In this morning’s asthma news, an announcement was made that a Phase 2a (the patient “pilot” phase of a study)1 clinical trial in the United Kingdom for an asthma drug was halted by the sponsoring pharmaceutical company2. In the case of the research study in question, the inhaled medicine was to be used to prevent worsening of asthma when a virus was contracted—think a common cold, bronchitis, something of that nature—by powering up the “antiviral defenses” of cells in the lungs of people with asthma, which do not fight illness as well as the lungs of people without asthma.2 (And all the asthmatics said “Ahh, it makes sense why I get sick more than other people now!) Now, of course, it’s extremely disappointing as a patient to see a trial stop—the new shiny things will take longer to become new shiny things I can actually use!—and just imagine if you were a patient in the trial!
Good reasons for clinical trials ending early
However, if a trial ends early (which of course does not mean it has ended forever!), there are usually very good reasons for this to happen. In another article, the reason for discontinuation of the study was that cold viruses did not cause as many severe asthma exacerbations as was anticipated by the company who developed the drug.3 My thought is also that it would be rather difficult to produce an adequate sample of participants who had both asthma and developed a cold during the study period, and were aware of and actively involved in the trial. Simply put, to participate in a clinical trial, enough screening tests must be done to establish a baseline of the patient, ensure that they actually have asthma, and then roll forward with testing the investigational drug—or placebo. I can see how in a study that relies on both asthma and presence of a cold virus it would be difficult to get an adequate sample, and then also determine the specific populations within that sample that the drug in question actually works for3.
Why else might a clinical trial suddenly hit the brakes? In large scale trials (which is becoming practice in all clinical trials) a data monitoring committee continuously reviews patient data as it comes in for trends.4 If the data monitoring committee determines that there is a difference in benefit, or greater risk to patients in the trial than anticipated (as in, these risks are more significant than simply chance), a trial may be halted.4 Some trials have pre-specified “stopping guidelines”, which means that when the criteria is met (such as the study intervention is not determined to be a better choice than existing interventions, or there are risks to the patient that can no longer be deemed as chance) the trial ends.5 Data monitoring committees act as advisory committees and their input is extremely valuable but does not necessarily mean that a study will stop or continue.4 Another reason a trial may end or be delayed is an inadequate number of eligible participants is posing detriment, as the rationale to halt the trial as above, the study may be canceled as insufficient data will be produced by the study to adequately prove the efficacy of the drug and patient safety outcomes.3
Drawbacks of ending a clinical trial too early
There are drawbacks to ending a clinical trial early, which is why the process is not taken lightly. How will we know long-term effects of the drug in question, and if they do in fact have an impact on long-term survival or quality of life, if the study is halted suddenly, such as in a heart attack treatment study?5 What options are patients who were benefitting from the study drug left with—what if a patient experienced great benefit from an investigational drug from a clinical trial, and had to suspend treatment because of negative outcomes they have not experienced, and may never experience? How are they cared for at the—maybe even sudden seeming—end of the trial period? A key question is one that is essentially rooted in ethics: What is done with the data from the patients collected so far, and how will it be used that still ensures the data has benefit? How might the data participants have generously and patiently donated, and research physicians and their assistants spent hours pouring over, have an impact still?5 What will patients be informed of upon completion of a trial—either successful completion or an unexpected termination? These answers are different for each person, and each clinical trial, and may be worth considering if you are participating in a clinical trial—especially in its early stages.
Clinical trials will only be halted with good reason—there is a lot of time, data, money and so forth on the line (and those are in no particular order!) for every person involved in a trial, from the patient to the drug manufacturer, to the pharmaceutical company, to the doctors and nurses and research staff involved. There’s a lot riding on this decision—especially when there could be yet discovered benefit to an investigational treatment. However, when they do end, it is usually with good reason, and with the best of intentions: patient safety, by being able to deliver solid evidence that the treatment works, who it works for, and at what level of risk.