Surgical trials are infrequently performed, underpowered, and risk significant selection bias as patients who are deemed surgical candidates have already undergone one level of selection. Furthermore, the process of translating bench research into clinical practice can take significant time, with prior studies estimating that it takes 17 years to move a concept from bench to bedside. With significant time demands from moving from phase I to phase III trials come significant monetary costs. Dr. Uzzo notes that “the estimated average pre-tax industry cost per new prescription drug approval is $2.558 million.” Another raised issue is the use of surrogate endpoints. For example, 18 of 36 drugs approved by the FDA between 2008-2012 reported no improvements in overall survival and only 1 reported improvement in quality of life. Lastly, a major issue with clinical trial findings is that they are not implemented by practicing physicians.
So how should clinicians begin involvement in clinical trials? Dr. Uzzo explained the importance of finding clinical questions that are personally interesting and clinically relevant; answering such questions through scientific inquiry will help physicians to develop a philosophy and guiding principles. He advised physicians to look for influencers, particularly those outside of the field of urology, who can inspire research questions. For clinicians who ultimately perform clinical trials, it is important to understand one’s role as a shareholder and responsibility of representing many stakeholders; a principal investigator must successfully manage a myriad of roles and responsibilities at once.
Getting involved in clinical trials has certain standard requirements (such as those imposed by the FDA), and specific institutional requirements. Standard requirements such as general clinical investigator (PI) responsibilities are outlined by Title 21 and can be found on the FDA website. Other requirements can be institution-specific, and getting involved with the Office of Clinical Research (OCR) is the initial step. The OCR will help investigators navigate the process, obtain initial and additional training, understand the institutional requirements necessary before conducting a trial, form, and train research teams. While the OCR tends to a significant proportion of the details, ultimately the PI is responsible. Additionally, it is important to define and develop clear staff roles (research coordinators, data specialists), and to empower the staff so that the team can work most efficiently and productively.
Lastly, Dr. Uzzo reviewed some important “don’ts” of clinical trial work before concluding his talk.
DON’T:
- Over-designate to non-physicians
- Erase, obliterate original data entry
- Accept suggested changes without checking the source documents or without justification for changes
- Backdate consent forms
- Forget to obtain IRB approval of consent form revisions
- Revise the protocol without obtaining the sponsor’s written concurrence
- Use staff as subjects
- Destroy study records
Presented by: Robert G. Uzzo, MD, MBA, FACS, Chair, Department of Surgical Oncology, Division of Urology and Urologic Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
Written by: Selma Masic, MD, Urologic Oncology Fellow (SUO), Fox Chase Cancer Center, @selmasic, at the 20th Annual Meeting of the Society of Urologic Oncology (SUO), December 4 - 6, 2019, Washington, DC