Prospective cohort study, investigating the pre-post treatment effect of cosmetic injectable and surgical treatments on quality of life (primary outcome measure: FACE-Q Psychological, secondary outcome measure: FACE-Q Social), compared with a non-treated control group. Propensity score analysis is used to reduce confounding by indication.

Methods

Study design and setting

This is a prospective controlled nationwide multicenter cohort study with repeated measurements in adults receiving cosmetic treatment at a chain of cosmetic clinics in the Netherlands and untreated controls. The study is designed to evaluate changes in quality of life following cosmetic treatment over a follow-up period (botulinum toxin: 2 months; hyaluronic acid filler: 3 months; surgery: 1 year). Untreated controls are sisters of treated female participants and were recruited to provide a comparison group with partial genetic and socio-economic similarity. To reduce seasonal and broader temporal influences on quality of life, controls complete the baseline questionnaire within the same calendar start month and year as the corresponding treated participant.

The study includes a broad overall treated cohort and prespecified treatment strata. The primary comparison is treated participants versus untreated controls. Secondary comparisons are performed within treatment classes, and tertiary comparisons within individual treatment groups.

Participants

Eligible treated participants are adult clients who booked a cosmetic treatment appointment and are invited to participate before treatment. Eligible controls are untreated sisters of female treated participants. Participants are included if they complete both the baseline and the follow-up questionnaire. Treated participants are classified according to the treatment received during the observation window.

Treatment groups

Treatment exposure is classified using a prespecified dropdown list. These categories are grouped into clinically relevant strata for analysis.

The individual treatment options are:

botulinum toxin, glabella/frown; botulinum toxin, crow's feet; botulinum toxin, forehead; botulinum toxin, masseters; hyaluronic acid filler, lips; hyaluronic acid filler, zygoma; hyaluronic acid filler, jawline and/or chin; hyaluronic acid filler, marionet lines and/or nasolabial; surgery, upper blepharoplasty; surgery, labiaplasty; surgery, breast augmentation; and surgery, liposuction.

For hierarchical analyses, these are aggregated into the treatment classes botulinum toxin, hyaluronic acid filler, and surgery.

Procedures

Treated participants receive an invitation by their treating doctor to complete an online baseline questionnaire before treatment and an online follow-up questionnaire months later. Untreated controls completed the same questionnaires with follow-up questionnaires after 2, 3 and 12 months, without undergoing cosmetic treatment during the study period. Baseline data include demographic, socioeconomic, prior cosmetic treatment, psychological, and treatment-selection variables.

Age (continuous)

Sex at birth (male / female / other)

Highest completed educational level (elementary / high school / MBO / HBO / WO)

SES-WOA (PC4 postal code, CBS data)

Previous cosmetic injectables (no / yes, past 2 years / yes, over 2 years ago)

Previous cosmetic surgery

(no / yes, past 5 years / yes, over 5 years ago) Use of psychotropic medication (antidepressants; antipsychotics; sedatives/anxiolytics: yes / no)

Preoccupation with appearance (Dutch question: "Do you spend a lot of time thinking about an imperfection or shortcoming in your appearance?" (very much / quite a lot / not at all / a little)

Relationship status (yes / no)

At follow-up, treated participants also report which treatment they had undergone in the previous months.

Outcomes

The primary outcome measures are change in FACE-Q Psychological Wellbeing and the secondary outcome is FACE-Q Social Function from baseline to 2-month follow-up. Both questionnaires are administered in Dutch at baseline and follow-up.

FACE-Q Social Function consists of 8 items and FACE-Q Psychological Wellbeing of 10 items. Item responses are coded according to the Dutch response categories and summed or otherwise transformed according to the questionnaire scoring rules. For the main analyses, the baseline and follow-up scores of each FACE-Q scale are used.

Baseline covariates

Prespecified baseline covariates are selected to capture major determinants of treatment selection and potential confounding by indication. These are:

age, modeled continuously; sex at birth; relationship status; highest completed educational level; area-level socioeconomic status based on SES-WOA linked to four-digit postcode; history of prior cosmetic injectables; history of prior cosmetic surgery; psychopharmacological medication use, defined as use of medication for anxiety, depression, psychosis, or sleep problems; and appearance-related preoccupation.

In addition, baseline FACE-Q Psychological Wellbeing and baseline FACE-Q Social Function scores are included in the outcome models.

Statistical analysis

Baseline characteristics are summarized descriptively for treated participants and untreated controls.

To reduce confounding by indication, propensity score matching is used to estimate the average treatment effect on the treated. For each comparison, the propensity score is defined as the probability of undergoing the treatment of interest conditional on the prespecified baseline covariates. Propensity scores are estimated using logistic regression, with treatment status as the dependent variable and baseline covariates as independent variables.

Each treatment comparison are treated as a separate target trial emulation. Analyses are conducted hierarchically across three prespecified strata: any cosmetic treatment versus untreated controls; treatment class versus untreated controls, including surgery, botulinum toxin, and hyaluronic acid fillers; and individual treatment groups versus untreated controls.

Propensity score matching is performed separately for each comparison using nearest-neighbour matching without replacement. Both 1:1 and 1:2 matching are considered. A caliper width of less than 0.2 standard deviations of the logit of the propensity score is applied. A maximum of 5% unmatched treated participants is allowed. The final matching specification is selected based on post-matching balance.

Matching is considered successful if all absolute standardized mean differences were less than 0.20 and variance ratios were between 0.90 and 1.10. Among successful specifications, the configuration with the best overall covariate balance will be selected. For 1:2 matching, matching weights generated by the MatchIt package are used where applicable when not all treated participants received two matched controls.

After matching, treatment effects are estimated using weighted linear regression models with robust standard errors. For each FACE-Q outcome, the follow-up score is modeled as the dependent variable, with treatment group as the main independent variable and the corresponding baseline FACE-Q score included as a covariate. This analysis of covariance approach is chosen to improve precision and account for residual baseline differences after matching. Effect estimates is reported as adjusted mean differences with 95% confidence intervals.

Formal multiplicity correction will not be applied across the separate, non-nested target trial emulations, because each addressed a distinct causal question. To aid interpretation, a hierarchical Benjamini-Hochberg procedure across the three prespecified strata will be presented descriptively only. Confidence intervals and inference thresholds were not adjusted. Statistical significance is defined as a two-sided p value of 0.05 or lower.

Sensitivity analyses are performed to assess robustness. First, results are compared across the 1:1 and 1:2 matching strategies. Second, post-matching balance diagnostics will be evaluated for each analysis. Third, E-values were calculated for the estimated treatment effects as an indication of sensitivity to unmeasured confounding.

All analyses will be performed in R using the MatchIt, mice, and survey packages.

Ethics

The study was reviewed by the relevant institutional review board and was judged exempt from the Medical Research Involving Human Subjects Act (niet-WMO-plichtig). All participants provide informed consent before participation.

Reporting

The study is reported in accordance with the STROBE statement and the RECORD guidelines.

Inclusion Criteria:

• Clients who have booked a cosmetic treatment (injectables or surgery) in one of the contributing clinics in the Netherlands

Exclusion Criteria:

• Regular contra-indications as per clinic protocol / physician judgment

Clients seeking cosmetic treatments, who have already booked an appointment for consultation and/or treatment at a Dutch clinic.