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Continuous alternate day vs intermittent daily fixed doses of oral isotretinoin in grade 2 acne vulgaris
For correspondence: Dr Shikha Verma, Department of Dermatology, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences, Shillong 793 018, Meghalaya, India e-mail: shikha.b.thakur@gmail.com
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Received: ,
Accepted: ,
How to cite this article: Bikash C, Verma S, Marak A. Continuous alternate day vs intermittent daily fixed doses of oral isotretinoin in grade 2 acne vulgaris. Indian J Med Res. doi: 10.25259/IJMR_2458_2025
Abstract
Background and objectives
The alternate day and the intermittent regimens of isotretinoin are efficacious in treating moderate acne vulgaris with low cumulative doses. The former regimen has been found to be superior in comparative studies using weight-based dosing. The fixed dosing of the two regimens has not been explored in a head-to-head trial. The objective was to compare the efficacy and safety of these regimens at fixed dosages in treating grade 2 facial acne vulgaris.
Methods
It was a randomised, single-blinded, non-inferiority trial. Sixty patients aged 18 years and above with grade 2 facial acne were randomised into two groups: Group A received 20 mg isotretinoin on alternate days, and Group B received 30 mg daily for one week per month for four months.
Results
The mean acne load in group A and B reduced to 5.63±4.87 and 5.63±4.87 from 22.60±10 and 28.70±18.10, respectively. The percentage of participants achieving a significant response was 96.7% and 93.3% in group A and B (P=0.28). The estimates were within the non-inferiority margins. The acne load progressively decreased with greater effect size as the treatment continued. Relapse to pretreatment score was not detected. Side effects were comparable between the groups. The cost was significantly higher with the alternate regimen.
Interpretation and conclusions
The daily intermittent regimen is non-inferior to alternate day regimen at fixed dosages in significantly improving grade 2 facial acne vulgaris with similar side effect profiles. The daily intermittent regimen, also with a lower cost, is thus preferrable.
Keywords
Acne vulgaris
Alternate dose
Cheilitis
Intermittent dose
Isotretinoin
Oral isotretinoin is conventionally used for severe nodulocystic acne and is associated with several side effects including cheilitis, xerosis, epistaxis and increases in aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholesterol and triglyceride levels.1,2 It is increasingly being used for lower grades of acne as treating acne effectively at an early stage is pivotal in preventing permanent scarring.3-6 Various low dose regimens such as daily low dose, intermittent therapy, alternate day therapy or gradually increasing daily dose have been utilised effectively in treating mild to moderate acne vulgaris with comparable efficacy and relapse rate to standard dosing with similar treatment durations.7 These lower dosages are preferred as they reduce the occurrence and severity of adverse effects.8-11 Prevention of relapse is a usual concern before using these regimens in severe acne due to their lower cumulative doses.12 However, even the lower dosages provide similar relapse rate to standard regimen, with lower cumulative dosages in milder acne.7
In view of drug accumulation, sebum suppression and cytokine modulation that corroborates with maintained efficacy of isotretinoin, these low dose regimens are expected to provide similar results.13,14 However, the reviewed evidence revealed differences in efficacy and relapse rate among these modified regimens. The continuous low dose regimen has been reported to be the most effective especially in terms of relapse as the low cumulative dosage regimens (<120 mg/kg) provide lesser relapse rate with increase in cumulative dosage.15
Considering lower treatment costs, lesser reported side effects and similar reduction of acne load compared to continuous low dose treatment, the alternate day and intermittent regimens (one week per month) were included in our study.16-19 Some studies have directly compared alternate day with intermittent regimen using the same weight based dosing and revealed alternate day regimen to be superior in reducing acne with similar incidence of side effects.10,20 The lower dose and number of treated days probably contributed to lower efficacy with the intermittent regimen. Foreseeing a lower treatment cost and therefore an extendable course with intermittent regimen compared to alternate day dosing, we wanted to prove its non-inferiority.21 The dosages were fixed in our study to provide uniformity and ease in prescribing. Moreover, isotretinoin capsules are mostly available as 10, 20 or 30 milligrams and a dosage calculated by weight often gets rounded off to the nearest available milligrams while prescribing. Thus, a non-inferiority trial was conducted to compare the efficacy, safety and cost of fixed alternate day regimen with fixed intermittent regimen of isotretinoin.
Methods
This study was conducted by the department of Dermatology, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences, Shillong, Meghalaya, a tertiary centre in Northeast India and completed within a period of 12 months (October 2023 to September 2024). It was a single blinded, randomised non-inferiority trial registered prospectively under Clinical Trials Registry India (CTRI/2023/09/057402) and was approved by the Institute Ethics Committee of the institute. The procedures followed were in accordance with the ICMR’s Ethical guidelines for Biomedical Research on Human Participants (2017).
The alternate day dose was fixed at 20 mg based on its previous efficacy in moderate acne.18,22 Considering the reference average weight of an Indian adult as 60 kg (65 kg for male and 55 kg for female), the intermittent dose was fixed at 30 mg (0.5mg/kg/day- lowest effective dose).3,14,22,23
Non inferiority margin (d)
The efficacy of fixed alternate day regimen in terms of percentage of successful treatment and effect size for improvement of mean acne load were taken as 87.5% and 2.28 (90% confidence interval: 1.99-2.55) respectively.18,22 The non inferiority margin was calculated such that the alternate regimen may be better than intermittent regimen but not by more than a difference of 25 %. Thus, the final non inferiority margin was established as 22 % (0.25 X 87.5) and 0.49 (0.25 X 1.99) for the two primary outcome measures.24
Sample size
Taking the percentage of successful treatment with alternate day and intermittent dosing of isotretinoin as 87.5% and 88% respectively, power as 80%, alpha error as 5%, with 90% two-sided confidence interval and non-inferiority margin (d) of 22%, the sample size was calculated as 54 (23 in each group).18,19,25 With an anticipated loss to follow up of 10%, the sample size was increased to 30 per group.
Sampling method
Patients aged 18 years and above diagnosed with grade 2 facial acne vulgaris constituted the study population. All those who were isotretinoin naive irrespective of whether they were on/off topical therapies or oral antibiotics at the time of recruitment were included. A washout period of 4 weeks was given before initiating isotretinoin. The exclusion criteria included pregnant /lactating women, women planning for conception, polycystic ovarian syndrome (PCOS) or hyperandrogenism, deranged liver function or lipid profile. Written consent was taken and a structured proforma was used for recording data. Female participants were explained about the teratogenicity of isotretinoin and avoidance of conception till 1 month after treatment. The patients were also advised to refrain from donating blood for one month post isotretinoin use.
Randomisation
The study participants were randomised into two groups as Group A: Alternate day (20 mg) isotretinoin for 4 months and Group B: Intermittent dose (30 mg daily for one continuous week per month) isotretinoin for 4 months. Block randomisation of varying block sizes was done with an allocation ratio of 1:1. The random sequence was concealed before allocation by SNOSE technique (Serially Numbered Opaque Sealed Envelope). The first author randomised the participants to their respective treatment groups. The person (second or third author) assessing the change in total acne load and side effects was blinded.
Assessment
Grading of acne vulgaris was done as: Grade 1 (mild): Comedones, occasional papules, Grade 2 (moderate): Papules, comedones, few pustules, Grade 3 (moderate): Predominant pustules, nodules, abscesses and Grade 4 (severe): Mainly cysts, abscesses, widespread scarring.26 Total acne load (TAL) was calculated using the definition severity index (Supplementary Material).27 Pre-treatment TAL was determined on the day of starting treatment. Patients were advised to set alarms/reminders on their mobile phones or mark their calendars with respect to the days on which isotretinoin was to be taken. The patients were followed up every month for 4 months and at 4 months post treatment. Reminder texts/calls were used to ensure monthly follow ups. The participants were also asked to bring back the empty medicine packets during their follow-ups. The participants were not prescribed any active anti-acne agents during the 4 months post treatment. A ‘clinically significant response/successful treatment’ was declared when there was a decrease in acne load by >50 % at the end of 4 months.18 Relapse was defined as the increase in acne severity to pretreatment level after termination of therapy. The liver function test (aspartate transaminase, alanine tramsaminase, gamma glutamyl transferase, alkaline phosphatase, albumin, globulin, total, direct and indirect bilirubin) and fasting lipid profile were checked at baseline, 2 months and 4 months. Urine pregnancy test was done for all females and hormonal profiles (free/total testosterone, dehydroepiandrosterone sulphate, 17-hydroxy progesterone, follicle stimulating hormone/luteinising hormone) with transvaginal/transabdominal ultrasonography was advised to rule out PCOS or other common causes of hyperandrogenism.28,29
Discontinuation criteria
We decided to discontinue the respective treatment regimen if any of the following parameters were met: Serum alanine transaminase >36 IU/L, serum aspartate transaminase >30 IU/L, serum cholesterol >300 mg/dL and serum triglycerides > 400 mg/dL. Patients who did not achieve treatment success at the end of 4 months were switched to the conventional daily isotretinoin (0.5 mg/kg/day).
Outcome measures
The primary outcome measures included (i) the difference in mean total acne load between the two regimens and (ii) the difference in percentage of participants from the alternate and intermittent regimens achieving clinically significant response.
The secondary outcome measures included (i) improvement in total acne load with the two regimens throughout the follow up period including relapse rate; (ii) difference in percentage of participants experiencing side effects; and (iii) cost of isotretinoin between the two groups.
Statistical analysis
Data were analysed using Jamovi software (version 2.6).30 Categorical variables were presented as frequency/percentages and continuous variables as mean with standard deviation. The efficacy of the regimens and the difference in efficacy between the two groups were analysed with both per protocol (PP) and intention to treat (ITT) analysis. For ITT analysis, missing values were imputed with the mean of the available data. Friedman test and post hoc analysis (Durbin Conover) were used to compare among the monthly TAL in the same group. For difference in TAL between groups, effect size was calculated as Cliff’s delta with P values derived from Mann-Whitney U test.31 Unpaired t test was utilised to determine any difference in mean age and weight between the two groups. Chi square test was used to determine the differences in patient characteristics, percentages of successful treatment, side effects and patient satisfaction. A P value of <0.05 was considered statistically significant. For post hoc analysis, Bonferroni correction was used to adjust the significant value of P to 0.003 (0.05/15).
Results
Sixty participants (30 in each group) were recruited ( Figure). One patient and two patients from Group A and Group B respectively did not achieve clinically significant response. The mean age was similar across groups (Group A: 21.9±2.70; Group B: 22.5±2.35), with no statistically significant difference. Group A had a male-to-female ratio of 1.09:1, while Group B showed a higher male predominance (2.83:1). Group A had a lower mean weight (53.5±4.14 kg) compared to Group B (55.7±3.38 kg), with no statistically significant difference (P=0.05). Both groups predominantly consisted of individuals with oily skin (95.7%), and only a small proportion had combination skin (4.3%). Pre-treatment liver function tests and lipid profiles were within normal limits in all participants in both groups. The cumulative isotretinoin dose in Group A and B was 1200 mg (60 capsules) and 840 mg (28 capsules), respectively.
The mean weight-based dose of intermittent regimen was 0.50 (range: 0.47 to 0.55; coefficient of variation (SD/mean): 4%; variance: 0.0006). The measures for the alternate regimen were: mean: 0.33; range: 0.30 to 0.37; coefficient of variation (SD/mean): 5%; variance: 0.0004. There was no significant difference in the effectiveness of each regimen between participants weighing >60 kg and those <60 kg.
The effect size for the difference in acne load between the groups was small across the follow up assessments with similar values in both ITT and PP analysis ( Table I). At the end of 4 months, the upper CI of the effect size in ITT and PP analysis were within the non-inferiority margin of 0.49. Likewise, the difference in percentage of participants achieving clinically significant response was similar in both analyses ( Table II). The lower limit of the CI for this outcome was also below the non-inferiority margin of –22 %.
| Analysis (sample size in group A/B) | Group A (Total acne load) | Group B (Total acne load) | P value for difference between A and B | Effect size as Cliff”s delta with 90% confidence interval (Group B-Group A) | |||||
|---|---|---|---|---|---|---|---|---|---|
| Mean±SD | Median | Range | Mean±SD | Median | Range | ||||
| Baseline | PP (30/30) | 22.60 ± 10.40 | 21.3 | 8-63 | 28.70 ± 18.10 | 21.5 | 14.5-89 | 0.16 | 0.21 (-0.07 to 0.39) |
| ITT (30/30) | 22.60 ± 10.40 | 21.3 | 8-63 | 28.70 ± 18.10 | 21.5 | 14.5-89 | 0.16 | 0.21 (-0.07 to 0.39) | |
| Month 1 | PP (29/29) | 18.00 ± 7.54 | 17.0 | 6.5-40.5 | 23.30 ± 14.80 | 20 | 11-72 | 0.14 | 0.22 (-0.07 to 0.40) |
| ITT (30/30) | 18.00 ± 7.41 | 17.5 | 6.5-40.5 | 23.30 ± 14.50 | 20 | 11-72 | 0.11 | 0.24 (-0.04 to 0.41) | |
| Month 2 | PP (25/24) | 13.70 ± 7.35 | 13.0 | 4-37 | 17.50 ± 12.00 | 14 | 6.5-53 | 0.27 | 0.20 (-0.11 to 0.41) |
| ITT (30/30) | 13.70 ± 6.69 | 13.7 | 4-37 | 17.50 ± 10.70 | 17.5 | 6.5-53 | 0.64 | 0.28 (-0.01 to 0.43) | |
| Month 3 | PP (23/23) | 7.98 ± 5.89 | 7 | 1.5-23 | 9.87 ± 7.53 | 8 | 1.5-29 | 0.42 | 0.14 (-0.16 to 0.37) |
| ITT (30/30) | 7.98 ± 5.13 | 7.98 | 1.5-23 | 9.87 ± 6.56 | 9.87 | 1.5-29 | 0.22 | 0.18 (-0.09 to 0.37) | |
| Month 4 | PP (23/23) | 5.63 ± 5.59 | 4 | 0-22 | 6.26 ± 6.82 | 4 | 0-25 | 0.73 | 0.01 (-0.23 to 0.24) |
| ITT (30/30) | 5.63 ± 4.87 | 5.63 | 0-22 | 5.63 ± 4.87 | 6.13 | 0-25 | 0.36 | 0.12 (-0.14 to 0.33) | |
| Month 8 | PP (21/22) | 4.93 ± 5.47 | 4 | 0-20 | 6.18 ± 5.98 | 4.5 | 0-22 | 0.32 | 0.16 (-0.18 to 0.40) |
| ITT (30/30) | 4.93 ± 4.54 | 4.93 | 0-20 | 6.18 ± 5.08 | 6.18 | 0-22 | 0.12 | 0.23 (-0.05 to 0.41) | |
P values from Mann-Whitney U test. SD, standard deviation; ITT, intention to treat; PP, per protocol
| Analysis (sample size in group A/B) | Group A (>50% improvement); % | Group B (>50% improvement); % | P value for difference between A and B | Difference in percentages of successful treatment with 90% confidence interval (Group B-Group A); % | |
|---|---|---|---|---|---|
| Month 1 | PP (29/29) | 0 | 0 | - | |
| ITT (30/30) | 0 | 0 | - | - | |
| Month 2 | PP (25/24) | 20 | 25 | 0.39 | 5 (-5.43 to 13.77) |
| ITT (30/30) | 16.66 | 20 | 0.54 | 3.30 (-6.05 to 11.70) | |
| Month 3 | PP (23/23) | 95.64 | 91.29 | 0.21 | -4.35 (-9.29 to 2.05) |
| ITT (30/30) | 93.32 | 90 | 0.39 | -3.32 (-9.13 to 3.59) | |
| Month 4 | PP (23/23) | 95.64 | 91.28 | 0.21 | -4.36 (-9.29 to 2.05) |
| ITT (30/30) | 96.66 | 93.33 | 0.28 | -3.33 (-7.76 to 2.24) | |
| Month 8 | PP (21/22) | 100 | 100 | - | - |
| ITT (30/30) | 100 | 100 | - | - |
P values from Chi Square test. Here, ‘-’ represents equal values between A and B
The improvement in acne severity from baseline was statistically significant after the first month of treatment in both groups. This improvement continued with greater effect size in both groups as the months progressed as shown in Supplementary Material. After the treatment period, the TAL continued to decrease but with smaller effect size and non-significant P value. There was no relapse in both groups. The mean percentage improvement of acne severity in Group A and B was 78.9±13.6% and 81.6±15.0%, respectively with no significant difference (P=0.52). Complete resolution was observed in 2 and 4 patients of group A and B respectively (P=0.38).
The most common side effect was general dryness of skin, affecting 78.3% (18) and 82.6% (19) of participants in Group A and Group B, respectively. Dry lips were experienced by 65.2% (15) in Group A and 60.9% (14) in Group B. Dry mouth was reported by one participant of Group B. Facial erythema occurred in 4.3% (1) in Group A and 8.6% (2) in Group B. There were no statistically significant differences. The liver function tests and lipid profiles remained within normal limits.
The participants were well motivated and remained compliant. The average cost of treatment was ₹ 1152±249 and ₹ 689±178 in Group A and B, respectively (P<0.001).
Discussion
Our study revealed a significant response in 95.6% participants with four months of fixed alternate day treatment. In two studies from India, 87.54% and 93.96% of participants respectively achieved clinically significant improvement after 6 months of fixed-dose isotretinoin (20 mg) administered on alternate days, combined with topical 1% clindamycin gel.19,24 Two studies, with their 6 months, intermittent course of isotretinoin at 0.5 to 0.75 mg/kg/day reported significant response in 82.9% and 88% of participants which were close to the result from our study (91.2%).18,19 The higher improvements in our study may be a result of including only moderate acne patients as compared to the previous studies that included patients with higher acne severity.
The present study demonstrated non-inferiority of fixed intermittent regimen to alternate day regimen in moderate acne. The intermittent regimen was compared to the alternate day regimen at the same dosage of 1 mg/kg/day in two randomised studies (moderate to severe acne).10,20 The alternate group performed significantly better than the intermittent group after three months of treatment.
We found no significant difference in the incidence of side effects between the two regimens similar to the study by Agarwal et al10 Previous studies have reported cheilitis (91-100%) followed by xerosis (10.3-17%) as the most encountered side effects in both alternate day and intermittent regimens whereas in our study, the most common was xerosis followed by cheilitis.6,17,19,22
The sustained efficacy of both regimens in our study without relapse can be attributed to the post treatment residual effect, inclusion criteria, good compliance and limited follow up in our study. Agarwal et al10 reported no relapse in both groups like the present study.10 Relapse to pretreatment level was 16.39% (alternate day) and 39% (intermittent) in other studies due to inclusion of truncal acne cases and females with PCOS in their studies along with a longer follow up.18,19
We acknowledge the inherent disadvantage of using fixed dose i.e. overdosing and underdosing. Another limitation is the study being single centric. Long term relapse rate could not be determined due to the limited follow up and the small sample size did not provide adequate power for this aspect. A specific cohort of patients was used and therefore the generalisability of our findings may be limited. Subgroup analysis in terms of age or gender was not performed. Transabdominal ultrasound may not be able to completely rule out PCOS and serum AMH (anti mullerian hormone) was not utilised. The isotretinoin dosages were not correlated with serum isotretinoin or cytokine levels.
Using an appropriate dosage in the right cohort of patients can lead to a significant response as demonstrated in our study. Low dose treatments may be maintained for a longer period or reintroduced with lesser cost, increased willingness to extend therapy and decreased burden of side effects. The intermittent dosing of 30 mg is non inferior to the alternate day dosing of 20 mg isotretinoin in significantly decreasing acne load of grade 2 facial acne patients without underlying hormonal imbalances. The intermittent dosing may be preferred as the cost is lesser with a similar side effect profile.
The various low dose regimens seem equivalent in terms of short-term efficacy as suggested by the post treatment persistence of isotretinoin, effect on sebum and cytokines. Therefore, relapse rates are probably more appropriate for comparing these regimens. Thus, future studies can be conducted with longer follow-up and larger sample sizes to compare the relapse rates of the two regimens.
Author contributions
CB: Conception, design, analysis and interpretation of data; SV: intellectual content, manuscript writing; AM: Manuscript writing. All authors have read and approve the final printed version of the mansucript.
Financial support and sponsorship
None
Conflicts of Interest
None.
Use of Artificial Intelligence (AI)-Assisted Technology for manuscript preparation
The authors confirm that there was no use of AI-assisted technology for assisting in the writing of the manuscript and no images were manipulated using AI.
References
- The use of isotretinoin in acne. Dermatoendocrinol.. 2009;1:162-9.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Uses and complications of isotretinoin therapy. J Am Acad Dermatol.. 2001;45:S150-7.
- [CrossRef] [PubMed] [Google Scholar]
- Effectiveness of conventional, low-dose and intermittent oral isotretinoin in the treatment of acne: A randomized, controlled comparative study. Br J Dermatol.. 2011;164:1369-75.
- [CrossRef] [PubMed] [Google Scholar]
- Low-dose isotretinoin in the treatment of acne vulgaris. J Am Acad Dermatol.. 2006;54:644-6.
- [CrossRef] [PubMed] [Google Scholar]
- Comparison of efficacy of fixed low-dose regimens (daily vs alternate day) of oral isotretinoin in mild to moderate acne vulgaris. J Pak Assoc Dermatol.. 2016;25:291-7.
- [Google Scholar]
- Comparison of the efficacies of intermittent and continuous low-dose isotretinoin regimens in the treatment of moderate acne vulgaris. Int J Dermatol.. 2013;52:1265-7.
- [CrossRef] [PubMed] [Google Scholar]
- Efficacy of low-dose isotretinoin in acne vulgaris. Indian J Dermatol Venereol Leprol.. 2010;76:7-13.
- [CrossRef] [PubMed] [Google Scholar]
- Treatment of acne with intermittent and conventional isotretinoin: A randomized, controlled multicenter study. Arch Dermatol Res.. 2007;299:467-73.
- [CrossRef] [PubMed] [Google Scholar]
- A systematic review of isotretinoin dosing in acne vulgaris. JEADV Clinical Practice.. 2023;2:432-49.
- [Google Scholar]
- Oral isotretinoin in different dose regimens for acne vulgaris: A randomized comparative trial. Indian J Dermatol Venereol Leprol.. 2011;77:688-94.
- [CrossRef] [PubMed] [Google Scholar]
- Comparison of efficacy of fixed low-dose regimens (daily vs alternate day) of oral isotretinoin in mild to moderate acne vulgaris. J Pak Assoc Dermatol.. 2016;25:291-7.
- [Google Scholar]
- The use of isotretinoin in the treatment of acne vulgaris: Clinical considerations and future directions. J Clin Aesthet Dermatol.. 2014;7:S3-S21.
- [PubMed] [PubMed Central] [Google Scholar]
- The use of isotretinoin in low doses and unconventional treatment regimens in different types of acne: A literature review. Postepy Dermatol Alergol.. 2017;34:1-5.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Levels of several inflammatory cytokines in acne patients before and after isotretinoin therapy: A randomized, controlled clinical trial. J Dermatolog Treat.. 2025;36:2540594.
- [CrossRef] [PubMed] [Google Scholar]
- Acne relapse and isotretinoin retrial in patients with acne. JAMA Dermatol.. 2025;161:367-74.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Evaluation of the efficacy and relapse rates of treatment protocols for moderate acne using isotretinoin based on the global acne grading system: Randomized, controlled, comparative study. Dermatol Ther.. 2022;35:e15974.
- [CrossRef] [PubMed] [Google Scholar]
- The effectiveness of intermittent isotretinoin treatment in mild or moderate acne. J Eur Acad Dermatol Venereol.. 2006;20:1256-60.
- [CrossRef] [PubMed] [Google Scholar]
- Efficacy of fixed low-dose isotretinoin (20 mg, alternate days) with topical clindamycin gel in moderately severe acne vulgaris. J Eur Acad Dermatol Venereol.. 2009;23:556-60.
- [CrossRef] [PubMed] [Google Scholar]
- Oral isotretinoin and its uses in dermatology: A review. Drug Des Devel Ther.. 2023;17:2573-91.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Efficacy of low dose oral isotretinoin on alternate day Vs pulses regimen for acne vulgaris treatment: RCT. PJMHS.. 2022;16:116-7.
- [CrossRef] [Google Scholar]
- Through the looking glass: Understanding non-inferiority. Trials.. 2011;12:106.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- A randomized comparative trial of two low-dose oral isotretinoin regimens in moderate to severe acne vulgaris. Indian Dermatol Online J.. 2016;7:378-85.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- ICMR-National Institute of Nutrition. Department of Health Research, Ministry of Health and Family Welfare, Government of India. Short report of nutrient requirement for Indians, Recommended Dietary Allowances (RDA) and Estimated Average Requirements (EAR) - 2020. Available from: https://drklbcollege.ac.in/wp-content/uploads/2020/03/DOC-20220614-WA0002_-1.pdf. accessed on December 21, 2025.
- Defining the noninferiority margin and analysing noninferiority: An overview. Br J Clin Pharmacol.. 2017;83:1636-42.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Sealed Envelope Ltd. 2012. Power (sample size) calculators. Available from: https://www.sealedenvelope.com/power/binary-noninferior/, accessed on December 21, 2025
- Scoring systems in acne vulgaris. Indian J Dermatol Venereol Leprol.. 2009;75:323-26.
- [CrossRef] [PubMed] [Google Scholar]
- A comprehensive critique and review of published measures of acne severity. J Clin Aesthet Dermatol.. 2016;9:40-52.
- [PubMed] [PubMed Central] [Google Scholar]
- A study comparing the clinical and hormonal profile of late onset and persistent acne in adult females. Int J Dermatol.. 2020;59:428-33.
- [CrossRef] [PubMed] [Google Scholar]
- A prospective study of anti-mullerian hormone and other ovarian and adrenal hormones in adult female acne. Dermatol Ther.. 2020;33:e13974.
- [CrossRef] [PubMed] [Google Scholar]
- The Jamovi Project (2024). jamovi. (Version 2.6) [Computer Software]. Available from: https://www.jamovi.org., accessed on December 12, 2025.
- Using Cliff’s Delta as a non-parametric effect size measure: An accessible web app and R tutorial. Pract Assess Res Eval.. 2024;29
- [Google Scholar]