Invited Review
Rethinking Follow-Up Durations in Surgical Clinical Trials: The Case for Short-Term Assessments in Rapid Innovation Environments
Kai-Uwe Lewandrowski, MD
Center for Advanced Spine Care of Southern Arizona
Tuscon, AZ
Mauricio G. Pereira, MD, PhD
University of Brasilia, Faculty of Medicine, Brasilia, Federal District
Brasilla, Brazil
Alexandre Siciliano, MD
Department of General and Specialized Surgery, Gaffrée e Guinle University Hospital, Federal University of the State of Rio de Janeiro (UNIRIO)
Rio de Janeiro-RJ, Brazil
Abduljabbar Alhammoud, MD
Department of Orthopaedic Surgery, University of Arizona College of Medicine
Tucson, Arizona
John C. Elfar, MD
Department of Orthopaedic Surgery, University of Arizona College of Medicine
Tucson, Arizona
Sergio Luis Schmidt, MD, PhD
Department of Neurology, Federal University of the State of Rio de Janeiro (UNIRIO)
Rio de Janeiro, Brazil
Paulo Sérgio Teixeira de Carvalho, MD, PhD
Pain and Spine Minimally Invasive Surgery Service at Gaffrée Guinle University Hospital
Rio de Janeiro, Brazil
Morgan P. Lorio, MD, FACS
Advanced Orthopedics
Altamonte Springs, FL
Stenio Karlos Alvim Fiorelli, MD, PhD
Head of Angiology and Vascular Surgery Service at Gaffrée e Guinle University Hospital
Três Rios - RJ, Brazil
Marcos Arêas Marques, MD
Angiology and Vascular Surgery Service, Gaffrée and Guinle University Hospital of the Federal University of Rio de Janeiro (UNIRIO)
Rio de Janeiro, Brazil
Sandoval Lage Sobrinho, MD
Department of General and Specialized Surgery, Gaffrée and Guinle University Hospital, Federal University of the State of Rio de Janeiro (UNIRIO).
Rio de Janeiro, Brazil
Rossano Kepler Alvim Fiorelli, MD, PhD
Department of General and Specialized Surgery, Gaffrée e Guinle University Hospital, Federal University of the State of Rio de Janeiro (UNIRIO)
Rio de Janeiro-RJ, Brazil
Introduction
The two-year follow-up standard in clinical trials, particularly in the context of drug and therapeutic evaluations, has its roots in both historical practices and regulatory requirements. Many clinical trials, especially in fields like oncology and chronic diseases, have used two years as a benchmark for assessing the medium-term effectiveness and safety of a treatment. In some medical specialties, this follow-up period is considered long enough to observe significant outcomes and potential side effects or adverse reactions that might not be apparent in the short term. The two-year follow-up requirement is also mandated by regulatory agencies like the US Food and Drug Administration (FDA)1-3 and the European Medicines Agency (EMA).4
While using a standard time frame may allow for easier comparison across studies, a relatively longer duration of follow-up may delay the implementation of novel procedures whose benefit or failure may be apparent within a few weeks or months. Additionally, longer follow-up periods, like those extending beyond two years, present both ethical and practical challenges.5 Long-term follow-up studies also require extended commitment from subjects and can increase the complexity and cost of a clinical trial. Progression of the underlying chronic disease process may also washout the treatment effect of the intervention, further confounding an accurate assessment of treatment efficacy.
On the surface, a two-year, follow-up period appears to strike a balance between gathering long-term data and practical feasibility. Clinical experience and past research often guide the decision on the follow-up period. In some cases, it may be wise to choose two years based on the natural history of the disease being studied and the expected timeframe for accurate cause and effect determination. While two years is a common standard, the appropriate follow-up duration may vary and could be adjusted depending on the specific objectives and nature of each trial. Some conditions and their surgical treatments may only require shorter follow-up periods to adequately address the research questions or meet regulatory requirements.6