Coping with an embarrassment of riches. How stroke centers may participate in multiple, concurrent clinical stroke trials.
BACKGROUND
The recent remarkable proliferation of multicenter clinical trials investigating novel treatments for acute ischemic stroke has created a new dilemma for stroke investigators. Promising agents and trials are many, competent clinical centers few. May a single clinical center, without scientific bias, participate in multiple, concurrent clinical trials recruiting overlapping populations of subjects with acute stroke?


RESULTS
Many clinical stroke centers already participate in multiple overlapping trials. I delineate a variety of patient-allotment strategies that are presently used, although often not explicitly stated. Methods include assignment by time window, unique criteria, site, belief in agent efficacy, remuneration, and quota urgency. All have drawbacks, chiefly the introduction of bias into the selection of subjects for clinical trials, compromising the generalizability of trial findings to broader clinical populations. Several solutions are proposed that permit single centers to participate in multiple studies while minimizing or eliminating selection bias, including within-center use of a permuted-block enrollment strategy. The issue of trial allocation among multiple available studies has received insufficient attention from clinical trial designers, epidemiologists, and statisticians. Currently an inescapable problem for clinical stroke investigators, it arises in any clinical medical research field with rapid basic-to-clinical scientific advances.


CONCLUSIONS
It is recommended that centers participating in multiple, concurrent clinical trials (1) use an articulated, formal method of patient allocation that is blinded or indifferent to clinical variables; (2) avoid assignment solely according to time since onset or unique patient criteria; and (3) avoid any influence of belief in agent efficacy on allocation.
Saver
J L
JL
University of California at Los Angeles Neurovascular/Stroke Center, Department of Neurology, USA.
D000208:Acute Disease; D015982:Bias; D002545:Brain Ischemia / Q000628:therapy; D002561:Cerebrovascular Disorders / Q000628:therapy*; D002986:Clinical Trials as Topic; D006782:Hospitals, Special; D006801:Humans; D009042:Motivation; D015337:Multicenter Studies as Topic; D018579:Patient Selection; D011897:Random Allocation; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D013997:Time Factors