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Treatment Efficacy for Single Conditions Unaffected by Comorbidities

Clinicians are often uncertain as to whether treatments for single conditions might be affected by the presence of comorbidities. A new analysis of clinical trial results by a research team led by the University of Glasgow has now provided reassurance.

The researchers noted that the "confusion" about how therapy for single conditions should be applied in people with multiple chronic conditions stemmed, in part, from the fact that people with multi-morbidity are under-represented in clinical trials, which rarely report whether treatment efficacy differs by the number of comorbidities or the presence of specific comorbidities. The lack of empirical estimates of treatment effect modification by comorbidity has lead to "uncertainty in treatment recommendations", they said.

Their study, published in PLOS Medicine , used existing individual participant data from 120 industry-sponsored randomised controlled phase 3 and 4 clinical trials carried out between 1990 and 2017. The dataset included a total of 128,331 participants and spanned 23 common long-term conditions, including asthma, diabetes, hypertension, osteoporosis, and migraine. 

Across the trials, the percentage of participants with three or more comorbidities ranged from 2.3% in allergic rhinitis trials to 57% in trials for systemic lupus erythematosus.

The trials were not designed to assess variation in treatment efficacy by comorbidity. The team modelled whether there were any interactions between treatment efficacy and comorbidities for each trial, as well as each treatment type spanning multiple trials.

No Evidence of Comorbidities Modifying Treatment Efficacy

Overall, they found "no evidence of comorbidities modifying treatment efficacy across any of the 23 conditions studied", and no evidence that treatment efficacies were affected by the number of comorbidities. This was the case for 20 conditions for which the outcome variable was continuous (such as change in glycosylated haemoglobin in diabetes) and for three conditions in which the outcomes were discrete events (such as number of headaches in migraine), although for some conditions (for example corticosteroids for asthma) credible intervals were wide.

"The standard assumption used in evidence syntheses is that efficacy is constant across subgroups, although this is often criticised," the authors said. "Our findings suggest that for modest levels of comorbidities, this assumption is reasonable."

Results Could Help to Inform Clinical Guidelines

Lead author Peter Hanlon, clinical research fellow in general practice & primary care at the University of Glasgow, said: "Many people live with multiple long-term conditions; however, deciding on the most appropriate treatment for these people is often challenging because clinical trials rarely report whether treatments work as well in people with multiple conditions, and clinical guidelines rarely address the specific needs of these people. 

"We found that treatments had similar effects in people with multiple conditions, which is important as this information can be used to help experts decide which treatments they should recommend in clinical guidelines."

Asked to comment by Medscape News UK, Professor Kamila Hawthorne, chair of the Royal College of General Practitioners said: "GPs are expertly trained to deliver holistic, complex care for those with multiple physical and mental health conditions and will always consider each individual's circumstances when developing a treatment plan. 

"As with all latest research, it is important that the findings of this latest study are considered when updating clinical guidelines. 

"We also need to consider the impact polypharmacy has on patients, as many drugs interact with each other, not necessarily for the good of individuals.

"While it’s a wonder of modern medicine that patients are living for longer - as they do; they are often living with multiple, chronic health conditions, and this in turn means the demand for general practice care has grown in both volume and complexity."

More People Living with Multiple Conditions

Also commenting for Medscape News UK, Dr Jennifer Harris, director of research policy at the Association of the British Pharmaceutical Industry, said: "The proportion of patients living with two or more medical conditions is rising, so we need a better understanding of the causes of multi-morbidity and approaches to new treatments.

"As this study points out, a key challenge is the way in which clinical trials are designed and regulated, which generally follows a ‘condition-specific’ framework.

"We believe this can be overcome, and we are determined to work creatively with regulators, funders and patients to do that."

This work was funded by the Wellcome Trust and the Medical Research Council. SD received fees from the Association of the British Pharmaceutical Industry for delivery of a Masterclass unrelated to this work. The other authors have declared no competing interests.