The Challenge and Management of Clinical Trials in Integrative Cancer during the COVID-19 Pandemic Worldwide

Since the rapid spread of novel coronavirus disease (COVID-19) in 2020 worldwide, it has been a great challenge to launch clinical trials in most countries, especially for integrative cancer therapies due to the close-contact interventions and the frequent follow-up. It is estimated that the drop-out rate of clinical trials during the COVID-19 pandemic was about 70% to 80%, and we also predict that the next 5 years might witness a sharp fall in the number of the clinical trials of integrative cancer therapies. Thus, it is significant to propose some countermeasures to improve the quality of current and future clinical trials of integrative cancer therapies and protect subjects participating in the clinical trials, as more complementary and alternative medicine (CAM) in randomized controlled trials (RCTs) of cancer were conducted and published in the recent years before 2020. ¹

COVID-19 forces most hospitals in the epidemic areas to significantly reduce non-emergency admissions and services, which led to the fact that it is difficult to treat cancer patients involved in clinical trials, including during recruitment and follow-up. ² To address these problems, the sponsor, principal investigators, and CAM physicians should be encouraged to postpone or suspend those clinical trials with close-contact therapies such as acupuncture and massage. ³ For pharmaceutical therapies, it is convenient for researchers to send the investigated products to the subjects by express delivery.

Telemedicine technology such as telemedicine consultations and electronic data capture (EDC) have multiple benefits for cancer patients in clinical trials, as EDC could be comprehensively built and used for follow-up and safety evaluation instead of traditional involving face-to-face assessments done on paper. ⁴ In the future, integrative cancer care may need to rely more on telemedicine services, such as consultations with integrative physicians and remotely delivered mindfulness or exercise therapies. ⁵ For Yoga, Tai Chi, Qigong, meditation, and other mind-body therapies, the best way of participating in a clinical trial might be to stay at home under the instruction of telemedicine services, and feedback information by EDC.

With the advent of COVID-19 vaccines, we suddenly face to new problems, in addition to the safety of vaccines themselves. For integrative cancer therapies, we may need to focus more on the interaction between vaccines and high-dose vitamins, minerals, or Chinese herbs, as the ingredients of multi-component herbal and supplement formulas are too complicated. Here, we also appeal to investigators to avoid the combination of COVID-19 vaccines and herbs or supplements for at least a 4-week period, until we could access to evidence-based observations for safety.

To launch new clinical trials in integrative cancer care, the extent, design, outcome, follow-up, and safety evaluation might be quite different from the conventional ones in the period of COVID-19. The development of protocols and pathways in this field is necessary. Concerning design, open-label, single-center, and distant-contact intervention would be more suitable and safe; likewise, overall survival time, quality of life, and other scales would be better options for outcome instead of an index that needs to be investigated with CT or MRI imaging and blood tests. Additionally, real world studies, cohort studies, and pilot RCTs might be promoted as the limitations on these studies are fewer than those on RCTs.

In conclusion, COVID-19 has necessitated a dramatic change in the way we do clinical trials in integrative cancer therapy. To better manage clinical trials and protect subjects, more detailed guidelines and expert consensus documents should be set up as soon as possible, and the wide use of vaccines should be also taken into consideration. We hope that our suggestions might be useful for the management of clinical trials in integrative cancer therapy during the epidemic of COVID-19.