Integrating value of research into NCI Clinical Trials Cooperative Group research review and prioritization: A pilot study

BackgroundThe Institute of Medicine has called for approaches to help maximize the return on investments (ROI) in cancer clinical trials. Value of Research (VOR) is a health economics technique that estimates ROI and can inform research prioritization. Our objective was to evaluate the impact of using VOR analyses on the clinical trial proposal review process within the SWOG cancer clinical trials consortium.MethodsWe used a previously developed minimal modeling approach to calculate VOR estimates for 9 phase II/III SWOG proposals between February 2015 and December 2016. Estimates were presented to executive committee (EC) members (N = 12) who determine which studies are sent to the National Cancer Institute for funding consideration. EC members scored proposals from 1 (best) to 5 based on scientific merit and potential impact before and after receiving VOR estimates. EC members were surveyed to assess research priorities, proposal evaluation process satisfaction, and the VOR process.ResultsValue of Research estimates ranged from −$2.1B to$16.46B per proposal. Following review of VOR results, the EC changed their score for eight of nine proposals. Proposal rankings were different in pre‐ vs postscores (P value: 0.03). Respondents had mixed views of the ultimate utility of VOR for their decisions with most supporting (42%) or neutral (41%) to the idea of adding VOR to the evaluation process.ConclusionsThe findings from this pilot study indicate use of VOR analyses may be a useful adjunct to inform proposal reviews within NCI Cooperative Clinical Trials groups.The Instiztute of Medicine has called for approaches to help maximize the return on investments in cancer clinical trials. The findings from this pilot study indicate use of value of research analyses may be a useful adjunct to inform proposal reviews within NCI Cooperative Clinical Trials groups.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146484/1/cam41657.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146484/2/cam41657_am.pd

Breast MRI in the Diagnostic and Preoperative Workup Among Medicare Beneficiaries With Breast Cancer

We compared the frequency and sequence of breast imaging and biopsy use for the diagnostic and preoperative workup of breast cancer according to breast MRI use among older women

Against quantiles: categorization of continuous variables in epidemiologic research, and its discontents

<p>Abstract</p> <p>Background</p> <p>Quantiles are a staple of epidemiologic research: in contemporary epidemiologic practice, continuous variables are typically categorized into tertiles, quartiles and quintiles as a means to illustrate the relationship between a continuous exposure and a binary outcome.</p> <p>Discussion</p> <p>In this paper we argue that this approach is highly problematic and present several potential alternatives. We also discuss the perceived drawbacks of these newer statistical methods and the possible reasons for their slow adoption by epidemiologists.</p> <p>Summary</p> <p>The use of quantiles is often inadequate for epidemiologic research with continuous variables.</p

Feasibility study of a clinically-integrated randomized trial of modifications to radical prostatectomy

<p>Abstract</p> <p>Background</p> <p>Numerous technical modifications to radical prostatectomy have been proposed. Such modifications are likely to lead to only slight improvements in outcomes. Although small differences would be worthwhile, an appropriately powered randomized trial would need to be very large, and thus of doubtful feasibility given the expense, complexity and regulatory burden of contemporary clinical trials. We have proposed a novel methodology, the clinically-integrated randomized trial, which dramatically streamlines trial procedures in order to reduce the marginal cost of an additional patient towards zero. We aimed to determine the feasibility of implementing such a trial for radical prostatectomy.</p> <p>Methods</p> <p>Patients undergoing radical prostatectomy as initial treatment for prostate cancer were randomized in a factorial design to involvement of the fascia during placement of the anastomotic sutures, urethral irrigation, both or neither. Endpoint data were obtained from routine clinical documentation. Accrual and compliance rates were monitored to determine the feasibility of the trial.</p> <p>Results</p> <p>From a total of 260 eligible patients, 154 (59%) consented; 56 patients declined to participate, 20 were not approached on recommendation of the treating surgeon, and 30 were not approached for logistical reasons. Although recording by surgeons of the procedure used was incomplete (~80%), compliance with randomization was excellent when it was recorded, with only 6% of procedures inconsistent with allocation. Outcomes data was received from 71% of patients at one year. This improved to 83% as the trial progressed.</p> <p>Conclusions</p> <p>A clinically-integrated randomized trial was conducted at low cost, with excellent accrual, and acceptable compliance with treatment allocation and outcomes reporting. This demonstrates the feasibility of the methodology. Improved methods to ensure documentation of surgical procedures would be required before wider implementation.</p> <p>Trial registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00928850">NCT00928850</a></p

Prioritizing research: the use of risk prediction, value of information analyses, and portfolio evaluation to improve public investments in cancer clinical trials

Thesis (Ph.D.)--University of Washington, 2014Background: Fewer than half of all medical interventions in use today are supported by clinical evidence. Despite allocating more than $11 billion each year to support clinical research, federal funding for medical research lacks a coordinated system for prioritizing and allocating resources to efficiently address these important knowledge gaps. The Institute of Medicine recently stressed that rigorous prioritization of trial concepts for large cancer clinical trials cooperative groups was critical to ensure that limited public funds are used effectively and efficiently. Yet despite this ardent call to improve the means of prioritizing and selecting cancer clinical trials, many questions remain about how to achieve these goals. Portfolio management is a systematic approach to decision-making that is widely used in the private sector to inform and manage research investments. Yet despite it's conceptual simplicity, this approach has not been used to inform publicly funded cancer clinical trial investments because of the difficulty in defining and measuring risk and return in this setting. In this dissertation, I therefore developed and evaluated quantitative measures of risk and return that were appropriate for National Clinical Trials Network-sponsored trials and applied a proof of concept portfolio evaluation approach to a sample of clinical trial proposals recently reviewed by a large cancer clinical trials cooperative group, SWOG. Methods: In Chapter I, I developed a statistical model to predict the risk of an accrual feasibility failure, defined as a trial that does not enroll a sufficient number of patients and consequently is unable to inform clinical practice patterns, based on trial-level variables available before the trial is launched, and evaluated its internal validity. In Chapter II, in collaboration with key stakeholders I developed a process to efficiently quantify the societal return of the proposed studies using Value of Information (VOI) methods and evaluated its feasibility and acceptability. Lastly, in Chapter III, I estimated the predicted risk and expected return for a sample of recently reviewed clinical trial proposals to illustrate how a portfolio management framework could inform funding decisions within a cancer clinical trials cooperative group setting. Results: In Chapter I, I provide a comprehensive and empirical assessment of risk factors that are associated with and predictive of a clinical trial that does not meet 50% of its target accrual. I identified several novel predictors, and showed that these predictors in combination with several established risk factors could predict which NCTN-sponsored clinical trials were at highest risk of poor accrual. In Chapter II, I describe several key changes that I made to the traditional Value of Information analysis framework to accommodate SWOG stakeholders preferences and facilitate timely calculation. The efficient and pragmatic process that I developed leveraged information included in each trial proposal and reported the expected health benefits and incremental healthcare costs associated with acquiring additional information separately. In Chapter III, I illustrate how a portfolio management approach provides a means of efficiently summarizing both the expected accrual feasibility and societal return - two critical criteria - for a large sample of trial proposals simultaneously and therefore provides a framework for evaluating trial concepts against one another. Conclusions: I found that a portfolio evaluation is a feasible and potentially useful response to the IOM's call for more systematic approaches to select and prioritize trial concepts against one another. The approach can facilitate the ranking of a large number of trial concepts simultaneously using two key criteria for which I developed novel methods to estimate, and also inform longer-term strategic decision-making. A portfolio evaluation approach could therefore help decision makers select and prioritize cancer clinical trial concepts that have the greatest potential to improve population health and thereby optimize the return on limited research funds

Platinum Priority -Prostate Cancer Individualized Estimation of the Benefit of Radical Prostatectomy from the Scandinavian Prostate Cancer Group Randomized Trial

a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e u r o p e a n u r o l o g y . c o m Article info Article history: Accepted April 5, 2012 Published online ahead of print on April 18, 2012 Keywords: Prostatic neoplasms Statistics and research design Randomized controlled trial Prostatectomy Please visit www.eu-acme.org/ europeanurology to read and answer questions on-line. The EU-ACME credits will then be attributed automatically. Abstract Background: Although there is randomized evidence that radical prostatectomy improves survival, there are few data on how benefit varies by baseline risk. Objective: We aimed to create a statistical model to calculate the decrease in risk of death associated with surgery for an individual patient, using stage, grade, prostatespecific antigen, and age as predictors. Design, setting, and participants: A total of 695 men with T1 or T2 prostate cancer participated in the Scandinavian Prostate Cancer Group 4 trial (SPCG-4). Intervention: Patients in SPCG-4 were randomized to radical prostatectomy or conservative management. Outcome measurements and statistical analysis: Competing risk models were created separately for the radical prostatectomy and the watchful waiting group, with the difference between model predictions constituting the estimated benefit for an individual patient. Results and limitations: Individualized predictions of surgery benefit varied widely depending on age and tumor characteristics. At 65 yr of age, the absolute 10-yr risk reduction in prostate cancer mortality attributable to radical prostatectomy ranged from 4.5% to 17.2% for low-versus high-risk patients. Little expected benefit was associated with surgery much beyond age 70. Only about a quarter of men had an individualized benefit within even 50% of the mean. A limitation is that estimates from SPCG-4 have to be applied cautiously to contemporary patients. Conclusions: Our model suggests that it is hard to justify surgery in patients with Gleason 6, T1 disease or in those patients much above 70 yr of age. Conversely, surgery seems unequivocally of benefit for patients who have Gleason 8, or Gleason 7, stage T2. For patients with Gleason 6 T2 and Gleason 7 T1, treatment is more of a judgment call, depending on patient preference and other clinical findings, such as the number of positive biopsy cores and comorbidities