Clinical trials are used to test how novel treatments compare with already existing treatments or their potential to cure a new disease. The main goal of medication is the significant impact on patient care, which requires several test phases to ensure that this goal is achieved. However, not all clinical trials end up like planned.

To start with, there are two dimensions why clinical trials fail. Firstly, project failures can be a reason, which includes budget, project targets and deadlines that must be met. The second dimension is research failure, for example not being able to reach statistical significance in a research area. Within those dimensions, there are basic principles that must be paid attention to.

What are these main aspects that can cause failures in clinical trials?

One reason for failures are molecules that don’t work. This means, that the molecule either doesn’t have enough biological activity or doesn’t have manageable toxicity. In some cases, we can find no biological activity at all, whereas in others there is some, but the effects are not like expected. In addition to that, every molecule has toxicity in it that the trialist has to design around. The problem here is not the toxicity itself, but rather if it has unpredictable effects.

Moreover, another cause for clinical trial failures is the inability to meet predetermined timelines or criteria. The FDA provides several rules and expectations for novel treatments, which some companies neglect. Those companies that do not meet the requirements from the FDA can risk their chance to get their treatment passed to later phase clinical studies. In consequence, this results in abandonment of the newly created medication.

However, one of the most common reasons for failure are design issues. The most important variables for clinical trial design are the selection of the right patient, the right dosing and the right endpoint. The right endpoint matters to ensure that a new drug is of essence and shows the desired effects. When a novel treatment goes to clinical trial, certain characteristics of a good endpoint must be checked. Characteristics, such as clinical relevance, reliability and robustness to dropouts & missing data.

Secondly, the right dose, such as amount of an intervention, route of administration, interval dosing and the duration of administration play an important role. The most common mistake with dosing is selecting a dose that is too high or too low. This case can occur, when previous studies weren’t thorough enough to collect sufficient data.

The last parameter for a good endpoint is the right patient. Patients that are physically incapable of responding to the treatment result in poor patient selection. It’s vital to think through the disease you want to cure and maybe even expand the trial, in order to check all disease categories that are relevant.

There are many reasons for clinical trial failure and those are just 3 of them. All in all, test periods for novel medications take a long time and precise analysis of various criteria. In order to successfully pass all test phases of a clinical trial, many aspects must be considered and thought through carefully.

For examples of clinical trial fails from the year 2017, click here.

References:

• Chris Palford (July 8, 2015). Why Do Most Clinical Trials Fail. Available at: https://www.clinicalleader.com/doc/why-do-most-clinical-trials-fail-0001
• Richard Chin (November 13, 2017). Why Clinical Trials Fail. Available at: https://clinicaltrialist.com/2017/11/13/why-clinical-trials-fail/
• Artem Andrianov. (May 2, 2015). 7 Reasonst Why Clinical Trials Fail. Available at: https://cyntegrity.com/7-reasons-clinical-trials-fail/