title: Can clinical trials requiring frequent participant contact be conducted over the Internet? Results from an online randomized controlled trial evaluating a topical ointment for herpes labialis.
abstract: BACKGROUND
  The Internet has tremendous appeal for conducting randomized clinical trials and may be especially applicable to trials requiring frequent participant contact. Trials of cold sore remedies, for example, often require daily clinic visits during outbreaks, imposing substantial burden on participants. An Internet-based randomized clinical trial design may reduce this burden, permitting frequent symptom reports with considerably less effort.
  
  
  OBJECTIVE
  To evaluate the feasibility of a Web-based randomized clinical trial requiring frequent participant interaction, using a 6-month, double-blind, randomized, placebo-controlled pilot trial of a topical ointment containing dioctyl sodium sulfosuccinate (DSS) (Zilex; Meditech Pharmaceuticals, Inc, Scottsdale, Arizona, USA) intended for treatment of recurrent herpes labialis. A secondary objective was to obtain preliminary data on effectiveness outcomes, to assist in planning a fully-powered trial of DSS.
  
  
  METHODS
  Adults with physician-confirmed herpes labialis were recruited to apply to the trial. Eligible applicants were randomized to DSS or placebo, mailed to them upon enrolment with instructions to apply topically every 2 hours for the duration of every cold sore outbreak. Participants were instructed to complete online questionnaires at 2-week intervals and, at the initiation of a cold sore, daily "outbreak questionnaires" until outbreak termination. Feasibility outcome measures included trial participant characteristics, frequency of cold sores, participant retention and adherence (to study medication), and data completeness. Treatment effectiveness outcome measures included outbreak duration, days to crust formation, and pain.
  
  
  RESULTS
  Of the 292 individuals applying, 182 screened eligible; 32 participants with confirmed herpes labialis enrolled in the trial. 16 were randomized into the verum group and 16 into the placebo group. 29 (91%) participants completed the trial. During the trial, 34 outbreaks were reported among 23 (72%) participants, resulting in a cold sore incidence rate of 19.8 per 100 person-months of observation. Online data were available for 32 outbreaks; the absence of a resolution date made it impossible to accurately calculate the duration of 12 (38%) outbreaks. Although the DSS treatment group had a shorter mean outbreak duration (6.6 vs 7.7 days, P =.2) and fewer mean days to crust formation (3.5 vs 4.9, P =.1), these differences did not reach statistical significance. The DSS group has statistically significant lower mean pain scores (3.1 vs 7.6, P =.04), but participants in this group also consumed more acetaminophen tablets than the placebo group (1.1 versus 0.5, P=.55). Adherence to medication was similar in both groups: 7 (50%) of the verum group reported using the cream as directed compared to 6 (46.2%) in the placebo group; (P =.8).
  
  
  CONCLUSIONS
  We efficiently recruited participants and achieved high overall retention rates. However, participant adherence to the daily outbreak visit schedules was low and only 7 (50%) participants used the cream as directed. These limitations could be addressed in future Internet-based studies by using Personal Digital Assistants (PDAs), using reminder devices, and providing incentives. By enhancing participant adherence, clinical trials requiring frequent participant contact may be feasible over the Internet.
authors.affiliation: Division of Rheumatology, Tufts-New England Medical Center, Box 406, 750 Washington Street, Boston, MA 02111, USA. mformica@tufts-nemc.org
authors.forename: Margaret
authors.initials: M
authors.lastname: Formica
authors.forename: Karim
authors.initials: K
authors.lastname: Kabbara
authors.forename: Rachael
authors.initials: R
authors.lastname: Clark
authors.forename: Tim
authors.initials: T
authors.lastname: McAlindon
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D004143:Dioctyl Sulfosuccinic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006560:Herpes Labialis / Q000188:drug therapy*; D006801:Humans; D020407:Internet / Q000639:trends*; D008297:Male; D008875:Middle Aged; D009824:Ointments / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D010865:Pilot Projects; D016032:Randomized Controlled Trials as Topic / Q000379:methods* / Q000639:trends*; D012651:Self Medication / Q000379:methods; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D009824:Ointments; D004143:Dioctyl Sulfosuccinic Acid