Findings from Meta-Analysis on Imiquimod Treatment for BCC Misleading

Imiquimod 5% cream may be as effective as other treatments for basal cell carcinoma (BCC) according to a meta-analysis data published in the Journal of Dermatology Treatments. However, issues with methodology, data analysis, and interpretation may render the study’s findings unreliable and misleading suggests a critical review of the study.

The original meta-analysis was conducted for the purpose of evaluating the efficacy and safety of treatment with imiquimod vs other treatments in patients with low-risk BCC. The investigators searched databases using the terms, “basal,” “cell,” and “carcinoma” with Boolean operators (and, or) to find relevant articles. The final analysis included 13 randomized, controlled trials (N=4265), although 2 studies were excluded as they did not include preferred outcomes. Main outcome measures were histological and composite clearance rates, success and complete response rates, tumor-free survival, and adverse events. The researchers suggested that findings from the meta-analysis demonstrated beneficial effects for imiquimod, making it a valid first-choice treatment for BCC.

The researchers of the meta-analysis used pooled analyses to compare imiquimod with comparator treatments and stated the percent clearance rate to be 77.26% for imiquimod vs 4.54% for “other treatment groups.” The other treatment groups included combined data from vehicle and active comparators, such as surgery and photodynamic therapy. However, pooling data from vehicle and active comparators was considered clinically inappropriate by authors of a critical review of the study. The study researchers reported that imiquimod had a higher histological clearance rate than both vehicle and cryosurgery. This was deemed implausible by the reviewers because it ignored the fact that topical imiquimod treatments have been shown to not be as effective as excisional surgery. The study also failed to address the question of subtypes of BCC that are suitable for the application of imiquimod cream, the reviewers noted. A clinical consultation would be necessary to properly evaluate individual patients and location of tumors, it was felt.

Multiple issues were raised by the reviewers, who assessed the study using the PICO framework and appraised validity via the PRIMSA checklist. The overall assessment of the study cited issues with study completeness as well as a failure to ask a clinically meaningful question, failure to take similar existing studies into account, several major flaws in methodology, and invalid interpretation of results.

The meta-analysis was based on the 13 randomized controlled trials, which included several duplicate studies as well as double-counting of the same participants at various time intervals (3-year and 5-year respectively). This lead to biased accounting of the follow-up data and conclusions from certain clinical trials. Furthermore, all subtypes of BCC were included, although infiltrative and superficial BCC are different in terms of disease behavior and therapy response, the reviewers pointed out.

In addition, the study did not have a verifiable protocol, which made the purpose of the research unclear, aside from measurement of the six factors associated with BCC. The reviewers pointed out that the study did not specify the rationale for selection of topical imiquimod over other surgical treatments and did not include a description of the frequency of imiquimod regimens applied to patients with different BCC types.

The meta-analysis was scored for quality on the MSTAR 2 checklist and the overall rating in the confidence of the results was “critically low” making the validity of the study questionable at best. Furthermore, the study “should not be relied on to provide an accurate and comprehensive summary of the available studies.”  The reviewers also wrote that the meta-analysis failed to factor in similar reviews, had numerous methodological flaws, and provided an incorrect interpretation of the available data.  

In recent years, there has been an increase in the number of biased and misleading systematic reviews and meta-analyses, the reviewers said. They concluded that journal editors and reviewers must adhere to the PRISMA guidelines to prevent the duplication of existing reviews in dermatology, especially for reviews used to inform clinicians about practices that affect patient care.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

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Reference

Olabi B, Tasker F, Williams HC. ‘Efficacy and safety of imiquimod 5% cream for basal cell carcinoma: a meta-analysis of randomized controlled trial’: a critical appraisal [published online July 11, 2019]. J Dermatolog Treat. doi: 10.1080/09546634.2019.1638883