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Risk Based Monitoring (RBM) Lessons From Research Predicting Autism In Infants

By Penny Manasco - June 5, 2018

I recently read an interview with Oren Miron, a biomedical informatics research associate at Harvard and winner of the 2017 Next Einstein Competition researcher.  He repurposed a standard technology used to test an infant’s hearing for autism.  
Research from the 1970’s by Professor Hildesheimer showed that children with autism had a consistently delayed response to Auditory Brainstem Response (ABR) tests.  Autism was thought to be a disease of the frontal cortex, so this finding was “lost” in many ways until Miron found the published research.  
MRI had become the method of diagnosis.  A fine tool but prohibitively expensive to use as a screening tool.
Miron looked for a low-cost way to screen for autism and found it in a test now used routinely to test for hearing loss.   He screened thousands of infants for hearing loss and compared the results with the data on subsequent autism diagnosis and found a consistent response.  He is now searching for funding to conduct a prospective trial to validate his findings.
Finding children with autism early allows intervention to begin years earlier than 4 years old, the average age a child is diagnosed with autism.  This can significantly enhance a child’s life by what can be accomplished through early intervention.
This teaches us RBM lessons as follows:
  1. The tools to conduct RBM are in place and the data are available, but it is HOW you look at the data that affects what you find.  The tools to collect and analyze the critical data (e.g., EDC/eSource, ePRO, CTMS, Protocol-Specific reporting) are available—just like the ABR responses unique to autism were there—it took an inquisitive, scientific mind to “see” the pattern and recognize its significance.
  1. Scientific discipline is needed to evaluate the utility of new tools.  Miron used pre-existing data to conduct the first hypothesis testing, which he is following with prospective trials.  

We, in the clinical research arena, need to use the same scientific discipline to evaluate the optimal way to conduct oversight of trials.  We can’t keep using the methods, such as SDV, as our only means to evaluate trial quality. SDV has been proven to be ineffective; a position reiterated in Guidance by the Regulatory authorities.  We owe it to scientists everywhere to use the same scientific rigor in conducting clinical trials to prove the efficacy and safety of their important scientific discoveries and to help achieve the ultimate goal of improving patients’ lives.
We need to implement analytic approaches to determine whether the experiment (protocol) was performed correctly.  Did the right person, trained to conduct the experiment, conduct the experiment?  Were controls included for the primary endpoints?  In scientific experiments, we include positive and negative controls to be sure the experiment was performed correctly.  In clinical trials, placebo or active controls are often used for this purpose.  But research scientists review all aspects of the experiment (e.g., reagents, procedures, and analysis approaches) before expressing confidence in the results.  We, in clinical research, need to adopt and use the same approach.
MANA RBM is committed to advancing the scientific discipline of clinical research. We have, and will continue to validate and publish the findings and analysis of our proprietary methods for trial oversight. Links to the Journals and copies are/will be available on our website.
We have previously published data on approaches superior to SDV and eCRF review, remote Informed Consent Review, Site Responses to Paperless trials, using electronic Investigator Site Files for Paperless trials, and monitor competencies for RBM.  Please contact us if you would like a copy of any of these papers or a link to it.
Stay tuned; we have many interesting papers that will be published in the near future, including a prospective comparison of SDV and a remote trial management approach.
Please join the mailing list on our website so we can notify you when these important papers are published and released.  Join us, also, as MANA RBM pioneers the field of Clinical Operations as a scientific discipline in lockstep with the scientists designing and developing our new treatments.