The Importance of Multi-Faceted Quality Assurance in Alzheimer’s Disease Trials

feasterBy Todd Feaster, PsyD, Clinical Program Scientist for Alzheimer’s Disease at Bracket

Rater Training is a well-accepted best practice for most Alzheimer’s disease trials; but ongoing ratings scale and clinical outcomes Quality Assurance is still only implemented intermittently, and there is an ongoing discussion about the best ways to conduct this QA.

Worksheet and ratings reviews are the most common methods; paper documentation QA, confirmation of score totals based on worksheets, and in many cases review of supporting materials, such as drawings and other performance based tasks. There are several good reasons to expand these reviews to more rigorous audio and video reviews of patient interviews, informant interviews, and cognitive testing. However, it can be expensive and cumbersome.

poster-dataNext week at the Alzheimer’s Association International Conference in Toronto, Bracket will be presenting new data on how these audio reviews can supplement other, more passive quality assurance measures. Outcomes that rely on subjective patient interviews are still at risk for noise or incorrect data being entered into an EDC. Adding audio reviews of scale administrations enables detection of additional errors that are not apparent on worksheet review alone, thereby further improving data quality over the course of a trial.

A few examples of errors that may only be identified through an audio or video review of a clinical interview or cognitive test include;

  • Incorrect prompts or help offered by a rater to a patient having difficulty answering a question.
  • Incorrect tabulation of the number of words remembered during a word recall test.
  • Incorrect time allotted for time-based performance tasks.

video controlPast research has demonstrated the clear improvement that eCOA can have on data quality. Nevertheless, the use of eCOA for difficult, subjective rating scales like the ADAS-Cog and CDR-SB should still be combined with a comprehensive training program and ongoing quality assurance.

To learn more about how Bracket can combine Rater Training, eCOA, and Quality Assurance for your AD program, stop by booth 524 at AAIC in Toronto, or Contact Us to schedule a demo.

Site Selection and Alzheimer’s Disease

Identify, selecting, and preparing clinical trial sites to conduct a clinical trial is an ongoing struggle for sponsors looking to run bigger and more global clinical trials.

7-13-2016 12-40-05 PMFor some indications, this can be an especially tricky proposition. Increasingly, pivotal phase 3 trials in Alzheimer’s disease are required to screen, and eventually randomize, exceptionally large numbers of patients. The result has been the requirement for a very large number of centers to be identified, globally, for every new program. An analysis of currently recruiting, industry-sponsored, phase 3 intervention trials listed in ClinicalTrials.gov shows an average of 67 centers open for each trial, and 7 studies with more than 100 centers.

Bracket has traditionally focused on providing technology to investigators that will allow them to better collect outcomes data in these trials. And in training and certifying the sites and site personnel who will execute a trial. However, there are things that can be done even before this happens that will improve your chances of signal detection in your trial.

The selection of investigative sites to participate in clinical trials is often focused on evaluation of historical therapeutic experience, past subject recruitment and regulatory compliance records. However, in these difficult trials, we already know the very subjective Clinical Outcomes Assessments can be difficult to administer, and identifying sites, investigators, raters who have demonstrated competency with these instruments in past studies can be a meaningful strategy.

At Bracket, one approach we’ve taken is to bolster traditional site feasibility data with additional metrics utilizing historical clinical outcome assessment administration performance data. In research that was presented at the 2015 Clinical Trials on Alzheimer’s Disease Conference (CTAD) conference in Barcelona, sites were able to be stratified using this performance data, giving sponsors an additional criteria to assist in their evaluation.

alzheimer

A Methodology for Evaluating Clinical Trial Sites and Raters Based on Performance Data – CTAD

Since potential recruitment numbers, and past recruitment experience, is so important to the feasibility process, it’s important to evaluate recruitment in the context of these performance data as well.

alzheimerThe evaluation of clinical outcome performance criteria can be an important component of improving study execution. In this study, a methodology was developed to evaluate historical experience and clinical outcome administration performance data as a mechanism to enhance site and rater selection. Historical data shows only a limited correlation between sites with high or low performance quality, and sites with high or low recruitment rates. So combining both factors in your feasibility process is essential. And in some cases, it can still be valuable to invest the time in initiating a site that may have very limited recruitment, if you can have greater confidence that they will enroll good patients, and provide high quality data.

Later this month, at the Alzheimer’s Association International Conference in Toronto, Bracket will be presenting some of our most recent data evaluating how we can help support your global clinical trials. To schedule a demonstration or time to discuss these tools and services, please use the contact form.

Register Now: Disruptive Innovations in Data Analytics in CNS Clinical Trials

Register now for Bracket’s upcoming webinar on utilizing data analytics in CNS clinical trials, presented by:

admin-ajax Alan Kott, MUDr, Clinical Vice President and Practice Lead, Data Analytics, Bracket

daniel-david David G. Daniel, MD, Senior Vice President and Chief Medical Officer, Bracket, and Professor of Psychiatry, George Washington University

Measurement error and data recording errors (including data fabrication) (Baigent, 2008) are frequent and often non-randomly distributed in clinical trial datasets. Even when accumulated at a single site or a small number of sites their impact may be devastating to the success of a CNS clinical trial. It is therefore critical to identify those sites and raters who are at greatest risk of providing erroneous or otherwise compromised data.

Fig1_Any Data Quality ConcernCentral statistical monitoring techniques have been shown to successfully identify fraudulent/fabricated data in clinical trials using objective outcomes (Knepper, 2016) but have been less effective in clinical trials using subjective outcome measures such as psychiatric rating scales (O’Kelly, 2004). It is however exactly these ‘subjective outcome’ trials that are in the greatest need of effective data quality monitoring programs.

At Bracket, we have successfully implemented risk-based data quality monitoring programs (Blinded Data Analytics) in a number of CNS clinical trials across numerous indications. These programs combined near real time central statistical monitoring approaches with comprehensive clinical review and where indicated targeted follow-up with the identified raters/sites. In many of these CNS clinical trials, central statistical monitoring worked in concert with intelligent eCOA and remote audio/video monitoring programs.

In this webinar, we will discuss examples of identified data quality concerns coming from CNS clinical trials and the impact of their presence on study outcomes. We will show that many of the data quality concerns are clustering at a small number of centers and many post-randomization data quality concerns can be predicted by the occurrence of similar concerns in the screening period. We will conclude by demonstrating the positive impact of implementing eCOA and remote audio/video monitoring programs on data quality.

To reserve your spot, register now.