In the world of scientific research, negative findings are sometimes viewed as a disappointment, especially in large studies that require significant effort, time, and expense. A ‘negative finding’ means that the study did not find the results that were expected or hoped for, meaning that the hypothesis being tested was not supported by the data collected. However, it's important to remember that negative findings do not indicate a “failure”, because they are valuable to identify what doesn't work, leading to new questions and unexpected answers. 

The LEEP Study

The American Lung Association's Airways Clinical Research Centers (ACRC) recently published a major study called the Losartan Effects of Emphysema Progression (LEEP) in the American Journal of Respiratory and Critical Care Medicine. This work is important because there is currently no treatment that can slow down the progression of emphysema, a type of COPD that is characterized by irreversible destruction of the air sacs in the lungs, leading to shortness of breath.

The LEEP study investigated the efficacy of the drug losartan in slowing the progression of COPD-related emphysema in the lungs. Losartan is a drug that is used to treat high blood pressure and heart failure. Previous studies in both animals and humans showed potential for losartan to slow or stop the destruction of lung tissue that is typically seen in patients with emphysema. 

The study was a placebo-controlled trial of losartan for people with mild to severe COPD, which means that some research volunteers received the drug, and others received a placebo, which is usually a sugar pill with no pharmacological effect. A placebo control is important to separate the effects of the drug from any effect from just participating in a clinical trial. The researchers hoped that losartan could slow the rate of progression of emphysema, as measured by high-resolution imaging of the lungs. 

Unfortunately, the results of the study did not show evidence that losartan slowed the development of emphysema. But this does not necessarily mean that losartan has no effect on emphysema in general. Researchers who conducted the study think that patients in their study had a slower-than-expected progression of emphysema. In other words, the control group who did not receive the drug did not get as sick as expected.  

Sparking a conversation

The outcome of the ACRC LEEP trial was highly anticipated by the research community. After publication of the study, other colleagues published a letter in response to the study, offering comments and suggestions around the findings, particularly in how study participants were selected or identified. 

This kind of public correspondence is a useful way to share new perspectives or potential mechanisms that will ultimately improve on the next research study. In fact, the LEEP study authors included some of their own perspective in response, providing additional context and considerations for other readers in the community. In the end, it makes the practice of science more transparent, elevates the standards of quality, and can also spur new studies. 

Asking new questions

The LEEP trial had some unexpected benefits outside of their main research question, including generating other research publications. A portion of the research volunteers participated in an additional study aimed at understanding the impact of the COVID-19 pandemic on people with COPD. Since the volunteers were already enrolled in a longitudinal study, they were already in regular contact with researchers, so it was easy to collect additional data.

Their main finding was that patients in the study experienced lower levels of isolation and high levels of social support, and many participants reported that they very much enjoyed the study interviews and looked forward to them. It is possible that participation in the study itself lead to improved outcomes of depression and anxiety. So, while the results of this study were not directly related to the outcomes of the LEEP study, these results were critical to understanding how COPD patients were coping with the COVID-19 pandemic.

Part of the process

While negative findings could be perceived as a failure, they are an essential part of the scientific process. In fact, many would argue that negative findings are just as important as positive findings. Normalizing the publication of negative findings encourages other researchers to publish their findings, regardless of the outcomes.  

Despite not finding the expected outcome, the information from the LEEP study is incredibly valuable as it helps to better understand losartan treatments and will steer future research in the right direction. The publication of negative trials also stops doctors from keeping people on medications that they (as a medical community) think might work, but don’t; thus, sparing patients from side effects and unnecessary costs. 

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