scholarly journals Bayesian clinical trials at The University of Texas MD Anderson Cancer Center: An update

2019 ◽  
Vol 16 (6) ◽  
pp. 645-656 ◽  
Author(s):  
Rebecca S Slack Tidwell ◽  
S Andrew Peng ◽  
Minxing Chen ◽  
Diane D Liu ◽  
Ying Yuan ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Personalized Medicine ◽  
Bayesian Methods ◽  
Trial Design ◽  
Large Scale ◽  
Dose Finding ◽  
Phase Iii ◽  
Ethical Review ◽  
Cancer Center ◽  
Md Anderson

Background/aims In our 2009 article, we showed that Bayesian methods had established a foothold in developing therapies in our institutional oncology trials. In this article, we will document what has happened since that time. In addition, we will describe barriers to implementing Bayesian clinical trials, as well as our experience overcoming them. Methods We reviewed MD Anderson Cancer Center clinical trials submitted to the institutional protocol office for scientific and ethical review between January 2009 and December 2013, the same length time period as the previous article. We tabulated Bayesian methods implemented for design or analyses for each trial and then compared these to our previous findings. Results Overall, we identified 1020 trials and found that 283 (28%) had Bayesian components so we designated them as Bayesian trials. Among MD Anderson–only and multicenter trials, 56% and 14%, respectively, were Bayesian, higher rates than our previous study. Bayesian trials were more common in phase I/II trials (34%) than in phase III/IV (6%) trials. Among Bayesian trials, the most commonly used features were for toxicity monitoring (65%), efficacy monitoring (36%), and dose finding (22%). The majority (86%) of Bayesian trials used non-informative priors. A total of 75 (27%) trials applied Bayesian methods for trial design and primary endpoint analysis. Among this latter group, the most commonly used methods were the Bayesian logistic regression model (N = 22), the continual reassessment method (N = 20), and adaptive randomization (N = 16). Median institutional review board approval time from protocol submission was the same 1.4 months for Bayesian and non-Bayesian trials. Since the previous publication, the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial was the first large-scale decision trial combining multiple treatments in a single trial. Since then, two regimens in breast cancer therapy have been identified and published from the cooperative Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis (I-SPY 2), enhancing cooperation among investigators and drug developers across the nation, as well as advancing information needed for personalized medicine. Many software programs and Shiny applications for Bayesian trial design and calculations are available from our website which has had more than 21,000 downloads worldwide since 2004. Conclusion Bayesian trials have the increased flexibility in trial design needed for personalized medicine, resulting in more cooperation among researchers working to fight against cancer. Some disadvantages of Bayesian trials remain, but new methods and software are available to improve their function and incorporation into cancer clinical research.

scholarly journals Personalized Medicine in a Phase I Clinical Trials Program: The MD Anderson Cancer Center Initiative

2012 ◽  
Vol 18 (22) ◽  
pp. 6373-6383 ◽  
Author(s):  
Apostolia-Maria Tsimberidou ◽  
Nancy G. Iskander ◽  
David S. Hong ◽  
Jennifer J. Wheler ◽  
Gerald S. Falchook ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Personalized Medicine ◽  
Phase I ◽  
Cancer Center ◽  
Phase I Clinical Trials ◽  
Md Anderson

scholarly journals Unconventional Anticancer Agents: A Systematic Review of Clinical Trials

2006 ◽  
Vol 24 (1) ◽  
pp. 136-140 ◽  
Author(s):  
Andrew J. Vickers ◽  
Joyce Kuo ◽  
Barrie R. Cassileth
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Cancer Patients ◽  
Phase Ii ◽  
Dose Finding ◽  
Phase Iii ◽  
High Dose ◽  
Free Text ◽  
Phase Ii Trials ◽  
Off Label

Purpose A substantial number of cancer patients turn to treatments other than those recommended by mainstream oncologists in an effort to sustain tumor remission or halt the spread of cancer. These unconventional approaches include botanicals, high-dose nutritional supplementation, off-label pharmaceuticals, and animal products. The objective of this study was to review systematically the methodologies applied in clinical trials of unconventional treatments specifically for cancer. Methods MEDLINE 1966 to 2005 was searched using approximately 200 different medical subject heading terms (eg, alternative medicine) and free text words (eg, laetrile). We sought prospective clinical trials of unconventional treatments in cancer patients, excluding studies with only symptom control or nonclinical (eg, immune) end points. Trial data were extracted by two reviewers using a standardized protocol. Results We identified 14,735 articles, of which 214, describing 198 different clinical trials, were included. Twenty trials were phase I, three were phase I and II, 70 were phase II, and 105 were phase III. Approximately half of the trials investigated fungal products, 20% investigated other botanicals, 10% investigated vitamins and supplements, and 10% investigated off-label pharmaceuticals. Only eight of the phase I trials were dose-finding trials, and a mere 20% of phase II trials reported a statistical design. Of the 27 different agents tested in phase III, only one agent had a prior dose-finding trial, and only for three agents was the definitive study initiated after the publication of phase II data. Conclusion Unconventional cancer treatments have not been subject to appropriate early-phase trial development. Future research on unconventional therapies should involve dose-finding and phase II studies to determine the suitability of definitive trials.

Designing a clinical trial for neurorehabilitation

2020 ◽  
pp. 47-60
Author(s):  
Bruce Dobkin ◽  
Clarisa Martinez
Keyword(s):  
Clinical Trials ◽  
Gold Standard ◽  
Trial Design ◽  
Large Scale ◽  
Randomized Clinical Trials ◽  
Neurological Diseases ◽  
Parallel Group ◽  
Study Participants ◽  
Parallel Group Trial ◽  
Group Trial

The design, implementation, and analysis of clinical trials for the types of complex therapies needed to lessen impairments and disabilities that result from neurological diseases are reviewed. A multistep progression from feasibility testing in small groups of selected participants to the demonstration of efficacy in large-scale, multicentre randomized clinical trials is presented. Designs other than the ‘gold standard’ parallel-group trial can be used to optimize the contents of a new therapeutic strategy. Emphasis is placed on defining clinical characteristics and establishing a stable functional baseline for study participants. How the choices of outcome measure and comparison intervention affect the statistical and clinical significance of trial results are highlighted. Discussion of methodological concerns about randomization and blinded outcome assessment is followed by a review of common statistical confounders in neurorehabilitation trials. The use of consensus standards about trial reporting provides a valuable checklist for basic decisions in trial design.

Trial design from a clinical perspective

ESC CardioMed ◽  
2018 ◽  
pp. 3067-3071
Author(s):  
John G. F. Cleland ◽  
Ian Ford
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Trial Design ◽  
Statistical Significance ◽  
Well Being ◽  
Phase Iii ◽  
Practical Significance ◽  
Commercial Company ◽  
Phase Iii Trials ◽  
General Guidance

This chapter is written primarily from the perspective of investigators with limited resources designing clinical trials to assess the effects of interventions on patient well-being and outcomes with the hope that the results might influence clinical practice and guidelines. Other perspectives should be taken into account. The advice may be less applicable when resources are abundant (e.g. phase III trials sponsored by a large commercial company). Much research is funded by commercial companies hoping for a return on investment; they will design clinical trials to increase the chance of a statistically positive result. Many investigators will do the same although their motivation may differ. However, practising clinicians, patients, and health services want trials that help inform their daily clinical practice rather than merely achieving statistical significance. Large studies may be statistically positive but of dubious practical significance. This chapter gives some general guidance on selecting patients, comparators, endpoints, and study design.

Safety and Evidence of Off-Label Use of Approved Drugs at the National Cancer Center Hospital in Japan

2020 ◽  
pp. OP.20.00131
Author(s):  
Seiko Bun ◽  
Kan Yonemori ◽  
Hiroko Sunadoi ◽  
Rena Nishigaki ◽  
Emi Noguchi ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Pharmaceutical Products ◽  
National Cancer Center Hospital ◽  
Phase Iii ◽  
Cancer Center ◽  
Off Label Use ◽  
Pharmaceutical Development ◽  
Off Label ◽  
Center Hospital ◽  
Label Use

PURPOSE: In Japan, for pharmaceutical products to be covered by public medical insurance, their efficacy and safety must first be confirmed in clinical trials. To our knowledge, this study is the first investigation into the off-label use of pharmaceutical products at a high-volume cancer treatment center in Japan. The objective of this study is to explore the framework necessary for future pharmaceutical development and regulatory approval in the field of oncology by surveying the frequency of and indications for off-label use of pharmaceutical products at the National Cancer Center Hospital in Tokyo, Japan. MATERIALS AND METHODS: The pharmaceutical products used off-label in daily practice from 2003 to 2015 at the National Cancer Center Hospital were retrospectively examined based on applications that had been submitted to an internal review committee requesting off-label use. RESULTS: A total of 1,390 applications were submitted during the study period. The most frequently used supporting documents were the results of phase II trials, followed by case series and phase III trials. The cancer most frequently treated with off-label drugs was sarcoma (15.1%), followed by urologic cancer (9.2%) and GI cancer (7.6%). CONCLUSION: As reported in previous studies, pharmaceutical products were generally used off-label for the treatment of rare cancers, for which large-scale clinical trials are difficult to conduct. Continued discussion of the types of frameworks that are needed to guide pharmaceutical development is necessary.

Metastatic colorectal cancer (mCRC) patterns of care: Implications for clinical trial design

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4079-4079 ◽  
Author(s):  
C. S. Denlinger ◽  
M. A. Collins ◽  
Y. Wong ◽  
S. Litwin ◽  
N. J. Meropol
Keyword(s):  
Clinical Trial ◽  
Decision Making ◽  
Clinical Trials ◽  
Trial Design ◽  
Clinical Trial Design ◽  
New Drugs ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Treatment Change ◽  
Therapy Regimen

4079 Background: New approaches have expanded options for patients (pts) with mCRC. To characterize current practice paradigms that might bear on clinical trial design, we analyzed decision-making and treatment patterns in pts treated at a Comprehensive Cancer Center since the introduction of cetuximab (CET), and bevacizumab (BV). Methods: A retrospective review of all pts diagnosed with mCRC between 3/1/04 and 8/28/06 treated at Fox Chase Cancer Center. Results: 160 pts were treated, with 157 pts receiving at least one therapy regimen by 10 attending oncologists. There were 350 changes in therapy with 246 (70%) including continuation of at least one prior drug (92 BV, 111 fluoropyrimidines, 43 other). The most common reasons for treatment change were toxicity (33%), progressive disease (PD) (29%), treatment breaks (15%), and metastasectomy (11%) ( Table ). PD was a more common cause for treatment discontinuation in later phases of treatment (18% initial regimen vs. 36% subsequent regimens, p=0.0002). 24% of pts treated with oxaliplatin (OX) discontinued due to neuropathy. Hypersensitivity caused discontinuation in 5% of pts with OX and 7% of pts with CET. Resection of metastases was undertaken in 38% of pts. 43% of these pts received neoadjuvant therapy, and 56% received adjuvant therapy. 30% of pts have died, 29% remain on active treatment, 28% are on a treatment break, 3% are on hospice, and 11% are lost to follow-up. Conclusions: PD is no longer the primary reason for change of therapy in pts with mCRC. Metastasectomy is common and OX neuropathy is often treatment-limiting. These findings have important implications for endpoint selection and design of clinical trials in mCRC. Future clinical trials in mCRC must recognize treatment complexities and capture key components of decision-making that may result in prolonged survival. Furthermore, treatment breaks represent a potential window for the evaluation of new drugs. [Table: see text] No significant financial relationships to disclose.

Large scale training of oncology providers and staff to improve care delivery.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18282-e18282
Author(s):  
Monica Salama ◽  
Joseph Rodgers Steele
Keyword(s):  
Large Scale ◽  
Care Delivery ◽  
Role Playing ◽  
Cancer Center ◽  
Outpatient Services ◽  
Term Care ◽  
Train The Trainer ◽  
Service Excellence ◽  
Md Anderson ◽  
Oncology Providers

e18282 Background: UT MD Anderson Cancer Center began participating in the Press Ganey survey in 2014, and the initial feedback was disappointing. Imaging outpatient services scores were lower than expected, and a difference of opinion between providers and patients was believed to be a contributing factor. Imaging providers defined “care” as the technical quality of the study and the accuracy of the report, while patients associated the term “care” with their healthcare experience. Methods: To improve the patient and family experience and better equip the staff and providers, the Service Excellence Academy (SEA) was created. This ten-hour, three-module program was developed at UT MD Anderson Cancer Center in collaboration with UNLV and MGM Resorts. The program combined didactic and interactive education by leveraging clinical examples and role-playing. A train-the-trainer format was used, including Institutional and Departmental leaders to facilitate the classes. Over 800 participants completed the SEA over 9 months. Questionnaires were administered to the participants before and after the sessions. Results: Since launching the SEA June of 2015, the outpatient Press Ganey scores have improved, and continue their upward trend. All metrics show percentile improvement ranging from 9% to 34%. Additionally, participants felt a greater connection with the institutional mission, vision, and heritage, were more comfortable making decisions, felt more empowered, and had developed greater empathy and skills to meet the needs of others. Conclusions: Large scale training of oncology providers and staff is possible and effective. Implementation of a Service Excellence Academy demonstrated both objective and subjective improvement of patient and employee satisfaction.

Trends in the content and format of main and optional consent forms in oncology clinical trials.

2017 ◽  
Vol 35 (8_suppl) ◽  
pp. 153-153
Author(s):  
Sonja Rummell ◽  
Leo Chen ◽  
Winson Y. Cheung
Keyword(s):  
Clinical Trials ◽  
Reading Level ◽  
Phase Iii ◽  
Cancer Center ◽  
Consent Forms ◽  
Flesch Reading Ease ◽  
Gi Cancer ◽  
Oncology Clinical Trials ◽  
Cancer Studies ◽  
Over Time

153 Background: Informed consent forms (ICFs) should provide prospective subjects with an opportunity to balance the risks and benefits of study participation. However, there are growing concerns about the quality of ICFs. Optional ICFs are also increasingly used as the number of companion studies and biomarker evaluations requiring additional tests become more frequent. We examined trends in the content and format of main and optional ICFs. Methods: ICFs from clinical trials at a tertiary cancer center in British Columbia from 2000 to 2015 were reviewed. We focused on breast or gastrointestinal (GI) cancer studies. Readability was evaluated with the Flesch Reading Ease Score (FRES) and Flesch Kincaid Grade Level (FKGL) where a higher FRES (maximum 100) and a lower FKGL (maximum 12) indicated easier readability. We applied t-tests and linear regressions to examine variations among clinical trials and changes over time. Results: We identified 133 main ICFs of which 70% had optional ICFs and where 57% and 43% were breast and GI cancer studies. Phase III trials (44%), industry funded investigations (70%), and studies involving palliative therapies (72%) were most common. Trials from recent years were more likely to have optional ICFs than those from earlier years (p < 0.001). The median length and median word count in main and optional ICFs were 16 and 6 pages and 6183 and 1862 words, respectively. These changed significantly over time whereby main ICFs increased approximately by 1 page and 364 words per year over the 15 year period (p < 0.001). Industry funded trials also had longer ICFs (p = 0.006). Study methods, risks, and confidentiality occupied 29%, 20%, and 11% of the content on ICFs, respectively. Sections pertaining to eligibility (p < 0.001) and screening procedures (p = 0.007) also increased with time, particularly for industry funded studies (p = 0.006). In terms of readability, optional ICFs were generally more difficult to read than main ICFs (FRES 48.3 vs 50.0, p = 0.024; FKGL 11.8 vs 11.1, p < 0.001), especially in recent years (p < 0.001). Conclusions: This is one of the first analyses to include optional ICFs. Length of ICFs is increasing and readability is discordant with the average reading level of potential trial participants.

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