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What to do with negative results clinical research – and why they don’t equal failure

by | May 3, 2023

It can be disappointing if your trial generates negative results; you may feel it has been a waste of time and resources. But negative results do not necessarily mean failure.

If you’re facing negative results and wondering what to do next, it can be helpful to consider the value you and the wider scientific and medical world can gain from those results. Especially given the cost of failure: a failed phase III trial does not only cost the resources it took to run that trial, but all the research leading up to it too, plus efforts to explore an alternative intervention.

Failure is costly but common. Negative results may not be what you had hoped for, but there are ways you can make sure they contribute to the body of knowledge about the intervention on trial and the target it was aimed at.

Here we look at how we define failure, how to take a different perspective, and what you can do with your results.

When does a clinical trial fail?

Clinical trials are complex, often unpredictable, and frequently unsuccessful. Because of the wide range of clinical trial designs, phases, and approaches, success and failure can look different depending on your context and perspective. The success of each trial is evaluated according to the predefined goal of the research: its endpoint.

The endpoint of a trial could be clinical, such as the improvement in symptoms or survival rates, or surrogate, such as biomarker changes that reflect slower disease progression. A trial may have several other goals to meet in order to continue, including reaching a certain number of participants and demonstrating the safety of the intervention on trial.

If a trial fails because it could not finish, there may be little valuable output beyond sharing learnings for design or recruitment in future trials. But if the trial fails because of adverse effects or because it shows the intervention is ineffective, those results can be a valuable part of a bigger story.

The problem with obscuring negative results

Until recently, it was relatively uncommon to publicize negative clinical trial results – the intervention failed after all; what would be the use? In fact, obscuring negative results can have a significant impact – and it can cost billions of euros.

Non-publication means a piece of information about an intervention is not included in our body of knowledge. Imagine a phase II trial of a potential small cell lung cancer drug showed no clinical benefit: a negative result. The results are stored away instead of being shared or discussed, which means they are not included in any systematic reviews or meta-analyses of treatments.

Because there is no information available on the unsuccessful drug, reviews give an unintentionally misleading impression that it could have potential, so another research team decides to trial it. Their trial follows the same path, costing time and resources that could have been directed to a different treatment.

If that second set of negative results are also left unpublished, the picture becomes even more skewed over time, creating a publication bias.

This sounds unlikely, but it can happen. Despite a push toward clinical trial transparency and the registration of trials and their results, a large proportion of trial results remain hidden. Between March 2018 and September 2019, the results of less than 41% of trials registered on were submitted within a year, even though this is a legal requirement.

The value of negative results

Negative results have particular value for three groups: patients, researchers, and the broader scientific world.

Patients – negative results can provide important information about the safety and efficacy of a treatment; if you share the results, you can help prevent harm to future patients who may take part in a duplicate trial. And participants of a trial expect the results to be published.

Researchers – by sharing your ‘failure’ you can help other researchers avoid repeating the research with the same negative results, saving time and resources. Negative results can also be a source of inspiration for researchers, so you could spark the next big treatment approach.

Broader scientific world – your negative results become part of the bigger story about the intervention and the disease it targeted. And by publishing negative results, you are also strengthening transparency and accountability in clinical research.

How you can advance scientific knowledge

Depending on your location and where you carried out the trial, regulation may require you to register and publish your results – for example, in the US, all results must be registered at You also have additional options to share your results beyond that.

You could consider uploading the results to a data repository or publishing on a preprint server such as bioRxiv or medRxiv. Many peer-reviewed journals accept negative results, including topic-specific journals like Trials and BMC Research Notes, and broad open-access journals like PLOS ONE.

However you decide to share your negative results, it is important to do it transparently and to describe the study design, methods, and results clearly. This way you can be sure your ‘failure’ has value and contributes to the advancement of science.

Will you set your trial up for success? Find out how working with Siron Clinical can help.


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