Feasibility of postponed prescriptions in the Netherlands

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University Medical Center Rotterdam
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Interventions for Molluscum ContagiosumSystemati
c Review
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Background

• Common viral skin infection
• Probably resolves within months without scarring
• Usually treated in primary care
• Many treatments have been promoted
• Absence of clear evidence supporting treatment

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More background

• Caused by virus (Molluscipox)
• Infection follows contact with infected persons
  or contaminated objects
• Single or multiple papules, usually lt 20
• Size may vary from 1 mm to over 10 mm
• Common form mostly found in children
• Other forms sexually transmitted variant and in
  immunocompromised hosts

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Skin diseases in children in general practice
top-5 (incidence / 1000 patient years)
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Many published treatment options for molluscum
contagiosum

• Surgical
• Topical
• Systemic
• Awaiting natural resolution

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• Surgical Cryotherapy, curettage, physical
  expression (squeezing), pulsed dye laser,
  curettage with punch
• Topical Acidified nitrite, Australian lemon
  myrtle oil, cantharidin, cidofovir, imiquimod,
  povidone iodine salicylic acid, phenol,
  podophyllotoxin (HIV patients), potassium
  hydroxide, retinoic acid, salicylic acid,
  milkweed, silver nitrate
• Systemic Aureomycine, cimetidine, Calcarea
  carbonica
• Awaiting natural resolution

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Molluscum Review Team

• Marjolein Berger, GP, PhD
• Chris Butler, GP, professor
• Sanjai Gajadin, medical student
• Sander Koning, GP, PhD
• Jack Menke, GP
• Lisette van Suijlekom-Smit, pediatrician, PhD
• Marjolein Tasche, GP, PhD
• Johannes C van der Wouden, PhD

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Objective

• To assess the effects
• of management strategies (including waiting for
  natural resolution)
• for cutaneous, non-genital molluscum contagiosum
• in otherwise healthy people

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Selection criteria

• RCTs only
• For treatment of molluscum contagiosum
• Excluding trials on sexually transmitted MC
• Excluding trials on MC in people with lowered
  immunity

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Search strategy

• Cochrane Trials Register
• Skin Group Trials Register
• MEDLINE
• EMBASE
• LILACS
• References
• Pharmaceutical companies
• Experts

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Collecting papers and quality assessment

• All in pairs of two reviewers

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Primary outcome measure

• Clinical cure
• (complete disappearance of lesion, as assessed by
  a physician)
• after 1 month

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Secondary outcome measures

• Clinical cure after 3 and 6 months
• Clinical cure at end of study
• Time to cure
• Recurrences
• Adverse effects of treatment
• Spread to other people
• QoL and costs

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Search results

• Cochrane registers 17 hits
• MEDLINE 131 hits
• EMBASE 148 hits
• LILACS 45 hits
• 18 possibly relevant RCT, full text
• 17 further studies through refs and pharma

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35 papers

• Most in english
• French
• Japanese
• Chinese
• Spanish

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5 trials were included

• Antony 2001 (UK)
• Marchanda 1997 (India)
• Ohkuma 1990 (Japan)
• Ormerod 1999 (UK)
• Short 2002 (UK)

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Quote 1

• Question These two papers seem to report on
  partly the same patients. Is that correct?
• Author Although I don't remember well, I think
  the same patients are used in the two articles.

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5 included trialspublication type

• Antony 2001 (conference abstract only)
• Marchanda 1997 (homeopathy journal)
• Ohkuma 1990 (full paper)
• Ormerod 1999 (full paper)
• Short 2002 (abstract unpublished paper)

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5 included trialsinterventions

• Antony 2001 (oral cimetidine vs placebo)
• Marchanda 1997 (homeopathic Calcarea carbonica vs
  placebo)
• Ohkuma 1990 (povidone iodine and salicylic
  plaster, alone and combined)
• Ormerod 1999 (salicylic acid with vs without
  sodium nitrite)
• Short 2002 (potassium hydroxide vs placebo)

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5 included trials number of patients enrolled

• Antony 2001- 38 patients
• Marchanda 1997 14 patients
• Ohkuma 1990 35 patients
• Ormerod 1999 30 patients
• Short 2002 20 patients
• Total 137 patients

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Quote 2

• Question to Chinese interpreter Could you check
  with Dr H whether patients were randomised?
• Answer Dr. H does not know what is
  "randomisation method", she said "we some days
  use method A, other days use method B, and so
  on."

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Methodological quality

• Randomisation (method of generating sequence)
• Method of allocation concealment
• Blinding
• Loss to follow-up

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5 included trials randomisation

• Antony 2001- randomisation in abstract, no
  details
• Marchanda 1997 not in paper, but personal
  communication
• Ohkuma 1990 - not in paper, but personal
  communication
• Ormerod 1999 in paper, group sequential design
• Short 2002 in paper, no details

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5 included trials allocation concealment

• None of the papers provided information

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5 included trials blinding

• Antony 2001- double-blind in abstract
• Marchanda 1997 double-blind, no details
• Ohkuma 1990 - not in paper, probably not blinded
• Ormerod 1999 double-blind, no details
• Short 2002 (UK) double-blind, no details

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Quote 3
Question How many dropouts in each arm of the
study? Answer There were dropouts, but we did
not count them.
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5 included trials loss to follow-up

• Antony 2001- 50 dropouts, for whom no results
• Marchanda 1997 20 dropouts, for whom no
  results
• Ohkuma 1990 no loss reported, all patients in
  outcome table
• Ormerod 1999 30 dropouts at 1 month, ITT
• Short 2002 (UK) 10 dropouts after 2 weeks, ITT

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5 included trials results?

• Given small trials and methodological flaws,
  presenting numerical information not very useful
• Some differences statistically significant
• Huge confidence intervals

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Conclusions of review

• Evidence insufficient to recommend any one
  intervention
• Additional well-designed RCTs needed on common
  treatment options against credible placebo or no
  intervention
• Clinicians should recommend expectant management
  until evidence emerges for safe and effective
  treatment

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• Review published April 2006
• Search finished March 2004
• Any news?

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At least two new studies

• Burke et al (2004), essential oil of Australian
  lemon myrtle vs placebo (n31 children)
• Hanna et al (2006), comparing four treatments-
  curettage- cantharidin- salicylic acid-
  imiquimod (n 124 children)
• Awaiting assessment

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Thanks!

• Adrie Hollestein, Daan Muris, Kazutomo Ohkuma,
  Tony Ormerod, and Hywel Williams for drawing our
  attention to relevant studies.
• Drs. Manchanda, Kazutomo Ohkuma and Tony Ormerod
  kindly provided additional information regarding
  their studies and Kate Short generously sent us
  her full paper before it was submitted for
  publication.
• The editorial base provided help in tracing and
  translating papers.
• We also thank Himiko Luiken for translating the
  unique study on the natural history of molluscum
  by Tsukasa Takemura and colleagues, and Taixiang
  Wu for interviewing Dr He on details of her study
  design. We thank Philippa Middleton, Tina Leonard
  and Hywel Williams for their comments on earlier
  drafts of the review.
• The editorial base would like to thank the
  following people who were external referees for
  this review Anthony Ormerod (content expert),
  and Jack Tweed (consumer).

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GP management