Don’t Let Summer Obstacles Catch You Off Guard

In research, anytime variation is introduced and unaccounted for, it can mask the true results of an intervention. Variation can come from seasons, meaning that clinical trials should be accounting for this. The summer season can contribute to variation and can introduce other specific challenges to a clinical trial. Some of these challenges may also appear during the winter months, and fortunately, the same solutions apply.

We humans are different creatures in the summertime. We eat differently, we exercise more (or less) than during other parts of the year, and we spend more time outdoors. Changes in our biochemistry can result. In a clinical study, all of these differences can turn into confounding factors, or factors that are actually responsible for differences in study results that falsely appear to be due to the treatment or intervention. For example, vitamin D, which is produced in the body during sun exposure, is generally found in higher concentrations in the blood during the summer. Vitamin D acts as a hormone that influences many different physiological processes. Cholesterol can also change with the seasons. With any biomarker or clinical endpoint that varies by season, if some participants are enrolled during the summer while others are enrolled during the winter, this can contribute to undesirable variation in baseline data or differential responses to treatment. Medical events also occur more frequently in some seasons compared with others; this can directly impact study results.

There are also logistical challenges to running a trial during the summer months. The many holidays and ensuing vacations during the summer months can slow and delay communication between sponsors, investigators, and participants. This in turn can result in missed milestones. Multinational studies may also experience additional holidays from other countries. Some participants report that the summer season can negatively affect their compliance with a treatment, and it is not necessarily because of vacations. Separately, going on vacation can also affect compliance, and being away from home means that participants must take care to store their medication appropriately (i.e. refrigeration). In patients with chronic diseases who are hospitalized, the length of hospital stay can be longer in the summer.

There are ways to combat these added challenges when running a clinical trial. Most of these solutions must be implemented during the planning stages of a study, but there are often creative solutions for rescuing a trial failing for seasonal reasons.

• Plan ahead. Be sure to design meetings, conference calls, site visits, and participant study visits around all possible holidays, considering national holidays of all involved countries and allowing extra time for things to get done during popular vacation months. Use data from study sites to predict how participant compliance may be affected during certain months at certain sites.

• Screen more strictly. If sun exposure is going to directly interfere with an intervention, such as in a dermatological study, it may be a good idea to exclude people who spend a lot of time outdoors. This data can be collected at a screening appointment and used to determine eligibility. To ensure better rates of compliance, some studies employ a run-in period prior to randomization with the sole purpose of making sure participants will complete their assigned study activities.

• Enroll more participants and account for these factors statistically. If it is not justifiable to exclude participants based on factors that will interfere with study results, it may be best to enroll more participants to be able to run adequately powered subgroup analyses. Similarly, if a low level of compliance is expected or even detected during the study, more participants can be enrolled to compensate. As a last resort and with appropriate FDA and/or IRB approval, sample sizes can be increased after a trial has already begun.