Ethics in musculoskeletal regenerative medicine; guidance in choosing the appropriate comparator in clinical trials.
BACKGROUND
Regenerative Medicine (RM) techniques aimed at the musculoskeletal system are increasingly translated to clinical trials and patient care. This revolutionary era in science raises novel ethical challenges. One of these challenges concerns the appropriate choice of the comparator in (randomized controlled) trials, including the ethically contentious use of sham procedures. To date, only general guidelines regarding the choice of the comparator exist.


OBJECTIVE
To provide specific guidelines for clinical trial comparator choice in musculoskeletal RM.


METHODS
In this manuscript, we discuss the ethics of comparator selection in RM trials. First, we make a classification of RM interventions according to different health states from disease prevention, return to normal health, postponing RM treatment, supplementing RM treatment, substituting RM treatment, improving RM outcome, and slowing progression. Subsequently, per objective, the accompanying ethical points to consider are evaluated with support from the available literature.


RESULTS
a sham procedure is demonstrated to be an ethically acceptable comparator in RM trials with certain objectives, but less appropriate for musculoskeletal RM interventions that aim at preventing disease or substituting a surgical treatment. The latter may be compared to 'standard of care'.


CONCLUSION
From a scientific perspective, choosing the correct comparator based on ethical guidelines is a step forward in the success of musculoskeletal RM.
['de Windt|T S|TS|', 'Niemansburg|S L|SL|', 'Vonk|L A|LA|', 'van Delden|J M|JM|', 'Roes|K C B|KCB|', 'Dhert|W J A|WJA|', 'Saris|D B F|DBF|', 'Bredenoord|A L|AL|']
D018450:Disease Progression D032984:Ethics, Research D006801:Humans D007258:Informed Consent D009140:Musculoskeletal Diseases D018579:Patient Selection D016032:Randomized Controlled Trials as Topic D044968:Regenerative Medicine D012107:Research Design D018570:Risk Assessment D033581:Stem Cell Transplantation
Ethics Musculoskeletal Regenerative medicine Clinical trials Sham Stem cells