Clinical trials are used to demonstrate the efficacy and safety of promising investigational therapies, procedures, or medical devices prior to receiving regulatory approval. In every clinical trial, there is a natural tension between two competing objectives: The desire to exclude certain patients who have co-existing (or co-morbid) health conditions and the desire to fully understand the full safety and efficacy of the therapy in patients.
Co-morbidities are other health conditions that a patient may be managing in addition to the health condition being studied in the trial. Common co-morbidities that would warrant exclusion from trial participation include renal (kidney) dysfunction, hepatic (liver) dysfunction, diabetes, cardiovascular disease, hypertension, obesity, cancer, asthma or chronic obstructive pulmonary disease, HIV, and more.
It is widely believed that trial participants who are managing one or more co-morbidities may affect the results of the trial, for a variety of reasons:
The price of exclusion
When strict criteria are used to exclude patients who have one or more co-morbidities, trial sponsors and investigators are able to more easily analyze the results of the trial and discuss conclusions about safety and efficacy. However, when individuals with specific co-morbidities are underrepresented in the population of enrolled patients, the clinical findings developed during the trial will not necessarily be generalizable to the more diverse patient populations that are likely to be prescribed the medication in real world healthcare settings once the new medication has received regulatory approval and is on the market.
When this happens, important safety insights and other potential adverse effects that may occur in patients with specific co-morbidities may not be detected until a larger population of actual patients begins using the medication. While post-marketing studies collect and analyze real world evidence over time, data may not be gathered and analyzed as rigorously and systematically as it would be in a formal trial setting.
While the specific impact varies with the type of comorbidity and the therapy being studied, the presence of one or more co-morbidities in patients enrolled in a clinical trial can impact the outcome of the trial in several ways:
- Patients may face challenges coordinating or tolerating multiple medications, or may experience more adverse events. This may not only skew the findings of the trial, but may undermine the trial participant’s ability to remain adherent to therapy.
- Specific co-morbid conditions, such as diabetes or heart disease, or impaired liver or kidney function, can impact how a medication is metabolized by the body.
Today there is increasing interest in designing clinical trials that better reflect broader, more diverse real world patient populations. This will give patients who are managing one or more co-morbidities broader access to clinical trials (and promising new therapy options) that may benefit them. It would also help trial investigators and regulators to develop a deeper understanding of the new therapy’s clinical efficacy and safety profile in a more diverse range of patients.
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