Oct 24 2012

Considerations for the Assessment of Pain in Non-Verbal and Pediatric Subjects

Image credit: Flickr user Chalky Lives

Studies of drugs, biologics or devices that are intended for use in pediatric populations fall under far more stringent guidelines than those intended for use in adults.  The issues with pediatric studies range from informed consent concerns to stricter risk-to-benefit analyses.  Another problem that can arise in these studies, is that very young children cannot adequately verbalize simple ideas such as how much pain they are experiencing.  The following is a discussion of some of the considerations when deciding on pain assessment instruments for clinical trials involving pediatric subjects, with particular attention to those for use with non-verbal subjects.

Pain assessment is an important tool not only in medical care of patients in the hospital, but can also be critical for clinical trials in which reduction in pain is a goal.  The typical way to assess pain in a research setting is to use validated pain scales. These instruments are designed to rate pain levels in a statistically useful way.  While expressions of pain may seem obvious at first glance, accurate assessments can be confounded by the subjective manner in which people perceive pain.  In the case of alert, verbal subjects, assessment can be fairly straightforward.  Many pain scales simply ask the patient to visually or verbally indicate how they rate their pain.  That rating is converted to a numerical value that can be compared to other subjects’ scores in a statistically meaningful way.  This form of pain scale qualifies as a patient-related outcome, or PRO, in the context of clinical trials and is regulated by the related guidances and regulations.  The second form of assessment is proxy assessment of pain.  In proxy assessment, the level of pain is rated by someone other than the subject, usually a relative or professional caregiver.

When looking at the assessment of pain in non-verbal pediatric subjects it becomes immediately apparent that the latter type of pain assessment is the only option.  A child who cannot speak or understand speech cannot tell you how much something hurts.  As a result, any study involving pain in non-verbal pediatric subjects will be forced to use proxy assessment of pain.  This form of assessment comes with its own challenges above and beyond the subjective nature of pain perception.  There are numerous proxy assessment scales that may or may not be appropriate for any given study. Each will have its benefits and its problems.

The first question that must be examined when choosing any pain scale, whether in verbal or non-verbal subjects, is the nature of the pain being assessed. Is the pain acute or is it chronic.  A pain scale may have been found valid for acute pain but may be less appropriate for chronic pain.  It is important to pay attention to the types of pain for which a scale has been validated. In addition, some pain scales have been developed specifically for certain conditions or diseases and therefore might be inappropriate in other settings.  For instance, a scale validated to assess pain associated with ear aches might not translate to a study on post-operative pain.

The next thing to consider when selecting a pain assessment instrument is the age of the children that will be assessed.  Again, this is important regardless of whether or not the subjects are verbal, but in the case of non-verbal pediatric subjects it is critical.  There are specific pain scales that have been developed for newborns and very young infants that are not appropriate for older children.  Likewise some pain scales developed for toddlers and older infants may have criteria that are inappropriate for very young infants.  The Pediatric Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (Ped-IMMPACT) has examined the  age ranges for which a variety of observational (i.e. proxy-assessed) measures of pain have been appropriately validated. When looking for an age appropriate pain scale their work is an excellent place to start.  The Ped-IMMPACT study lists the types of pain that the scales have been validated to assess, helping to alleviate the problem discussed above with selecting the appropriate scale for a given pain type.

In addition to the type of pain and the age of the children in question, there is the question of who is the best person to make proxy assessments of pain. Studies have shown that there are a wide variety of biases that can arise based on who is assessing pain. Factors that have been shown to affect pain assessment range from the gender of the assessing person to the age of the subject being assessed. This fact leads to the question: should the pain assessment be carried out by a physician or nurse caregiver or should it be done by a parent? One can imagine that first time parents with a very young infant might assess pain in their child very differently than a pediatrician or neonatologist that has worked with children for 20 years.  In some cases, however, parents or guardians have been shown to have very good understanding of the pain levels of their child.  Some pain assessment instruments state explicitly that a parent should administer the assessment, while others require diagnostic criteria that only a professional caregiver is qualified to measure.  In those cases the choice is clear.  However, when it is not explicitly built into the instrument, the identity of the proxy will have to be decided based on the available data on the pain scale and the recommendations of regulatory agencies.

Regulatory agencies will demand validated pain scales for clinical trials in which pain is being assessed at any age or level of communication. Unfortunately, validation is another area where observational or proxy pain assessment scales for use with non-verbal subjects is more complicated. In the case of verbal patients, observational pain assessment instruments can be correlated with self-assessment instruments. Validation by comparison to self-reported pain has some pitfalls but it is a clearer case than when the subject cannot confirm an assessment.  Validation can be achieved by comparison of new proxy-assessed pain scales with older proxy-assessed pain scales, as well.  Additionally, validation can be gained from inter-rater correlation studies.  Inter-rater correlation is defined as the similarity in assessment between different assessors of the same subject.  Theoretically, a high inter-rater correlation indicates that the pain assessment instrument is at least consistent, even if the correlation speaks less to absolute accuracy of the instrument.  It is also sometimes possible to carry out the pain assessment using a new instrument in verbal children who can then self-report their pain.  The correlation of the new proxy-assessed instrument with self-reported pain is then used to extrapolate to younger children or non-verbal subjects.  This approach can be problematic, however, due to potentially different perception of pain between ages.  Ultimately, the absolute criteria for validation of a pain assessment instrument in the context of clinical trials are going to lie with the opinion of the regulatory agency under which the trials are being carried out.

There are numerous other considerations when picking a pain assessment scale for use in a clinical trial.  Many of these are shared between all scales regardless of the subject population. These considerations would include the difficulty of actually performing the assessment.  Overly complex assessments that take a great deal of time could lead to poor compliance during the trial and decreased accuracy of assessment.  If instructions are not clear the assessments could be flawed by misunderstanding.  These are general questions that apply to all studies, not just pediatric studies, however.

Pain assessment and alleviation has become a key issue both in the arena of clinical trials and in the everyday care of patients in clinical settings.  Thankfully, the number of pain assessment instruments in general, and specifically for non-verbal subjects, is increasing.  The validity of these scales are now being carefully, clinically tested to ensure that they truly reflect the pain experienced by the subject.  Frequently, those who are most vulnerable to pain are unable to voice their suffering.  Very young and even older non-verbal subjects fit into this category. The choice of pain scale in any study has numerous considerations.  However, these considerations are further blurred when dealing with an at risk population such as non-verbal children and therefore require even more careful thought and planning.

This post was written by Nick Osborne, Ph.D.  Nick is a Scientist at Cato Research.