CHAPEL HILL, NC, UNITED STATES - Mar 3, 2014 - Rho
Offers Tips for Decreasing Missing Data in Analgesia Clinical
Chapel Hill, NC ̶ DATE
̶ Rho, a contract research organization (CRO) focused on
bringing new products to market through a full range of product
development services, offers tips on how to limit the amount of
data that goes uncollected during pain trials.
"Missing data can be a very serious challenge in clinical
trials, particularly with pain trials," said Karen Kesler, Ph.D.
and senior statistical scientist for Rho. "Drop outs often
occur in pain trials because side effects and a lack of
efficacy. If you're on the control arm and you're not getting
pain relief, you're much more likely to drop out of the study,"
added Dr. Kesler.
The National Academy of Sciences issued a report in 2010 on the
prevention and treatment of missing data in clinical trials that
has shaken up the status quo on how to deal with missing
data. FDA just issued a draft guidance for analgesic
indications, but the recommendations about missing data, while
sound, are not very specific. Below, Rho provides tips on how
to decrease missing data through study design and study
Tips to Decrease Missing Data
- Study Design Strategies:
- Consult with experts and practitioners during study design
about aspects of the protocol that may negatively impact subject
- Instead of the typical parallel arm study, consider other study
designs. The FDA is open to enrichment or titrate-to-effect
designs that might work well for your compound.
- Have a dialogue with the FDA early on in the program
development and be plugged into the FDA pain division at the design
stage about your method for analyzing missing data. It is
unlikely they will accept last observation carried forward (LOCF),
so be prepared for the need to conduct more complex analyses.
- Keep patient assessments simple. Collect only the data points
you need to support your analysis, and try to limit the number of
visits that will be required of the patients.
- Document a plan in the protocol for dealing with subject drop
outs rather than reacting to issues as they occur.
- Attempt to continue collecting data on subjects that stop
taking study drug.
- Try to work rescue medications into your design instead of
having those subjects who need them drop out of the study.
Sometime you can use the pain scores prior to a rescue medication
and keep that subject in your analysis.
- Study Design Options
- Put subjects on increasing doses of active and control arms
until they achieve pain relief.
- Can provide more information about dosing and subject
- Reduces dropout due to lack of pain relief as subjects continue
to increase until they achieve pain relief.
Randomized withdrawal designs
- Start with everyone on active dose, after a set period of time,
randomize subjects who achieve pain relief to move to placebo or
stay on existing dose
- Your end-point comparison is at the end of second
post-randomization period or time to resumption of pain
- Minimizes dropout rate due to not receiving analgesia because
everyone starts with it
- Patients are more likely to buy into this design; you can
shorten the period of follow up to reduce the amount of people you
could lose after randomization
How a study is executed can also
contribute to the reduction in missing data. Below are study
execution tips from Rho:
- Consider the burden on patients when determining how patient
reported outcomes will be collected (i.e., paper diary, ePRO)
- Site selection is critical. The selection process should
be robust and comprehensive
- High level of attention to data collection is crucial
- Staff training is key
- Having a properly trained staff is particularly important in
pain trials because you are using pain scales that require subject
- Site needs to be able to instruct patients properly to get
- Site needs to know how to review data they are receiving from
patients to make sure it is accurate
- Advise sites to review patient diaries before subject leaves
- Communicate with the subject between visits. This helps
manage subject population to maintain patients and prevent drop
To learn more about Rho, please visit www.rhoworld.com.
Rho, a privately-held, contract research organization (CRO)
located in Chapel Hill, NC, provides a full range of clinical
research services across the entire drug development process. For
more than 25 years, Rho has been a trusted partner to some of the
industry's leading pharmaceutical, biotechnology, and medical
device companies as well as academic and government organizations.
Our commitment to excellence, our innovative technologies, and our
therapeutic expertise accelerate time to market, maximize returns
on investment, and lead to an exceptional customer experience.
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