Peek behind the paper: is high-dose baclofen use associated with increased risk of encephalopathy in individuals with chronic kidney disease?
We peek behind the paper with lead study author Flory Muanda (Institute for Clinical Evaluative Sciences; ICES, Ontario, Canada) to further understand how researchers investigated the association between high-dose baclofen and encephalopathy in older individuals with chronic kidney disease (CKD).
In 2019, we reported on the results of a novel study suggesting that individuals with chronic kidney disease prescribed a high dose of baclofen are more likely to be hospitalized for severe confusion or disorientation compared with individuals not prescribed the drug, or prescribed a low drug dose.
In this feature, we peek behind the paper with lead study author Flory Muanda (Institute for Clinical Evaluative Sciences; ICES, Ontario, Canada) to further understand how researchers investigated the association between high-dose baclofen and encephalopathy in elder individuals with chronic kidney disease (CKD).
Please could you introduce yourself and your affiliate institution?
I am currently a postdoctoral fellow at the Institute for Clinical Evaluative Sciences, Kidney Dialysis and Transplantation Program, which is a world-renowned institute for health service research.
My research program aims to reduce the risk of medication errors in patients with CKD. This is a major public health concern since many medications used in this population are eliminated by the kidney and evidence to inform safe prescribing is lacking in the literature.
What prompted you to conduct this research?
Peter Blake, a co-author of this study and a nephrologist at Victoria Hospital (Ontario, Canada), observed several cases of encephalopathy in renal patients who started baclofen. This prompted Amit Garg – senior study author also affiliated with the ICES – and I to initiate this study to better characterize the risk of encephalopathy associated with the use of baclofen in CKD patients, using a more robust design.
How did you define your study cohort and what limitations may these inclusion criteria impose on your study results?
Our cohort included adults aged 66 years and older with CKD who were newly dispensed oral baclofen from an outpatient pharmacy between January 2007 and March 2018.
One of the biggest challenges of using real-world evidence is to accurately collect information on exposure, outcomes and potential cofounders using healthcare databases, which are not purposely designed to do research."
One of the limitations resulting from this definition of our study population was that we could not include younger adults in our study, since this population does not receive universal prescription drug coverage in Ontario.
As such, our findings may not apply to younger adults. However, approximately half of the patients described in the case report studies we analyzed were younger than 66 years.
What are some of the challenges associated with employing real-world data sources, such as patients’ hospital records, and what limitations may these impose on the results of your study?
One of the biggest challenges of using real-world evidence is to accurately collect information on exposure, outcomes and potential cofounders using healthcare databases, which are not purposely designed to do research. In this study, we used International Classification of Diseases, 10th Revision (ICD-10) codes, which were entered in the main diagnosis field of the database, to identify cases of encephalopathy. This field contains a single diagnosis that most influenced patients’ lengths of hospital stay and/or is responsible for the greatest proportion of resource use.
By doing this, we are cognizant that we captured the most severe cases since we did not capture cases of encephalopathy occurring in outpatient settings, for example. Therefore, we are conscious that we have likely underestimated the true estimates of the risk of encephalopathy associated with the use of a high dose of baclofen.
Clinicians should be aware of the risk of encephalopathy associated with the use of baclofen in patients with CKD."
In addition, information on patients’ serum baclofen levels was not available in our laboratory database; this precluded any corroboration, in this study, that excessive serum concentrations of baclofen caused observed encephalopathy. As such, we expect some misclassification in the outcome of encephalopathy in this study since our codes are likely insensitive, however there is no reason to believe that misclassification occurred differentially between exposure groups.
What do you hope some of the implications of your research may be; how do you hope clinicians and regulators may respond to your research?
Clinicians should be aware of the risk of encephalopathy associated with the use of baclofen in patients with CKD. If baclofen is prescribed, especially in patients with low kidney function, clinicians should always balance the risk of encephalopathy against the benefits of its use. When prescribed, the dose should be low and appropriate for the level of kidney function.
Regulatory agencies...should consider issuing warning labels to alert prescribers of the study findings."
Patients and their families should be warned about what they might experience after starting the drug. If a patient with chronic kidney disease is admitted to hospital with confusion, when reviewing the medication list, clinicians should consider whether baclofen is a potential culprit. Regulatory agencies such as Health Canada (Ottawa, Canada) and the US FDA should consider issuing warning labels to alert prescribers of the study findings.
Do you have future studies planned in this field?
Our aim is to prevent medication errors in patients with CKD, since robust evidence is currently lacking for this population who is often excluded from clinical trials. We are currently examining the risk of encephalopathy associated with the use of baclofen in patients receiving maintenance dialysis.
Flory Muanda is a recipient of a Canadian Institutes of Health Research (CHIR) and Mitacs postdoctoral award. Muanda has no conflict of interest to declare.
The opinions expressed in this feature are those of the interviewee/author and do not necessarily reflect the views of The Evidence Base® or Future Science Group.