cancer treatments, which often have a low therapeutic ratio and require careful assessment of risks and benefits. Publication of registration trials should precede FDA approval to facilitate evaluation and implementation of new therapies. The timing of trial publication relative to FDA drug approvals has not been systematically investigated. Methods: We collected all FDA drug approvals for a cancer indication between 2000-19. Trials were identified using FDA labels as well as drugs and publications indexed on HemOnc.org. Approvals for generics/biosimilars, non-oncology indications and label revisions without supportive evidence were excluded. Dates of approval, the approval pathway, approval type (new vs expansion), and the first full publication related to the registration were recorded. Trials and approvals were matched using available metadata. We calculated the proportion of drugs approved prior to publication overall and for those receiving accelerated approval (AA). We used logistic regression to compare rates of pre-publication approval by approval pathway and by new vs expanded approval. Results: Among a total of 378 drug approvals, 139 (37%) had pre-publication approval. Of these, the median overall time from approval to publication was 140 days (IQR 64-281 days). For those with approval after publication, median time from publication to approval was 157 days (IQR 72-359 days). The number of drugs approved pre-publication rose by 27% between the first and last quarters of the study period, though, the proportion decreased as more anti-cancer drugs have been approved in recent years (Table). More drugs were approved pre-publication through AA than regular approval (46% vs 34%, OR 1.66 [95% CI 1.03-2.70], p=0.04) and as new approvals vs. expanded approvals (45% vs 32%, OR 1.76 [95% CI 1.15-2.70], p=0.01). Conclusions: A substantial minority of FDA approvals occur before trial results are published, with the odds being higher for drugs receiving AA and for new approvals. Since clinicians rely upon published results to inform risk/benefit decisions, efforts are needed to ensure trial results are published by the time of FDA approval of new cancer drugs and indications. [Table: see text]

scholarly journals Landmark Cancer Clinical Trials and Real-World Patient Populations: Examining Race and Age Reporting

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5770
Author(s):  
Thejus Jayakrishnan ◽  
Sonikpreet Aulakh ◽  
Mizba Baksh ◽  
Kianna Nguyen ◽  
Meghna Ailawadhi ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Real World ◽  
Age Distribution ◽  
Mean Difference ◽  
Cancer Drug ◽  
P Value ◽  
World Population ◽  
Drug Approvals ◽  
Age Disparity

Background: Concern exists that the clinical trial populations differ from respective cancer populations in terms of their age distribution affecting the generalizability of the results, especially in underrepresented minorities. We hypothesized that the clinical trials that do not report race are likely to suffer from a higher degree of age disparity. Methods: Food and Drug Administration (FDA) drug approvals from July 2007 to June 2019 were reviewed to identify oncology approvals, and trials with age details were selected. The outcomes studied were the weighted mean difference in age between the clinical trial population and real-world population for various cancers, the prevalence of race reporting and association of age and race reporting with each other. Results: Of the 261 trials, race was reported in 223 (85.4%) of the trials, while 38 trials (14.6%) had no mention of race. Race reporting improved minimally over time: 29 (85.3%) in 2007–2010 vs. 49 (80.3%) in 2011–2014 vs. 145 (85.4%) during the period 2015–2019 (p-value = 0.41). Age discrepancy between the clinical trial population and the real-world population was higher for studies that did not report race (mean difference −8.8 years (95% CI −12.6 to −5.0 years)) vs. studies that did report it (mean difference −5.1 years, (95% CI −6.4 to −3.7 years), p-value = 0.04). Conclusion: The study demonstrates that a significant number of clinical trials leading to cancer drug approvals suffer from racial and age disparity when compared to real-world populations, and that the two factors may be interrelated. We recommend continued efforts to recruit diverse populations.

Core limitations in clinical trials leading to anticancer drug approvals by the U.S. Food and Drug Administration.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2057-2057
Author(s):  
Talal Hilal ◽  
Miguel Gonzalez-Velez ◽  
Vinay Prasad
Keyword(s):  
Clinical Trial ◽  
Optimal Control ◽  
Overall Survival ◽  
Clinical Trials ◽  
Drug Administration ◽  
Randomized Trials ◽  
Food And Drug Administration ◽  
Cancer Drug ◽  
Anti Cancer ◽  
Drug Approvals

2057 Background: To date, a comprehensive evaluation of core limitations in clinical trials leading to anti-cancer drug approvals by the US Food and Drug Administration (FDA) has not been undertaken.The aim of this analysis was to assess the percentage of clinical trials with core limitations, defined as lack of randomization, lack of overall survival data, inappropriate use of crossover, and use of sub-optimal control arms that led to FDA approvals from 2014 to 2019. Methods: This observational analysis included all approved anti-cancer drug indications by the FDA from July 2014 through July 2019. All indications were investigated and each clinical trial evaluated for design, enrollment period, primary endpoints, and presence of core limitations. The standard of care therapy was determined by evaluating the literature and published guidelines 1-year prior to start of clinical trial enrollment. Crossover was examined and evaluated for optimal use. We then calculated the percentage of approvals based on clinical trials with any or all core limitations. Results: A total of 187 anti-cancer approvals were evaluated. The number of anti-cancer drug approvals doubled over time with 68 in first half of study period (June 2014 to December 2016) to 119 in second half of study period (January 2017 to July 2019). Of those, 125 (67%) were based on a clinical trial with at least one core limitation. 64 (34%) approvals were based on a single-arm clinical trial. Of the remaining 123 approvals based on randomized trials, 60 (32%) had a core limitation. Of all randomized trials, 37 (30%) lacked overall survival benefit, 31 (25%) had a sub-optimal control, and 17 (14%) used crossover inappropriately. Conclusions: The majority of cancer drugs are approved based on clinical trials with core limitations. Efforts to minimize core limitations at the time of clinical trial design are essential to ensure that new anti-cancer drugs being marketed truly improve patient outcomes over current standards.

scholarly journals Longitudinal Analysis of Patient-Reported Outcomes in Clinical Trials: Applications of Multilevel and Multidimensional Item Response Theory

Psychometrika ◽  
2021 ◽  
Author(s):  
Li Cai ◽  
Carrie R. Houts
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Latent Variable ◽  
Patient Reported Outcomes ◽  
Multilevel Models ◽  
Latent Variable Models ◽  
Trial Data ◽  
Regulatory Science ◽  
Measurement Information ◽  
Patient Reported

AbstractWith decades of advance research and recent developments in the drug and medical device regulatory approval process, patient-reported outcomes (PROs) are becoming increasingly important in clinical trials. While clinical trial analyses typically treat scores from PROs as observed variables, the potential to use latent variable models when analyzing patient responses in clinical trial data presents novel opportunities for both psychometrics and regulatory science. An accessible overview of analyses commonly used to analyze longitudinal trial data and statistical models familiar in both psychometrics and biometrics, such as growth models, multilevel models, and latent variable models, is provided to call attention to connections and common themes among these models that have found use across many research areas. Additionally, examples using empirical data from a randomized clinical trial provide concrete demonstrations of the implementation of these models. The increasing availability of high-quality, psychometrically rigorous assessment instruments in clinical trials, of which the Patient-Reported Outcomes Measurement Information System (PROMIS®) is a prominent example, provides rare possibilities for psychometrics to help improve the statistical tools used in regulatory science.

Clinical Trial Design and Statistics

2018 ◽  
Author(s):  
Julie Ann Sosa
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Data Analysis ◽  
Trial Design ◽  
New Technologies ◽  
Drug Application ◽  
Clinical Trial Design ◽  
Double Blind Study ◽  
Type I ◽  
End Points

A clinical trial is a planned experiment designed to prospectively measure the efficacy or effectiveness of an intervention by comparing outcomes in a group of subjects treated with the test intervention with those observed in one or more comparable group(s) of subjects receiving another intervention.  Historically, the gold standard for a clinical trial has been a prospective, randomized, double-blind study, but it is sometimes impractical or unethical to conduct such in clinical medicine and surgery. Conventional outcomes have traditionally been clinical end points; with the rise of new technologies, however, they are increasingly being supplemented and/or replaced by surrogate end points, such as serum biomarkers. Because patients are involved, safety considerations and ethical principles must be incorporated into all phases of clinical trial design, conduct, data analysis, and presentation. This review covers the history of clinical trials, clinical trial phases, ethical issues, implementing the study, basic biostatistics for data analysis, and other resources. Figures show drug development and clinical trial process, and type I and II error. Tables list Food and Drug Administration new drug application types, and types of missing data in clinical trials. This review contains 2 highly rendered figures, 2 tables, and 38 references

scholarly journals End points for sickle cell disease clinical trials: patient-reported outcomes, pain, and the brain

2019 ◽  
Vol 3 (23) ◽  
pp. 3982-4001 ◽  
Author(s):  
Ann T. Farrell ◽  
Julie Panepinto ◽  
C. Patrick Carroll ◽  
Deepika S. Darbari ◽  
Ankit A. Desai ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Patient Reported Outcomes ◽  
Cell Disease ◽  
End Points ◽  
Additional Clinical Trial ◽  
Patient Reported ◽  
The Brain

Abstract To address the global burden of sickle cell disease (SCD) and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to: patient-reported outcomes (PROs), pain (non-PROs), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the PROs, pain, and brain panels, as well as relevant findings and recommendations from the biomarkers panel. The panels identify end points, where there were supporting data, to use in clinical trials of SCD. In addition, the panels discuss where further research is needed to support the development and validation of additional clinical trial end points.

scholarly journals Disparity of Race Reporting and Representation in Clinical Trials Leading to Cancer Drug Approvals From 2008 to 2018

JAMA Oncology ◽  
2019 ◽  
Vol 5 (10) ◽  
pp. e191870 ◽  
Author(s):  
Jonathan M. Loree ◽  
Seerat Anand ◽  
Arvind Dasari ◽  
Joseph M. Unger ◽  
Anirudh Gothwal ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cancer Drug ◽  
Drug Approvals

scholarly journals The impact of patient-reported outcome (PRO) data from clinical trials: a systematic review and critical analysis

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Samantha Cruz Rivera ◽  
Derek G. Kyte ◽  
Olalekan Lee Aiyegbusi ◽  
Anita L. Slade ◽  
Christel McMullan ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Case Studies ◽  
Real World ◽  
Clinical Trial Data ◽  
Research Impact ◽  
Trial Data ◽  
Patient Reported ◽  
The Impact

Abstract Background Patient-reported outcomes (PROs) are commonly collected in clinical trials and should provide impactful evidence on the effect of interventions on patient symptoms and quality of life. However, it is unclear how PRO impact is currently realised in practice. In addition, the different types of impact associated with PRO trial results, their barriers and facilitators, and appropriate impact metrics are not well defined. Therefore, our objectives were: i) to determine the range of potential impacts from PRO clinical trial data, ii) identify potential PRO impact metrics and iii) identify barriers/facilitators to maximising PRO impact; and iv) to examine real-world evidence of PRO trial data impact based on Research Excellence Framework (REF) impact case studies. Methods Two independent investigators searched MEDLINE, EMBASE, CINAHL+, HMIC databases from inception until December 2018. Articles were eligible if they discussed research impact in the context of PRO clinical trial data. In addition, the REF 2014 database was systematically searched. REF impact case studies were included if they incorporated PRO data in a clinical trial. Results Thirty-nine publications of eleven thousand four hundred eighty screened met the inclusion criteria. Nine types of PRO trial impact were identified; the most frequent of which centred around PRO data informing clinical decision-making. The included publications identified several barriers and facilitators around PRO trial design, conduct, analysis and report that can hinder or promote the impact of PRO trial data. Sixty-nine out of two hundred nine screened REF 2014 case studies were included. 12 (17%) REF case studies led to demonstrable impact including changes to international guidelines; national guidelines; influencing cost-effectiveness analysis; and influencing drug approvals. Conclusions PRO trial data may potentially lead to a range of benefits for patients and society, which can be measured through appropriate impact metrics. However, in practice there is relatively limited evidence demonstrating directly attributable and indirect real world PRO-related research impact. In part, this is due to the wider challenges of measuring the impact of research and PRO-specific issues around design, conduct, analysis and reporting. Adherence to guidelines and multi-stakeholder collaboration is essential to maximise the use of PRO trial data, facilitate impact and minimise research waste. Trial registration Systematic Review registration PROSPERO CRD42017067799.

Developing symptom management quality improvement reports with data from a registry-based patient reported outcomes (PRO) collection method.

2014 ◽  
Vol 32 (30_suppl) ◽  
pp. 180-180
Author(s):  
Tenbroeck Smith ◽  
Kathleen Castro ◽  
Alyssa Troeschel ◽  
Neeraj K. Arora ◽  
Kevin Stein ◽  
...  
Keyword(s):  
Quality Improvement ◽  
Health Professional ◽  
Symptom Management ◽  
Patient Reported Outcomes ◽  
Standards Of Care ◽  
Cancer Type ◽  
Cancer Centers ◽  
Quality Reporting ◽  
Management Quality ◽  
Patient Reported

180 Background: Symptom management is critical to quality cancer care, affecting treatment completion, functioning and quality of life. We describe the use of the Commission on Cancer’s Rapid Quality Reporting System (RQRS) to ascertain cases for PRO collection, identify key PRO quality indicators, and provide actionable symptom management quality improvement (QI) reports to community cancer centers (CCC). Methods: The Patient Reported Outcomes Symptoms & Side Effects Study used RQRS to sample patients (pt) 4-12 months from diagnosis with locoregional breast/colon from 17 National Cancer Institute Community Cancer Centers Program centers. Surveys were mailed with web option. Pts were asked if they talked to a health professional about pain (Talk about) and, separately, if the health professional gave advice about what to do if pain started, got worse, or came back (Advice). Similar questions were asked about fatigue and emotional distress (ED). QI reports were designed with CCC staff feedback and produced for each CCC providing crude and case-mix adjusted CCC-specific rates, and study-wide rates. Direct standardization methods were used to adjust CCC-specific rates for cancer type and education. Results: 2,487 eligible participants responded (RR=61%). This table shows overall study-wide estimates and the range of adjusted CCC-specific estimates for six key indicators. (See Table.) Conclusions: This pilot study shows the registry-based method for PRO collection was successful and has potential for wider dissemination. Study-wide, 20-45% of pts did not report discussing or getting advice about three common symptoms from their healthcare team. CCCs varied significantly on these indicators, suggesting room for improvement. Quality reports were well received by hospital staff, who report sharing them with clinicians, navigators and cancer committees. CCC-specific reports may promote efforts to improve care through professional/patient education and applying standards of care. [Table: see text]

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