Review of randomised trials using the post-randomised consent (Zelen's) design

Adamson, Joy; Cockayne, Sarah; Puffer, Suezann; Torgerson, David

doi:10.1016/j.cct.2005.11.003

Cited by 124 publications

(116 citation statements)

References 67 publications

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“…Interestingly, not many trials in biomedicine have applied this design, and the majority of those that have suggest that the reason is to avoid bias due to a Hawthorne effect a distortion of the results caused by the response the participants to the special attention they receive from researchers rather than to improve recruitment. 2 Many, if not most, interventions in restorative dentistry and prosthodontics can be considered as elective. For many potential patients, the most relevant treatment outcomes are previous patients' satisfaction with the treatment and how it may affect their quality of life.…”

Section: Commentarymentioning

confidence: 99%

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Implant retained or conventional dentures, which give more patients satisfaction?

Jokstad

2006

Evid Based Dent

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Design This was a randomised controlled trial (RCT) set in a dental hospital. Intervention The implant group (IG) had two implants placed in the interforaminal region of the lower jaw followed (after healing) by a denture fixed to the implants by a ball attachment mechanism. In the conventional dentures group (CG), dentures were constructed using conventional replacement denture techniques. Patients in the IG had conventional upper dentures made in the same fashion. Outcome measure The performance of the dentures was evaluated using an oral health impact profile (OHIP) and a denture satisfaction scale before treatment and 3 months post-treatment. Results Analysis was conducted on an intention-to-treat basis. Substantial improvements in oral-health-related quality of life and denture satisfaction were reported by both groups. There were, however, no significant differences post-treatment between the groups. Patients randomised to the IG who declined implants had significantly lower pretreatment OHIP scores and there were significantly greater pre-/ post-treatment change-scores for individuals who had implants compared with the change-scores of people who declined. Conclusions There were no significant post-treatment differences between the groups, but a treatment effect may be masked by the intention-to-treat analysis. The pre-/ post-treatment OHIP change-scores were significantly greater for people receiving implants than for those who refused. CommentaryThis very interesting study is the first RCT in dentistry where the post-randomised single-consent design described by Zelen in 1979 1 has been used. The rationale for introducing a study design where the participants are randomised before acquiring consent was that it might enhance patient recruitment to clinical trials. Interestingly, not many trials in biomedicine have applied this design, and the majority of those that have suggest that the reason is to avoid bias due to a Hawthorne effect a distortion of the results caused by the response the participants to the special attention they receive from researchers rather than to improve recruitment. 2

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Section: Commentarymentioning

confidence: 99%

“…This adds to the already controversial ethical dilemmas associated with this study design. 2 Could this high dropout have been predicted? Perhaps not, as a similar occurrence also puzzled the authors of another recent implant trial.…”

Section: Commentarymentioning

confidence: 99%

Implant retained or conventional dentures, which give more patients satisfaction?

Jokstad

2006

Evid Based Dent

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“…Secondly, contamination of the control group, whose members wittingly or unwittingly acquire some of the exposure that should have been restricted only to those in the intervention group, can be a major problem in such trials. This problem, also referred to as 'contamination bias' or 'dilution bias' [27], is largely avoided by offering participants a genuine choice of moving from one group to the other, if they desire to do so.…”

Section: Discussionmentioning

confidence: 99%

“…Analyses based on the 'intention to treat' (ITT) principle, the accepted standard for all RCTs [12,20], cannot resolve this either when treatments have become effectively 'homogenised' [17,19]. Adamson et al [27], who identified 58 trials that had used a Zelen design between 1990 and 2005, found a mean cross-over rate of 13.8%. Even with the single consent design, a cross-over rate of only 10% requires a 20% increase in sample size to maintain power [19].…”

Section: Discussionmentioning

confidence: 99%

“…Even with the single consent design, a cross-over rate of only 10% requires a 20% increase in sample size to maintain power [19]. With a 10% cross-over in the double consent design, sample size needs to increase with 60% in order to achieve the power of a conventional RCT [19,27]. Fortunately, cross-over was a minor issue in our trial, occurring in less than 1% and being unidirectional, only from the control group to the intervention group.…”

Section: Discussionmentioning

confidence: 99%

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Dealing with Missing Outcomes: Lessons from a Randomized Trial of a Prenatal Intervention to Prevent Early Childhood Caries

Plutzer¹,

Mejía²,

Spencer³

et al. 2010

TODENTJ

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Severe early childhood caries (S-ECC) affects 17% of 2-3 year old children in South Australia impacting on their general health and well-being. S-ECC is largely preventable by providing mothers with anticipatory guidance. Randomised controlled trials (RCTs) are the most decisive way to test this, but that approach suffers from near inevitable loss to follow-up that occurs with preventative strategies and distant outcome assessment.We re-examined the results of an RCT to prevent S-ECC using sensitivity analyses and multiple imputation to test different assumptions about violation of random allocation (1%) and major loss to follow-up (32%). Irrespective of any assumptions about missing outcomes, providing expectant mothers with anticipatory guidance during pregnancy and in the child's first year of life, significantly reduced the incidence of S-ECC at 20 months of age. However, the relative risk of S-ECC varied from 0.18 (95% confidence interval (CI): 0.06 -0.52) to 0.70 (95% CI: 0.56 -0.88). Also the 'number needed to treat' (NNT) to prevent one case of S-ECC varied 2.5-fold: from 8 to 20 women given anticipatory guidance. Multiple imputation provided a best estimate of 0.25 (95% CI: 0.11 -0.56) for the relative risk and of 14 (95% CI: 10 -33) for the number needed to treat.Avoiding loss to follow-up is crucial in any RCT, but is difficult with preventative health care strategies. Instead of abandoning randomisation in such circumstances, sensitivity analyses and multiple imputation can consolidate the findings of an RCT and add extra value to the conclusions derived from it.

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