Clinical Context

Wrinkles (also known as rhytids) and creases may appear in the face throughout the normal aging process because of a combination of genetic and environmental factors. These can be treated through different non-surgical options, including dermal fillers. This treatment option is typically an outpatient procedure with local anesthesia that can restore facial volume, diminish the appearance of facial wrinkles and lines, or soften creases.

Device Description

Dermal fillers, also known as injectable implants, soft tissue fillers, or wrinkle fillers are medical device implants approved by the FDA for use in helping to create a smoother and/or fuller appearance in the face, including nasolabial folds (wrinkles on the sides of the mouth that extend towards the nose often referred to as "smile lines"), cheeks, chin, lips, as well as for increasing the volume of the dorsum or back of the hand. Dermal fillers are regulated as Class III devices which are approved through the Premarket Approval process.

Restylane Kysse (Premarket Approval P140029/S021) is a hyaluronic acid-based dermal filler that can be injected into the lips to add fullness. It can also be injected into the skin above the lips to help smooth the wrinkles around your upper lip (perioral lines). The Premarket Approval submission was approved in March 2020.

Indications for Use

Restylane Kysse is indicated for injection into the lips for lip augmentation and the correction of upper perioral rhytids in patients over the age of 21; see Summary of Safety and Effectiveness Data (PDF).

Context of Clinical Outcome Assessment (COA) Use

The safety and effectiveness of dermal fillers are evaluated through clinical investigations. Inclusion criteria for the investigations include a validated scale that assesses wrinkle severity from a clinician’s perspective and/or a blinded live evaluator, who is also a clinician, for the proposed indication for use (clinician-reported outcomes, or ClinROs). COAs are also used as both safety and effectiveness endpoints. Often, safety endpoints are evaluated with patient-reported outcomes (PROs). The effectiveness assessment may be conducted using photographs evaluated after the study by a panel of blinded clinician evaluators (ClinRO).

Safety and effectiveness of Restylane Kysse was evaluated through a clinical investigation. Inclusion criteria for the investigation included the Medicis Lip Fullness Scale (MLFS) for assessment of the lips and the Wrinkle Assessment Scale (WAS) for assessment of the perioral lines by a blinded live evaluator (both ClinRO). The MLFS and WAS are validated scales used to assess the fullness of the lips and wrinkle severity from different perspectives.

COAs were also used in all predetermined safety and effectiveness endpoints. One PRO and two ClinROs were used to define safety endpoints. An Injection Site Reaction diary was used for patients to record the presence and level of intensity of pre-defined injection site adverse reactions (PRO). Treatment-emergent adverse events were also assessed and recorded by the clinician (ClinRO). A specifically trained study staff member performed Lip Safety Assessments, including evaluation of lip movement, function, and sensation (ClinRO). The change from baseline MLFS was used in the primary effectiveness endpoint by a blinded live evaluator (ClinRO) to assess non-inferiority of Restylane Kysse against a control in lip fullness augmentation eight weeks after last injection.

Secondary effectiveness endpoints aimed to assess:

• The appearance of perioral lines from the blinded live evaluator’s perspective (WAS; ClinRO),
• Lip improvement from the clinician’s perspective (Global Aesthetic Improvement Score (GAIS); ClinRO),
• Lip improvement from the patient’s perspective (GAIS and FACE-Q, both PROs).

Lessons Learned

Structured reports of adverse events from patients can serve as key endpoints evaluating safety, as demonstrated in the approval process of dermal fillers like Restylane Kysse. The effectiveness of treatment with an aesthetic device, like dermal fillers, has traditionally been assessed by clinicians and “blinded” live evaluators. More recent studies have included the patient’s assessment of treatment effectiveness.

Scientific assessments from multiple perspectives are particularly beneficial for aesthetic device evaluations. The inclusion of safety and effectiveness assessments from the patient perspective provides valuable information to the patient labeling for aesthetic devices, allowing future patients to make informed decisions regarding treatment options. For information on the specific studies for each approved dermal filler, see the FDA-Approved Dermal Fillers page.