Article

Spontaneous improvement in randomised clinical trials: meta-analysis of three-armed trials comparing no treatment, placebo and active intervention

The Nordic Cochrane Centre, Rigshospitalet, Dept, 3343, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
BMC Medical Research Methodology (Impact Factor: 2.17). 02/2009; 9:1. DOI: 10.1186/1471-2288-9-1
Source: PubMed

ABSTRACT It can be challenging for patients and clinicians to properly interpret a change in the clinical condition after a treatment has been given. It is not known to which extent spontaneous improvement, effect of placebo and effect of active interventions contribute to the observed change from baseline, and we aimed at quantifying these contributions.
Systematic review and meta-analysis, based on a Cochrane review of the effect of placebo interventions for all clinical conditions. We selected all trials that had randomised the patients to three arms: no treatment, placebo and active intervention, and that had used an outcome that was measured on a continuous scale or on a ranking scale. Clinical conditions that had been studied in less than three trials were excluded.
We analysed 37 trials (2900 patients) that covered 8 clinical conditions. The active interventions were psychological in 17 trials, physical in 15 trials, and pharmacological in 5 trials. Overall, across all conditions and interventions, there was a statistically significant change from baseline in all three arms. The standardized mean difference (SMD) for change from baseline was -0.24 (95% confidence interval -0.36 to -0.12) for no treatment, -0.44 (-0.61 to -0.28) for placebo, and -1.01 (-1.16 to -0.86) for active treatment. Thus, on average, the relative contributions of spontaneous improvement and of placebo to that of the active interventions were 24% and 20%, respectively, but with some uncertainty, as indicated by the confidence intervals for the three SMDs. The conditions that had the most pronounced spontaneous improvement were nausea (45%), smoking (40%), depression (35%), phobia (34%) and acute pain (25%).
Spontaneous improvement and effect of placebo contributed importantly to the observed treatment effect in actively treated patients, but the relative importance of these factors differed according to clinical condition and intervention.

0 Followers
 · 
57 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: A great deal of research over the past decade has examined the appropriateness of curriculum-based measurement of oral reading (R-CBM) in universal screening. Multiple researchers have meta-analyzed available correlational evidence, yielding support for the interpretation of R-CBM as an indicator of general reading proficiency. In contrast, researchers have yet to synthesize diagnostic accuracy evidence, which pertains to the defensibility of the use of R-CBM for screening purposes. The overall purpose of this research was to therefore conduct the first meta-analysis of R-CBM diagnostic accuracy research. A systematic search of the literature resulted in the identification of 34 studies, including 20 peer-reviewed articles, 7 dissertations, and 7 technical reports. Bivariate hierarchical linear models yielded generalized estimates of diagnostic accuracy statistics, which predominantly exceeded standards for acceptable universal screener performance. For instance, when predicting criterion outcomes within a school year (≤9months), R-CBM sensitivity ranged between .80 and .83 and specificity ranged between .71 and .73. Multiple moderators of R-CBM diagnostic accuracy were identified, including the (a) R-CBM cut score used to define risk, (b) lag in time between R-CBM and criterion test administration, and (c) percentile rank corresponding to the criterion test cut score through which students were identified as either truly at risk or not at risk. Follow-up analyses revealed substantial variability of extracted cut scores within grade and time of year (i.e., fall, winter, and spring). This result called into question the inflexible application of a single cut score across contexts and suggested the potential necessity of local cut scores. Implications for practices, directions for future research, and limitations are discussed.
    Journal of School Psychology 08/2014; 52(4):377-405. DOI:10.1016/j.jsp.2014.06.002 · 2.24 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Systematic reviews often investigate the effectiveness of interventions for one sex. However, identifying interventions with data presented according to the sex of study participants can be challenging due to suboptimal indexing in bibliographic databases and poor reporting in titles and abstracts. The purposes of this study were to develop a highly sensitive search filter to identify literature relevant to men's health and to assess the performance of a range of sex-specific search terms used individually and in various combinations.
    07/2014; 3(1):78. DOI:10.1186/2046-4053-3-78
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chiropractic care is a complex health intervention composed of both treatment effects and non-specific, or placebo, effects. While doctor-patient interactions are a component of the non-specific effects of chiropractic, these effects are not evaluated in most clinical trials. This study aimed to: 1) develop an instrument to assess practitioner-patient interactions; 2) determine the equivalence of a chiropractor's verbal interactions and treatment delivery for participants allocated to active or sham chiropractic groups; and 3) describe the perceptions of a treatment-masked evaluator and study participants regarding treatment group assignment. We conducted an observational analysis of digital video-recordings derived from study visits conducted during a pilot randomized trial of conservative therapies for temporomandibular pain. A theory-based, iterative process developed the 13-item Chiropractor Interaction and Treatment Equivalence Instrument. A trained evaluator masked to treatment assignment coded video-recordings of clinical encounters between one chiropractor and multiple visits of 26 participants allocated to active or sham chiropractic treatment groups. Non-parametric statistics were calculated. The trial ran from January 2010 to October 2011. We analyzed 111 complete video-recordings (54 active, 57 sham). Chiropractor interactions differed between the treatment groups in 7 categories. Active participants received more interactions with clinical information (8 vs. 4) or explanations (3.5 vs. 1) than sham participants within the therapeutic domain. Active participants received more directions (63 vs. 58) and adjusting instrument thrusts (41.5 vs. 23) in the procedural domain and more optimistic (2.5 vs. 0) or neutral (7.5 vs. 5) outcome statements in the treatment effectiveness domain. Active participants recorded longer visit durations (13.5 vs. 10 minutes). The evaluator correctly identified 61% of active care video-recordings as active treatments but categorized only 31% of the sham treatments correctly. Following the first treatment, 82% of active and 11% of sham participants correctly identified their treatment group. At 2-months, 93% of active and 42% of sham participants correctly identified their group assignment. Our findings show the feasibility of evaluating doctor-patient interactions in chiropractic clinical trials using video-recordings and standardized instrumentation. Clinical trial design and clinician training protocols should improve and assess the equivalence of doctor-patient interactions between treatment groups. This trial was registered in ClinicalTrials.gov as NCT01021306 on 24 November 2009.
    12/2014; 22(1):42. DOI:10.1186/s12998-014-0042-7

Full-text (2 Sources)

Download
12 Downloads
Available from
Jun 4, 2014