Context Allocation on the basis of randomization rather than patient choice
is the gold standard of unbiased estimates of efficacy in clinical medicine.
However, randomly allocating patients to treatments that do not accord with
their preferences may influence internal and external validity.
Objective To determine whether preferences affect recruitment to trials (external
validity) and outcomes in trials (internal validity)
Data Sources We searched MEDLINE, EMBASE, PsycINFO, CINAHL, AMED, and the Cochrane
Library for articles published between 1966 and September 2004. We also hand-searched
several major medical journals, searched reference lists of relevant articles,
and contacted authors of published preference designs. The 2 themes in the
first filter of the search strategy were preferences and possible determinants of preferences.
Study Selection Comprehensive cohorts and 2-stage trials that measured or recorded patient
or physician preference, included allocation of participants to random and
preference cohorts, and followed up all participants. We excluded trials with
no recording of preference; of decision aids; with measurements of preferences
for economic analyses; in which patients who refused randomization were followed
up without reference to preferences; and of nonclinical populations.
Data Extraction Up to 4 reviewers independently evaluated the articles, and disagreements
were resolved at project steering group meetings. We extracted data on study
design, measurement of preference, recruitment, attrition, and summary data
on the primary outcome(s) at baseline and each follow-up point.
Data Synthesis Of 10 023 citations identified, 170 articles met screening criteria
and 32 (27 comprehensive cohorts and 5 two-stage trials) were determined to
be eligible and were used in the final review. Although treatment preferences
led to a substantial proportion of people refusing randomization, there was
less evidence of bias in the characteristics of individuals agreeing to be
randomized. Differences in outcome across the trials between randomized and
preference groups were generally small, particularly in large trials and after
accounting for baseline measures of outcome. Therefore, there was little evidence
that preferences substantially interfere with the internal validity of randomized
Conclusions Preferences influence whether people participate in randomized trials,
but there is little evidence that they significantly affect validity.