Background
Main text
Approval and monitoring of innovative pharmaceuticals in North America and the central role of the industry-funded, placebo-controlled randomized controlled trial (RCT)
The process of development for innovative surgical procedures
Phase/Stage | Pharmaceutical Innovation | Surgical Innovation |
---|---|---|
0 | ▪ Preclinical animal studies used to characterize the pharmacology of the agent as well as its safety across a dosage range ▪ Used to support creation of an IND application, which is submitted to the FDA or Health Canada | ▪ Initial prehuman (simulator or animal) work and development, which may be reported as preclinical studies |
1 | ▪ Phase I RCTs conducted within a small group of health volunteers to assess the safety, tolerability, accepted dosage range, and pharmacokinetics of the IND after one or more doses | ▪ Technical skills development and/or acquistion and proof of both concept and safety, which may be described in structured case reports |
2 | ▪ Phase II RCTs that administer the drug over its anticipated target dosage range to patients with the target health condition to assess feasibility and/or the infleunce of the drug on a biomarker or biomarkers | |
2a | ▪ Although the technical details of the surgical procedure have not been completey refined, a few surgical practice leaders have adopted the technique and are using it on a small group of patients outside the index hospital or center where it was originally developed ▪ May be described in prospective development studies | |
2b | ▪ Many of the technical details have been nearly perfected, and the surgeons who adopted the procedure in stage 2a start to broaden patient accrual and procedural indications ▪ May be described in cohort studies, diagnostic performance studies, and RCTs | |
3 | ▪ Phase III RCTs designed to assess the efficacy or effectiveness of the medication in patients with the target health condition on a series of pre-defined efficacy and safety endpoints | ▪ The innovative procedure is now becoming part of many surgeon’s practices, and only a select few will not have adopted it ▪ May be evaluated in RCTs or other studies where clinical equipoise exists |
4 | ▪ Post-marketing studies conducted to monitor for rare adverse effects or to assess the usefulness of the agent among other patient populations or when administered in different dosage forms | ▪ Long-term monitoring studies whose aim is to assess for unexpected rare outcomes and restrict or expand indications for the procedure or clarify additional important technical details |
The contrasting pattern of RCT use for the evaluation of surgical innovation
Challenges in using RCTs for the evaluation and regulation of surgical innovations
Differences in the process of innovation for surgical procedures versus pharmaceuticals
Methodological and technical challenges for use of RCTs for surgical evaluation
Unique challenges for the conduct of RCTs in trauma and emergency surgery
Lack of external validity among published surgical RCTs
Evidence-based surgery and surgical history, education, training, and culture
Academic surgery, methodological expertise, and research funding
Present systems for regulation of innovative surgical procedures
The IDEAL recommendations for evaluation and monitoring of surgical innovation
Conclusion
A recommended approach to the evaluation, monitoring, and regulation of innovative surgical procedures
Research Methods and Funding Challenges | |
▪ Increased funding opportunities (alone and within research teams) and expert methodological support for surgical researchers ▪ Increased support by Departments of Surgery and their members to recruit, support, and retain academic surgeons ▪ Increased use of RCT (including pragmatic, adaptive, tracker, expertise-based, or cluster), experimental or quasi-experimental (parallel group, non-randomized, controlled interrupted time-series studies, or stepped wedge designs by surgery or site), and comparative effectiveness studies for evaluating surgical innovations (guided by the above methodological experts) (where RCTs are either unethical or impractical) ▪ Increased use of the IDEAL recommendations for evaluating surgical innovations by surgeons, institutions, scientific journals, and other stakeholders ▪ Editors of surgical journals and professional surgical societies should mandate that studies of surgical innovations be reported according to the EQUATOR guidelines and that EQUATOR checklists are uploaded with studies when submitted for peer-review ▪ Increased conduct and reporting of economic analyses of surgical interventions to determine their cost-effectiveness (ideally these studies would be “piggy-backed” to RCTs comparing an innovative to a conventional surgical procedure) | |
Surgical History, Education, Training, and Culture | |
▪ Integration of formal education on evidence-based medicine knowledge and skills into surgical residency training programs ▪ Increased CME and surgical journal series on evidence-based surgery topics for staff surgeons and surgical trainees ▪ Increasing the number of surgeon and non-surgeon researchers in Departments of Surgery with formal training in research methodology ▪ Increased support by surgical opinion leaders on a shift towards a culture of surgical practice that is based on evidence and apprenticeship ▪ Use of knowledge translation interventions that embrace that surgical practice changes and the use of evidence in surgery may occur more effectively when championed or supported by surgical practice leaders ▪ Research to better understand the methods by which surgeons make decisions and decide to implement or de-implement evidence-informed practices into or out of surgery |