Contamination in trials of educational interventions.

OBJECTIVES: To consider the effects of contamination on the magnitude and statistical significance (or precision) of the estimated effect of an educational intervention, to investigate the mechanisms of contamination, and to consider how contamination can be avoided. DATA SOURCES: Major electronic databases were searched up to May 2005. METHODS: An exploratory literature search was conducted. The results of trials included in previous relevant systematic reviews were then analysed to see whether studies that avoided contamination resulted in larger effect estimates than those that did not. Experts' opinions were elicited about factors more or less likely to lead to contamination. We simulated contamination processes to compare contamination biases between cluster and individually randomised trials. Statistical adjustment was made for contamination using Complier Average Causal Effect analytic methods, using published and simulated data. The bias and power of cluster and individually randomised trials were compared, as were Complier Average Causal Effect, intention-to-treat and per protocol methods of analysis. RESULTS: Few relevant studies quantified contamination. Experts largely agreed on where contamination was more or less likely. Simulation of contamination processes showed that, with various combinations of timing, intensity and baseline dependence of contamination, cluster randomised trials might produce biases greater than or similar to those of individually randomised trials. Complier Average Causal Effect analyses produced results that were less biased than intention-to-treat or per protocol analyses. They also showed that individually randomised trials would in most situations be more powerful than cluster randomised trials despite contamination. CONCLUSIONS: The probability, nature and process of contamination should be considered when designing and analysing controlled trials of educational interventions in health. Cluster randomisation may or may not be appropriate and should not be uncritically assumed always to be a solution. Complier Average Causal Effect models are an appropriate way to adjust for contamination if it can be measured. When conducting such trials in future, it is a priority to report the extent, nature and effects of contamination.

To freeze or not to freeze: a cost-effectiveness analysis of wart treatment.

BACKGROUND: Several general practitioner (GP)-prescribed and over-the-counter therapies for warts and verrucae are available. However, the cost-effectiveness of these treatments is unknown. OBJECTIVES: To compare the cost-effectiveness of different treatments for cutaneous warts. METHODS: We designed a decision-analytic Markov simulation model based on systematic review evidence to estimate the cost-effectiveness of various treatments. The outcome measures studied are percentage of patients cured, cost of treatment and incremental cost-effectiveness ratio for each treatment, compared with no treatment, after 18 weeks. RESULTS: Duct tape was most cost-effective but published evidence of its effectiveness is sparse. Salicylic acid was the most cost-effective over-the-counter treatment commonly used. Cryotherapy administered by a GP was less cost-effective than GP-prescribed salicylic acid and less cost-effective than cryotherapy administered by a nurse. CONCLUSIONS: Duct tape could be adopted as the primary treatment for cutaneous warts if its effectiveness is verified by further rigorous trials. Nurse-administered cryotherapy is likely to be more cost-effective than GP-administered cryotherapy.

Effectiveness and cost-effectiveness of salicylic acid and cryotherapy for cutaneous warts. An economic decision model.

OBJECTIVES: To estimate the costs of commonly used treatments for cutaneous warts, as well as their health benefits and risk. To create an economic decision model to evaluate the cost-effectiveness of these treatments, and, as a result, assess whether a randomised controlled trial (RCT) would be feasible and cost-effective. DATA SOURCES: Focus groups, structured interviews and observation of practice. Postal survey sent to 723 patients. A recently updated Cochrane systematic review and published cost and prescribing data. REVIEW METHODS: Primary and secondary data collection methods were used to inform the development of an economic decision model. Data from the postal survey provided estimates of the effectiveness of wart treatments in a primary care setting. These estimates were compared with outcomes reported in the Cochrane review of wart treatment, which were largely obtained from RCTs conducted in secondary care. A decision model was developed including a variety of over-the-counter (OTC) and GP-prescribed treatments. The model simulated 10,000 patients and adopted a societal perspective. RESULTS: OTC treatments were used by a substantial number of patients (57%) before attending the GP surgery. By far the most commonly used OTC preparation was salicylic acid (SA). The results of the economic model suggested that of the treatments prescribed by a GP, the most cost-effective treatment was SA, with an incremental cost-effectiveness ratio (ICER) of 2.20 pound/% cured. The ICERs for cryotherapy varied widely (from 1.95 to 7.06 pound/% cured) depending on the frequency of applications and the mode of delivery. The most cost-effective mode of delivery was through nurse-led cryotherapy clinics (ICER = 1.95 pound/% cured) and this could be a cost-effective alternative to GP-prescribed SA. Overall, the OTC therapies were the most cost-effective treatment options. ICERs ranged from 0.22 pound/% cured for OTC duct tape and 0.76 pound/% cured for OTC cryotherapy to 1.12 pound/% cured for OTC SA. However, evidence in support of OTC duct tape and OTC cryotherapy is very limited. Side-effects were commonly reported for both SA and cryotherapy, particularly a burning sensation, pain and blistering. CONCLUSIONS: Cryotherapy delivered by a doctor is an expensive option for the treatment of warts in primary care. Alternative options such as GP-prescribed SA and nurse-led cryotherapy clinics provide more cost-effective alternatives, but are still expensive compared with self-treatment. Given the minor nature of most cutaneous warts, coupled with the fact that the majority spontaneously resolve in time, it may be concluded that a shift towards self-treatment is warranted. Although both duct tape and OTC cryotherapy appear promising new self-treatment options from both a cost and an effectiveness perspective, more research is required to confirm the efficacy of these two methods of wart treatment. If these treatments are shown to be as cost-effective as or more cost-effective than conventional treatments, then a shift in service delivery away from primary care towards more OTC treatment is likely. A public awareness campaign would be useful to educate patients about the self-limiting nature of warts and the possible alternative OTC treatment options available. Two future RCTs are recommended for consideration: a trial of SA compared with nurse-led cryotherapy in primary care, and a trial of home treatments. Greater understanding of the efficacy of these home treatments will give doctors a wider choice of treatment options, and may help to reduce the overall demand for cryotherapy in primary care.