Written by: Gerald L. Klein, MD; Roger E. Morgan, MD; Shabnam Vaezzadeh, MD; Renu Jain, PhD; Pavle Vukojevic, MD; Burak Pakkal, MD; Michael Fath, PhD; Larry Florin, MBA; Victoria Manax, MD; L. Allen Kindman, MD
Drug, Device, and Diagnostic Development
It is extremely difficult to demonstrate statistical significance and efficacy in clinical trials. The placebo and nocebo effects, which appear to be increasing in randomized clinical trials, begin to account for some of these difficulties.[1] Caliskan et al. state, “Placebo effects can enhance the efficacy of a treatment through positive treatment expectations, wherby nocebo effects can induce side effects or abolish the treatment effect through negative treatment expectations. Addressing and optimizing patient’s expectations as well as previous experiences about a treatment could improve patient’s adherence and compliance to a therapy.”[2]
By providing clear and unbiased information, it may be possible to limit the negative impacts of both the placebo and nocebo effects. A centrally supplied video informing patients of the positive and negative aspects of the test product and clear outline of the study may help decrease this problem; this process would allow for more effective patient treatment in the future.
The FDA’s New Key Information Section for Informed Consent Forms (ICFs) recommends that the most important information be presented in the beginning of the form in a key information section.[3] The agency recommends that key information be presented in a bubble format. The FDA provides examples as shown in Appendix A.
Similar to the role filled by all Data and Safety Monitoring Board (DSMB) members, we strongly recommend that all clinical trials employ an independent medical monitor. A medical monitor that has direct ivolvement in the study or any other conflict of interest, including but not limited to, financial, proprietary, or professional interests, via the sponsor has built in bias.[4] For example, one NIH division recommends that an independent physician safety monitor be used in clinical trials.[5] Implementing unbiased reviews can elevate the quality benchmarks for clinical trials, product development, and the overall industry.
Medical Affairs
Establishing and running a medical affairs organization can be a significant financial burden on small commercial pharma and biotech companies. The use of a lower cost program that provides strategic goals can ease the financial burden on smaller commercial enterprises. This practice supplements the marketing and sales plan until more economic resources are available for growth. The following are examples of such activities:
Targeted communication plan - publishing in less expensive open access journals and then promoting them on social media offers a realistic alternative to high-cost publication and advertisements.
Case histories, series, and review articles - these forms of publication support your product in medical literature and help to drive conversation and traffic surrounding the product.
Low-cost clinical studies - studies including quality of life, real world data, and registries may be of value to smaller medical affairs programs.
The use of a limited number of medical liaisons that can be used to target key opinion leaders (KOLs) that are interested in the product and active in the community. KOLs must be interested in supporting the product with papers, presentations, and other scientific activities.
Your medical affairs small program can also focus on less expensive clinical studies such as quality of life, real world data, and registries.
The use of fractional medical affairs members as opposed to full time employees can provide an experienced staff at a fraction of the cost.
Appendix A
[1] Vase, Lene. "Can insights from placebo and nocebo mechanisms studies improve the randomized controlled trial?" Scandinavian Journal of Pain, vol. 20, no. 3, 2020, pp. 451-467. https://doi.org/10.1515/sjpain-2019-0183
[2] Caliskan, Elif Buse*; Bingel, Ulrike; Kunkel, Angelika. Translating knowledge on placebo and nocebo effects into clinical practice. PAIN Reports 9(2):p e1142, April 2024. | DOI: 10.1097/PR9.0000000000001142
[3] https://www.fda.gov/media/176663/download
[4] https://www.nidcr.nih.gov/research/human-subjects-research/independent-safety-monitor-guidelines