• To evaluate the efficacy of topical acne agents in the treatment of Acne Vulgaris.
• To assess the pooled treatment effect across multiple studies.

• Conduct a thorough literature search to find research that is pertinent.
• Conduct a meta-analysis to compile information from a few chosen papers.

• Controlled clinical trials (CCTs) and randomized controlled trials (RCTs).
• Research contrasting topical acne treatments with a placebo.
• Research involving people who have been diagnosed with Acne Vulgaris.
• Studies reporting treatment effectiveness outcome measures (such as lesion counts, changes in clinical severity, and patient-reported outcomes).

A thorough search of electronic databases (such as PubMed and Embase) was carried out using pertinent keywords and Medical Subject Headings (MeSH) phrases. The search phrases included the following domains: “efficacy”, “therapeutic efficacy”, “topical acne agents”, “topicals”, “Acne Vulgaris”, and “placebo AND topicals”. Accordingly, the Boolean operators “OR” and “AND” were used in this study to join concepts.

The identified studies based on predefined inclusion criteria was screened.

• Using a standardized form, pertinent data from the included studies was retrieved.
• Data on participant demographics, intervention details, outcome measures, and results, as well as study characteristics (such as the author, year, and sample size), were gathered.

The following analysis utilized the R packages meta (Schwarzer 2007) and metasens (Balduzzi et al. 2019):

• Based on the types of reported outcome measures, the pooled effect size using the preferred measure (relative risk) was determined.
• A random effects model was applied to account for any potential study heterogeneity.
• A forest plot was created to show both the overall treatment effect as well as the results of each individual research.
• A funnel plot was used to evaluate publication bias.

• Since this study is a meta-analysis of already published data, ethical review is not necessary. However, ethical standards for conducting and reporting research were upheld.

There were 197 potentially suitable papers found by a systematic literature search (65 from PubMed, 80 from Google Scholar, and 52 from Embase), of which 21 matched the eligibility requirements for the analysis (Fig. 1). Study characteristics are included in Suppl. material 1.

Figure 1. 

Flowchart diagram for selected plots.

According to the findings of this meta-analysis of topical pharmaceutical therapies for Acne Vulgaris, a total of 14 studies (out of 21 without missing values) were analyzed, amounting to a total of 2594 observations (Table 1). There were 601 events in these trials (Table 1), which normally denote the occurrence of an important result or event; in this case, the events in question had to do with the efficacy or reaction of topical therapies for Acne Vulgaris. The meta-analysis can determine the overall treatment impact and evaluate the efficacy of topical pharmacological therapies for Acne Vulgaris by considering the ratio of events to observations. In summary, 14 trials with a combined total of 2594 observations and 601 events make up the meta-analysis of topical pharmacological therapies for Acne Vulgaris. These findings point to a sizable body of data and offer a solid basis for assessing the efficacy of the treatments and making judgments about how well they manage Acne Vulgaris. Topical treatments analyzed in these studies include Salicylic acid, Benzoyl Peroxide, Adapalene, Azelaic acid gel, Fusidic acid lotion, Retinoic Acid, Clindamycin, Isotretinoin gel, Erythromycin gel, Tazarotene gel, Chloroxylenol and Zinc Oxide cream, Tretinoin topical gel, Retinaldehyde/Glycolic acid combination, Triethyl citrate and Ethyl linoleate combination lotion, Zinc acetate, Ketoconazole cream and Superoxidized solution. Their mechanisms of action are described in Suppl. material 1.

The forest plot (Fig. 2) displays the results of a meta-analysis of topical pharmacological treatments for Acne Vulgaris, showing that topical acne agents are preferred to placebo. The results include the relative risk (RR) estimates and their respective 95% confidence intervals (95%-CI) for each study, as well as the percentage weights assigned to each study in both the common effect model (%W(common)) and random effects model (%W(random)).Similar results were found by Eichenfield et al. (2013) and Iraji et al. (2007), with RR estimates of 61.4296 [8.6332; 437.1013] and 13.0000 [1.8130; 93.2178] and all demonstrating a significant decline in acne with topical therapy, respectively.

Figure 2. 

Forest plot showing risk ratio and 95% confidence interval for each study along with study weight.

It is crucial to keep in mind that a few studies, including Barbareschi et al. (1991), Glass et al. (1999), Papageorgiou and Chu (2000), Charakida et al. (2007), Exner et al. (1983), and Chottawornsak et al. (2019), include missing data that is marked as “NA.” These studies might not offer precise RR values; therefore, they can’t be used to assess the overall treatment effect.

The percentage weights allocated to each study are also shown in the forest plot (Fig. 2), indicating their influence on the evaluation of the treatment’s overall effectiveness. The estimated effect is more affected by studies with heavier weights. For instance, Tirado-Sanchez et al. (2013) and Alirezai et al. (2005) have considerably greater weights in both models, indicating that they significantly contributed to the calculation of the overall treatment impact.

The forest plot is consistent with the finding that topical pharmaceutical treatments for Acne Vulgaris are preferred to placebo. Strong support for the efficiency of topical acne medications in treating Acne Vulgaris is shown by the significant RR estimates and the condensed confidence intervals in several of the included trials.

The RR estimate for the common effect model is 5.1986 with a 95% confidence interval of [3.8070; 7.0990] (Fig. 2; Table 2). According to this, persons who receive topical acne treatments have a 5.1986 times higher chance of getting a good result than those who receive a placebo. The RR estimate is statistically different from the null hypothesis that there is no difference between the treatments, according to the z-score of 10.37. Strong evidence is presented against the null hypothesis by the p-value, which is less than 0.0001, which shows a substantial treatment effect in favor of topical acne treatments.

Additionally, a significant treatment impact in favor of topical acne medications is seen in the random effects model (Fig. 2; Table 2). With a 95% confidence interval of [2.5820; 11.1790], the RR estimate is 5.3725. This implies that the treatment impact is of a similar size to the common effect model. The occurrence of a substantial treatment effect is supported by the z-score of 4.50, which shows that the RR estimate significantly differs from the null hypothesis, and the p-value of less than 0.0001.

Whether the common effect model or the random effects model is applied, the forest plot findings consistently show that topical acne treatments are linked with a much higher likelihood of good outcomes compared to placebo. These results offer solid proof of the efficiency of topical pharmaceutical therapies for treating Acne Vulgaris. The plot also offers measures of heterogeneity, which aid in evaluating the degree of variation in the outcomes across the included studies, in addition to treatment effect estimates.

The metrics of heterogeneity presented in the forest plot are tau2, tau, I2, and H, which are quantified as tau2 = 1.2348 [0.4110; 4.0914]; tau = 1.1112 [0.6411; 2.0227]; I2 = 73.3% [54.5%; 84.3%]; and H = 1.93 [1.48; 2.52]. The anticipated amount of variation in treatment effects that goes beyond pure chance is represented by tau2 (Pustejovsky and Tipton 2022). Tau2 is estimated to be 1.2348 in this meta-analysis, with a 95% confidence interval of [0.4110; 4.0914]. Tau is 1.1112 with a 95% confidence interval of [0.6411; 2.0227], where tau is the square root of tau2. These numbers show how heterogeneous the studies’ data are.

I2 describes the percentage of overall treatment effect variance that can be attributed to heterogeneity (Higgins and Thompson 2002). The I2 score in this situation is 73.3%, and the 95% confidence interval is [54.5%; 84.3%]. This shows that there is heterogeneity between the trials which accounts for a sizable portion of the diversity in treatment outcomes. Greater heterogeneity is indicated by higher I2 values.

Another measure of heterogeneity is H, which, according to Mittlböck and Heinzl (2006), is the ratio of overall variability (which includes both within-study and between-study variability) to within-study variability. The H value for this meta-analysis is 1.93, and the 95% confidence interval is [1.48; 2.52]. Significant heterogeneity is indicated by values larger than 1.

The findings show that the papers included in the meta-analysis of topical pharmacological therapies for Acne Vulgaris exhibit moderate to significant heterogeneity. This heterogeneity shows that variables other than pure chance may have an impact on the diversity in treatment outcomes seen across studies. Different study designs, patient demographics, treatment regimens, or outcome measures could all be potential causes of variation (Benjamin et al. 2017).

A test of heterogeneity, which determines if the observed variation in treatment effects across the studies is statistically significant, is shown in the forest plot based on the meta-analysis of topical pharmacological therapies for Acne Vulgaris. A Q value of 48.60 with 13 degrees of freedom and a p-value of less than 0.0001 are reported in this instance by the test of heterogeneity. According to Barili et al. (2018), the Q statistic is a measurement of the overall variability in treatment effects across trials, considering both within-study and between-study variability. The number of independent pieces of information that can be used to estimate the variability is indicated by the degrees of freedom. The Q value of 48.60 in this meta-analysis indicates high heterogeneity among the studies. The statistical significance of the heterogeneity is indicated by the p-value attached to the Q statistics. The p-value in this instance is less than 0.0001, indicating that it is unlikely that the observed heterogeneity could have happened by chance alone.

A test of funnel plot asymmetry using linear regression is included in these results (Fig. 3). This test evaluates the potential for publication bias, which is the selective publication of studies based on their findings (Hunter et al. 2014).

Figure 3. 

Funnel plot assessment of publication bias.

The test’s findings for linear regression are as follows: The corresponding p-value is 0.2196, the degrees of freedom (df) are 12, and the test statistic (t-value) is -1.30. The link between the asymmetry of the funnel plot and the standard error of the treatment effect estimates is measured by the t-value (Stanley 2005). The funnel plot may be asymmetric in this instance, but the negative t-value does not statistically signify this.

Additional details concerning the bias and intercept of the linear regression model are revealed by the sample estimates. The bias estimate is -1.8713, suggesting that there may be a systematic bias in the way that studies are published. The standard error of the bias estimate (se. bias), however, is 1.4449, which suggests that there is some ambiguity surrounding this estimate. The standard error of the intercept (se. intercept) is 0.5538, while the estimated intercept is 2.0444.

Overall, there isn’t much proof of publication bias in the meta-analysis of topical pharmaceutical therapies for Acne Vulgaris, according to the findings of the linear regression test of funnel plot asymmetry.