Randomised controlled trial of the treatment of warts in general practice.

* objective(s) / research question(s):
Is treatment with cryotherapy more effective than treatment with salicylic acid and are both therapies more effective than an expectant awaiting policy (natural history)?
Are there subgroups (age, location, number of warts, previous self-treatment), which react differently on therapy?
* study design:
Randomised controlled trial in 32 GP practices
* study population(s)/ datasets:
Patients (all ages) contacting the general practice with warts.
* intervention:
Comparison of cryotherapy (2-week interval), salicylic acid therapy and an expectantly awaiting policy.
* outcome measures:
1) Cure rate (total disappearance observed by a blinded research nurse), 2) number of persisting warts,
subjective hindrance caused by warts and acceptability of therapy as scored by the patient, 3) adverse effects (including new warts) of the three approaches, 4) additional treatment during and after
intervention period (13 weeks). Follow-up moments at 4, 13 and 26 weeks
* power/data analysis:
Because of presumed less adverse effects and logistic and practical advantages salicylic acid is the preferential therapy when the cure rate for cryotherapy is not more than 20% higher than salicylic acid. .
With an alpha of 0.05 and a beta of 0.20 we need 71 patients in each group. When we estimate a loss to follow-up of 20% we need about 250 patients with new warts. With this number we can also detect a
difference of 20% between expectantly the awaiting policy and the active treatments.
* time schedule:
Months 1-6: development patient record form, recruitment of general practitioners and practice
assistants and instruction in uniform application of cryotherapy, instruction for ointment treatment.
Instruction of research nurses on protocol and on assessment of warts. Months 6-18: patient inclusion, intervention, data collection. Months 18-24: data analysis and preparation of scientific reports.

The usual treatment for warts in Dutch general practice is cryotherapy with liquid nitrogen. More than 50% of all warts are treated with cryotherapy alone and in only 14% salicylic acid is used as mono-therapy.
The prestigious Cochrane review concludes that there is an urgent need for high-quality randomised controlled trials on the routine treatments for common warts, particularly cryotherapy. While there is convincing evidence for the efficacy of topical salicylic acid compared to placebo,
high quality studies in which cryotherapy and salicylic acid compared to natural history are still lacking.
According to the Cochrane review the most urgent need is for a trial to compare topical salicylic acid, cryotherapy and placebo. Since the most recent amendment (May 2003) no new studies are published.

Treatment arms
For the treatment with cryotherapy we chose for a high-intensity regimen: a 2-weekly consultation till the
wart has disappeared (until max. 13 weeks), 3 applications of the same wart per session, each application
until a frozen halo appears of 2 mm around it?s base.
For the local treatment with salicylic acid vaseline album (petrolatum) we use a once a day application of
a concentration of 40% for warts on the sole of the feet and on other parts of the skin. We choose for a
concentration of 40% to offer patients a stronger therapy than the over-the-counter therapies (like
Formule-W), which have a concentration of 17%. Covering the skin up with tape will protect the skin
around the wart. Application will be continued till the wart has disappeared (max. until 13 weeks).
Patients who were randomised into the natural history arm will be informed about the high spontaneous
cure rate. We refrained from a placebo-comparison because this insufficiently resembles daily practice.
An expectantly awaiting group will in the intervention period will reliably reflect patient behaviours,
including seeking of additional therapy (ability to maintain the expectantly awaiting policy).