Simulated Consumer Use of a Battery-Powered, Hand-Held, Portable Diode Laser (810 nm) for Hair Removal: A Safety, Efficacy and Ease-of-Use Study

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1 Lasers in Surgery and Medicine 39: (2007) Simulated Consumer Use of a Battery-Powered, Hand-Held, Portable Diode Laser (810 nm) for Hair Removal: A Safety, Efficacy and Ease-of-Use Study Ronald G. Wheeland, MD, FACP* Department of Dermatology, University of Missouri-Columbia, Columbia, Missouri Background and Objectives: Safety, efficacy and easeof-use of a hair removal diode laser for consumer use were evaluated. Study Design/Materials and Methods: The treatment group consisting of 77 appropriate users measured safety and efficacy from three self-administered treatments. The non-treatment group consisting of 44 inappropriate users measured safety from delivery of a single laser pulse. Results: The mean hair reduction was 61% 3 weeks after the first treatment, 70% 3 weeks after the second treatment, 60% 1 month after the third treatment, 24% 2 months after the third treatment, 6% 3 months after the third treatment, 41% 6 months after the third treatment, 31% 9 months after the third treatment, and 33% 12 months after the third treatment. The only observed side effect for appropriate users was transient erythema. Conclusions: In simulated consumer use, the laser was highly effective at removing hair with minimal side effects for appropriate users. Lasers Surg. Med. 39: , ß 2007 Wiley-Liss, Inc. Key words: diode laser; laser hair removal; self-treatment INTRODUCTION Many different techniques have been used for removing unwanted or excess hair. Temporary, but complete, hair removal can be accomplished easily by shaving, waxing, plucking, or application of chemical depilatories [1]. However, for years the only permanent method of hair removal had been electrolysis, which required insertion of a solid fine-gauge needle into each hair follicle and then passing low magnitude direct electrical current through soft tissue to destroy hair follicles [2]. Unfortunately, this technique was painful, tedious, expensive, and could also produce scarring and permanent hypopigmentation. As a result of these adverse effects and the continued desire for greater convenience, the search for an alternative form of treatment using lasers was begun more than a decade ago. A concept known as selective photothermolysis [3] was developed which predicted that it would be possible to selectively injure hair follicles by precisely delivering laser light of the proper wavelength, pulse duration, and pulse energy. Precise damage to hair follicles containing darkly colored hairs was possible by laser light being selectively absorbed by the melanin found within the hair shaft. The precision offered by the concept of selective photothermolysis results in minimal collateral damage to the surrounding tissues [4]. A number of different wavelengths of light have been used to provide the desired precision for laser hair removal [5] since the absorption spectrum for melanin is very broad. One of the first lasers designed for this purpose employed the normal mode ruby laser [4]. Red light from this laser was selectively absorbed by melanin found in the structural elements of the hair shaft as well as melanocytes that are interspersed between the matrix cells found in the bulb of the hair [6]. The major limiting factor was absorptive interference caused by melanin found within the epidermis that not only reduced the amount of light reaching the bulb of the hair follicle but also could injure the skin surface and result in permanent hypopigmentation in some cases. In addition, since multiple expert treatments were virtually always necessary due to variations in hair growth cycles [6,7], it was also a very expensive process. While modifications in the ruby laser technique for hair removal were attempted, including cooling the skin surface [8] prior to the laser impact and lengthening the pulse duration [9] to reduce pain and minimize epidermal injury, the ruby laser technique still did not provide the most ideal results. As a consequence, other wavelengths of laser and filtered flashlamp light have been investigated for hair removal. Over the past 10 years, the use of the pulsed diode lasers for hair removal has become one of the most successful aesthetic laser applications performed by dermatologists [10]. The physician-use Class IV lasers typically produce energy fluences (energy densities) ranging from 10 to 60 J/cm 2 and pulse durations from 5 to 100 milliseconds at a nominal wavelength of 800 nm. With extensive worldwide use by licensed medical practitioners, the safety and efficacy of these devices has been well established [11]. A new, pulsed diode laser intended for at-home consumer use for hair removal has recently been developed (SpectraGenics, Inc.; Pleasanton, CA). Utilizing new technology, this 810 nm wavelength, battery-powered, hand-held laser can produce energy fluences, and pulse durations Contract grant sponsor: SpectraGenics, Inc. *Correspondence to: Ronald G. Wheeland, MD, FACP, Professor and Chief of Dermatologic Surgery, Department of Dermatology, University of Missouri Columbia, One Hospital Drive, Columbia, Missouri ronwheeland@gmail.com Accepted 4 May 2007 Published online in Wiley InterScience ( DOI /lsm ß 2007 Wiley-Liss, Inc.

2 SIMULATED CONSUMER USE OF A PORTABLE DIODE LASER 477 which are similar to the FDA-cleared physician-use devices, but at a much lower cost (Fig. 1). The device provides three energy fluence settings of high (22.0 J/cm 2 ), medium (17.5 J/cm 2 ), and low (13.0 J/cm 2 ) with nominal pulse widths of 600, 450, and 300 milliseconds, respectively. The spot size is 1.0 cm in diameter. In addition, this device employs eye-safety technology that eliminates retinal eye hazards, making it a Class I laser that does not require protective eyewear during treatment. The typical time to treat an area will vary depending upon the size of the body location being treated. Typical treatment time for an average axilla is about minutes. It is anticipated that this low-cost, eye-safe, portable device could make laser hair removal much more widely available and appropriate for over-the-counter consumer use. MATERIALS AND METHODS Objective This clinical study was designed to demonstrate the safety, short and long-term efficacy and usability of a portable, hand-held diode laser. This study was also designed to show that consumers are able to effectively use the package labeling to determine whether they are suitable candidates to use the device and achieve satisfactory results in a simulated home-use environment. Study Design The study was designed as a single-site, two-armed study with the Treatment Group (TG) intended to measure safety and efficacy for the intended or appropriate users of the device, and the Non-Treatment Group (NTG) designed to Fig. 1. The battery-powered hand-held portable diode laser used in this study; (SpectraGenics, Inc., Pleasanton, CA). measure safety for unintended or inappropriate users of the device. Appropriate users are defined as individuals with naturally light brown to black hair in the treatment area and Fitzpatrick Skin Types I IV. Inappropriate (contraindicated) users are individuals who do not meet one or both of these criteria; that is, those individuals with naturally white, gray, red, or blond hair, for whom the device would be ineffective, or those with Fitzpatrick Skin Types V and VI, for whom the device might cause inadvertent injury to the skin. Study subjects were screened and enrolled into a sample pool designed to match United States national demographics for race/ethnicity, age and education to be most representative of the expected domestic consumer market for the device. Emphasis was placed on obtaining a wide variety of skin type and hair color combinations since these characteristics are the primary factors that affect safety and efficacy. Exclusion criteria included any prior permanent hair removal treatment or the use of plucking, tweezing, waxing, or chemical depilatories in the anticipated treatment area for 12 weeks prior to initiation of this study. The study was performed at a single site (Section of Dermatology, University of Arizona Health Sciences, Tucson, AZ) and all study subjects were recruited from the immediate surrounding area. All treatments and observations were performed at the dermatology clinic in a dedicated room equipped with the test device and all supplies typical of the home environment. Enrolled subjects were provided representative retail labeling consisting of a printed user manual, printed quick reference card and an 8-minute instructional video. After having an opportunity to review these materials, the subjects were asked to determine whether they were appropriate or inappropriate candidates to use this device. The accuracy of the self-selection process was quantified as a measure of the effectiveness of the package labeling. Appropriate users were assigned to the TG and performed three self-administered treatments at 3-week intervals with no instruction other than the package labeling. Each TG subject treated two self-chosen body sites from the following list: axilla, leg, arm, abdomen, chest, upper lip, bikini, or nape of the neck (men only). Subjects were allowed to treat symmetric sites, for example, both axillae, if desired. The treatments were performed ona3cm 3 cm area at each body site. For consistency purposes, each treatment area was identified from visit to visit by the clinical staff. Treatment templates with physical landmarks and digital photographs from the initial visit were used by the clinical staff to re-identify and mark the treatment area at each visit with red ink for easy identification by study subjects. Other than identifying the treatment region, all study subjects performed each treatment entirely themselves, including choosing the energy fluence from the available high (22.0 J/cm 2 ), medium (17.5 J/cm 2 ) and low (13.0 J/cm 2 ) settings. Device labeling instructed subjects that higher settings were likely to achieve better results, and to choose the highest setting possible without excessive discomfort.

3 478 WHEELAND Data, including physical hair counts, side effects and ease of use, were collected at every treatment visit and also at the 1-, 2-, 3-, 6-, 9-, and 12-month follow-up visits after completing the third treatment. Manual hair counts using a magnifying glass were only made on the central 2 cm 2 cm region of each 3 cm3 cm treatment site. To facilitate counting, subjects were required not to shave the treatment area for 1 week prior to the visit and the hair was clipped to a length of 1 3 mm just prior to the count. Subjects were allowed to shave between visits, but not to perform any plucking, chemical epilation or other types of hair removal. Clinical staff closely observed each subject for any possible side effects immediately after each treatment. Photographs were also taken before and after each treatment. In order to obtain usability data, the clinical staff also observed the first treatment. Subjects answered usability, treatment and satisfaction questionnaires at selected visits. Inappropriate users were assigned to the NTG and were given a single, staff-administered laser pulse at the maximum energy fluence of the device on a non-cosmetic, hairbearing site mutually chosen by the subject and the clinical staff. Side effect observations were made immediately and 1 day after delivery of the single test pulse. The Principal Investigator scheduled additional follow-up visits as needed. The NTG study arm was designed to determine the worst-case incidence of undesired side effects should inappropriate individuals, particularly contraindicated users with Fitzpatrick Skin Types V or VI, use the device at the maximum fluence. RESULTS Sample Characteristics A total of 132 subjects were enrolled in the study with 88 enrolled in the TG and 44 enrolled in the NTG. A total of 77 (87.5%) of the TG subjects completed the protocol through the 3-month post-treatment follow up visit and were deemed to have completed the study per the protocol definition. A total of 70 (79.5%) of the TG subjects had additional follow up visits at 6, 9, and 12 months after the third treatment. All 44 (100%) of the NTG subjects completed the protocol. The reasons given for the subjects TABLE 1. Demographics of the Study Subjects (Subjects Completing thru the 3-Month Follow-Up Visit) Treatment group (TG) Non-treatment group (NTG) Combined total US population a # % # % # % % Gender Male Female Total Age þ Total Race/Ethnicity White/Caucasian Hispanic/Latino Black/African-American American Indian/Alaskan Native Asian American Hawaiian/Pacific Islander Other Reporting 2 or more Total Education Grammar or junior high school High school or GED Some college Bachelor s degree Master s degree or higher Total a Estimated from 2000 US Census data.

4 SIMULATED CONSUMER USE OF A PORTABLE DIODE LASER 479 discontinuing the study included: withdrawal of consent (5), lost to follow-up (3), investigator or sponsor request to withdraw subject (1), subject discomfort or pain (1), and subject felt device was too awkward to use (1). Five of the seven subjects who did not complete the additional 6-, 9-, and 12-month follow-up visits were lost to follow up and two subjects performed another type of hair removal procedure on the treatment area. The demographic characteristics of the subjects completing the study (Table 1) show that the study group was predominately female (84%) with a distribution of age, race, ethnicity, and education similar to demographics from the 2000 United States national census. Due to difficulty in recruiting Asian-Americans at the study location, this racial or ethnic group is under-represented. However, skin type and hair color combinations reflective of Asian- Americans are represented. The skin type and hair color distribution of our TG (Table 2) consisted of 15 individuals with black hair color, 49 with dark brown hair color and 13 with light brown hair color. The TG group consisted of 8 individuals with Fitzpatrick Skin Type I, 19 with Fitzpatrick Skin Type II, 34 with Fitzpatrick Skin Type III and 16 with Fitzpatrick Skin Type IV. The NTG (contraindicated users) consisted of 2 subjects with hair color that was too light to be effectively treated, 12 subjects with Fitzpatrick Skin Type V and 30 subjects with Fitzpatrick Skin Type VI skin types too dark to allow safe treatment without possible risks of blister formation or hypopigmentation. Each TG subject treated two body sites of their choosing. The treated body sites (Table 3) included: the axilla (64%), leg (25%), arm (4%), abdomen (3%), chest (1%), upper lip (1%), and bikini area (1%). It is believed that the bikini area and upper lip were under-represented compared to market representation due to privacy concerns with the required photography and physical hair counts. The NTG received a single test pulse at a non-cosmetic, hair-bearing location chosen by mutual agreement between the subject and clinical staff. The test site included the axilla (5%), leg (41%), arm (50%), and nape of the neck (5%). Efficacy As described in the Methods section, the primary measure of the effectiveness of the hair removal self-treatments was the quantitative hair count performed at each visit. The hair count reduction is defined as the percentage reduction from the baseline count taken at the first visit. Secondary measures of efficacy were made by questionnaires in which the subjects were asked for their selfassessment of hair count reduction, hair regrowth characteristics, post-treatment skin texture and overall level of satisfaction. Quantitative hair counts. The mean hair count reduction for all self-administered treatments in the TG study was 60.6% 3 weeks after the first treatment, 69.8% 3 weeks after the second treatment, 59.5% 1 month after the third treatment, 23.7% 2 months after the third treatment, 6.2% 3 months after the third treatment, 40.6% 6 months after the third treatment, 30.5% 9 months after the third treatment, and 32.7% 12 months after the third treatment (Fig. 2 and Table 4). The width of the 95% confidence intervals are 4.2%, 4.3%, 4.7%, 7.1%, 7.5%, 5.9%, 6.2%, and 5.2%, respectively. The reduction in hair counts from baseline was statistically significant (P<0.01) at all visits, except at visit 6. The reduction in hair counts by hair color showed no clear trend in efficacy from light brown to dark brown to black hair (Fig. 3 and Table 5). For example, the mean hair count reduction at visit 3 is % for light brown hair, % for dark brown hair, and % for black hair. At the 2-month follow-up visit, the hair reduction is marginally statistically better for light brown hair % than dark brown hair % and black hair %, and remains marginally better at subsequent visits. For all hair colors, the hair count reduction was statistically significant (P<0.01) at all visits, except at visit 6 and for black hair at visit 8. The hair count reduction as a function of Fitzpatrick Skin Type also showed no clear trend in efficacy (Fig. 4 and Table 6). The mean hair count reduction at visit 3 was TABLE 2. Skin Type and Hair Color of the Study Subjects Fitzpatrick skin type Treatment group (TG) Hair color I II III IV V VI Total Black Dark brown Light brown Total Non-treatment group (NTG) Hair color I II III IV V VI Total Black Dark brown Light brown White, gray, blond, red Total

5 480 WHEELAND TABLE 3. Body Site Distribution Body site Treatment group (TG) Non-treatment group (NTG) # % # % Axilla Leg Arm Abdomen Chest Upper lip Bikini Neck Total % 10.9% for Skin Type I, % for Skin Type II, % for Skin Type III and % for Skin Type IV. The hair count reduction was statistically significant (P<0.01) for more than 2 months after the third treatment for all skin types except Skin Type II. At the 3-month followup visit, the reduction from baseline was statistically significant only for Skin Type I. At the 6-, 9-, and 12-month follow-up visits, the reduction from baseline was statistically significant for all skin types except Skin Type II at visit 8. Hair reduction by body site (Fig. 5 and Table 7) shows moderate, but significant, differences in efficacy between the axilla, leg, and arm. The greatest reduction in hair counts occurred on the legs, followed by the arms and then the axillae. The hair reduction was statistically significant (P<0.01) at all visits, except for the axilla at the 2-month follow-up visit, the axilla and arm at the 3-month follow-up visit, and the arm at the 6-, 9-, and 12-month follow-up visits. There were insufficient samples of the arm body site at the 6-, 9-, and 12-month follow-up visits to reach statistical significance. Only data for the axillae, legs, and arms are given since the other sites had insufficient sample sizes to be statistically significant. Subjective assessments Hair count reduction. The subjects assessed the reduction in hair counts themselves at selected visits following the first treatment using a six-category scale. The predominant responses were 75 99% reduction 3 weeks following the first treatment, 75 99% reduction 3 weeks following the second treatment, 75 99% reduction 1 month after the third treatment, 75 99% reduction 2 months after the third treatment, no reduction 3 months following the third treatment, and 50 74% reduction at 12 months after the third treatment (Table 8). The mean self-assessed percent reduction inferred from these categories were 57%, 65%, 60%, 37%, 28%, and 31% for the same visits. These numbers correlate well with the quantitative measurements of 61%, 70%, 60%, 24%, 6%, and 33% reduction for the same visits (Table 4 and Fig. 2). Hair regrowth characteristics. At selected follow-up visits, the subjects were asked to assess the character of the hair that regrew after treatment. A total of 87% of subjects stated that the hair that grew back 1 month after the third treatment was finer, 70% felt is was lighter and 85% stated the hair was less noticeable than the pre-treated hair (Table 9). At this same visit, 9% of subjects felt the regrown hair had about the same degree of coarseness, 25% felt the regrowing hair had about the same color, and 10% felt the regrowing hair had about the same visibility as the pre-treatment hair (Table 9). By the 3-month follow-up visit, the percentage of subjects who felt the regrowing hair was lighter and less noticeable was roughly the same as those who felt it was unchanged. However, 68% of subjects Fig. 2. Percent hair reduction for all sites.

6 TABLE 4. Percentage Hair Reduction for all Sites All sites Visit 2 (3 weeks after 1st tx) SIMULATED CONSUMER USE OF A PORTABLE DIODE LASER 481 Visit 3 (3 weeks after 2nd tx) Visit 4 (1 month after 3rd tx) Visit 5 (2 months after 3rd tx) Visit 6 (3 months after 3rd tx) Visit 7 (6 months after 3rd tx) Visit 8 (9 months after 3rd tx) Visit 9 (12 months after 3rd tx) Number of sites Mean 95% confidence interval (%) Std error (%) Median (%) t-test P-value <0.01 <0.01 <0.01 < <0.01 <0.01 <0.01 still felt the hair was finer in caliber than prior to treatment. At the 12-month follow-up visit, 64% of the subjects felt that the regrowing hair was less noticeable than prior to treatment, 71% of subjects felt that the hair was finer than prior to treatment, and 44% of subjects felt that the hair that regrew was lighter than prior to treatment. Very few subjects felt that the regrowing hair was thicker, darker, or more noticeable at any of the follow-up visits. Skin characteristics. Compared to the subjects traditional hair removal method, 38% of subjects assessed their skin (Table 10) after the third laser treatment as less irritated and having fewer bumps. About 20% felt it produced fewer nicks, cuts, or abrasions, 43% felt it produced smoother skin and 20% felt the laser treatments produced softer skin. About 37% of respondents were either not sure, or felt it made no difference in their skin texture. The skin textural benefits of the test device were perceived as greatest when the hair reduction was greatest and diminished as the hair reduction diminished. Subject satisfaction. The TG subjects overall satisfaction also varied as a function of the study visit (Table 11 and Fig. 6). This went from a predominant opinion of being satisfied after the first treatment, to being very satisfied 3 weeks after first treatment, to extremely satisfied 3 weeks after the second treatment, to very satisfied 1 month after the third treatment, to satisfied at 2, 3, and 12 months following the third treatment. This satisfaction score correlates strongly with the quantitative reduction in hair counts as well as the subjective assessments of the hair count reduction. The maximum efficacy occurred at the third visit when 42% of subjects reported being extremely satisfied and 32% of subjects reported being very satisfied with the results of treatment. Safety The clinical staff carefully evaluated every subject at each study visit for both the TG and the NTG for possible side effects or adverse events. The incidence of each side Fig. 3. Percent hair reduction by hair color.

7 482 WHEELAND TABLE 5. Percentage Hair Reduction by Hair Color Hair Color Black Dk Brown Lt Brown All Visit 2 (3 weeks after 1st tx) Number of sites Mean 95% confidence interval (%) Standard error (%) Median (%) t-test P-value <0.01 <0.01 <0.01 <0.01 Visit 3 (3 weeks after 2nd tx) Number of sites Mean 95% confidence interval (%) Standard error (%) Median (%) t-test P-value <0.01 <0.01 <0.01 <0.01 Visit 4 (1 month Number of sites Mean 95% confidence interval (%) Standard error (%) Median (%) t-test P-value <0.01 <0.01 <0.01 <0.01 Visit 5 (2 months Number of sites Mean 95% confidence interval (%) Standard error (%) Median (%) t-test P-value <0.01 <0.01 <0.01 <0.01 Visit 6 (3 months Number of sites Mean 95% confidence interval (%) Standard error (%) Median (%) t-test P-value Visit 7 (6 months Number of sites Mean 95% confidence interval (%) Standard error (%) Median (%) t-test P-value <0.01 <0.01 <0.01 <0.01 Visit 8 (9 months Number of sites Mean 95% confidence interval (%) Standard error (%) Median (%) t-test P-value 0.01 <0.01 <0.01 <0.01 Visit 9 (12 months Number of sites Mean 95% confidence interval (%) Standard error (%) Median (%) t-test P-value <0.01 <0.01 <0.01 <0.01

8 SIMULATED CONSUMER USE OF A PORTABLE DIODE LASER 483 Fig. 4. Percent hair reduction by skin type. effect (Table 12) was calculated as the percentage of subjects exhibiting that side effect at any visit. On the posttreatment questionnaire TG subjects were also asked whether they experienced any side effects and, if so, to describe them (Table 12, other, self-reported ). For the intended users of this device, TG subjects, the only observed immediate post-treatment side effect was erythema (transient redness), which occurred in 33% of the subjects (29 of 88). On a scale of 0 (none) to 4 (severe), all cases of erythema were rated as 1 (minimal) or 2 (moderate), in 25 and 4 subjects, respectively. All erythema resolved spontaneously, often in less than 30 minutes while the subject was still at the treatment facility. The clinical staff noted no edema, epidermal erosion, crusting, blistering, hypopigmentation, hyperpigmentation, or other side effects. In addition, no side effect persisted to the next study visit. The following nine types of side effects were selfreported on the questionnaire by subjects: skin abrasion (1), tenderness in the treatment area (1), burning sensation in the treatment area (1), folliculitis (1), skin irritation (2), pain (4), stinging (2), tingling (1), and skin dryness (1). Three subjects reported more than one of these side effects. For the contraindicated users of this device, NTG subjects, side effects were evaluated immediately postpulse and 24-hours later. Immediately post-pulse, there was no erythema observed in these darker skin types. Immediately post-pulse, there were two instances (5%) of a mild blister. At the 24-hour follow-up visit, a blister was observed in 8% (1/12) of Fitzpatrick Skin Types V and in 33% (10/30) of Fitzpatrick Skin Types VI, demonstrating that risk of injury increases for contraindicated users with the darkest skin types. No other side effects were observed at the 24-hour follow-up visit. On a scale of 1 (none) to 4 (severe), eight blisters were rated as 2 (minimal) and three were rated as 3 (moderate). Additional follow-up was obtained for the three subjects exhibiting a moderate blister. In all of these subjects, the blister was observed to have resolved with slight hypopigmentation, hyperpigmentation, and/or slight induration at the test site. No medical intervention, such as the application of topical antibiotics or other therapy, was provided or needed by any of the NTG subjects, including those with blisters. No side effects were reported or observed in the two light skinned (Fitzpatrick Skin Types I II) with red, gray, white, or blond hair that were enrolled in the NTG. Pain Levels All subjects were asked to assess the pain level after each treatment. For the TG, the predominant description of the pain level was slight in 36% of subjects at the first treatment, 41% at the second treatment and 42% at the third treatment (Table 13). Only one subject in 88 (1%) felt the pain level was severe enough to request being dropped from the study. This was predictable given the fact that this subject had black hair, Fitzpatrick Skin Type IV and selected the nape of the neck, where the hair density was very high, for treatment. The overall pain level for the TG decreased over the course of the three treatments, with the mean pain level decreasing from 2.0 to 1.5 on a scale of 0 4. This is likely a function of fewer hairs remaining at the treatment site during the course of the study, resulting in less pain. For the NTG, who received one test pulse at maximum energy fluence, the two subjects who had light hair color and light skin (Fitzpatrick Skin Type I II) reported having no pain. For the darker skin types (Fitzpatrick Skin Types

9 484 WHEELAND TABLE 6. Percentage Hair Reduction by Skin Type Fitzpatrick skin type I II III IV All Visit 2 (3 weeks after 1st tx) Number of sites Mean 95% confidence interval (%) Standard error (%) Median (%) t-test P-value <0.01 <0.01 <0.01 <0.01 <0.01 Visit 3 (3 weeks after 2nd tx) Number of sites Mean 95% confidence interval (%) Standard error (%) Median (%) t-test P-value <0.01 <0.01 <0.01 <0.01 <0.01 Visit 4 (1 month Number of sites Mean 95% confidence interval (%) Standard error (%) Median (%) t-test P-value <0.01 <0.01 <0.01 <0.01 <0.01 Visit 5 (2 months Number of sites Mean 95% confidence interval (%) Standard error (%) Median (%) t-test P-value < <0.01 <0.01 <0.01 Visit 6 (3 months Number of sites Mean 95% confidence interval (%) Standard error (%) Median (%) t-test P-value < Visit 7 (6 months Number of sites Mean 95% confidence interval (%) Standard error (%) Median (%) t-test P-value <0.01 <0.01 <0.01 <0.01 <0.01 Visit 8 (9 months Number of sites Mean 95% confidence interval (%) Standard error (%) Median (%) t-test P-value < <0.01 <0.01 <0.01 Visit 9 (12 months Number of sites Mean 95% confidence interval (%) Standard error (%) Median (%) t-test P-value <0.01 <0.01 <0.01 <0.01 <0.01

10 SIMULATED CONSUMER USE OF A PORTABLE DIODE LASER 485 Fig. 5. Percent hair reduction by body site. V and VI), 26% described the pain as slight, 31% as some pain, 26% as moderate, and 17% as severe pain. As expected, the mean pain level for the NTG was greater than for the TG on the first visit (2.3 on a scale of 0 4, which compares with 2.0 from the mean of the TG). Usability of the Device and its Labeling The effectiveness of product labeling and ease-of-use were both measured in several ways. The most obvious measure of usability was whether or not the device was used safely and whether it achieved good results in actual use. Those findings have been described above in the efficacy and safety sections. Based on the data that TG users achieved a high percentage of hair removal with minimal or no side effects it can be concluded that the product labeling was effective at the basic usability level for the intended users. The product labeling gave the TG users sufficient information so that they were able to turn the device on, select the appropriate energy fluence, trigger a pulse, apply the light to the skin, overlap the treatment pulses, and perform the other actions necessary for safe and effective treatment. Detailed usability information was obtained by the recorded observations (Table 14) made by the clinical staff during each subject s first treatment. As shown, 99% of subjects did shave prior to use (as recommended in the labeling), 77% adjusted fluence settings (which indicates an understanding of that control), no subjects performed any unsafe actions and 99% of subjects were judged to have understood how to properly operate the device by the end of the first treatment. This study also suggests (Table 14) that the device had an appropriate range of energy fluences, adequate energy fluence controls and understandable energy fluence labeling. About 31% of subjects used the high setting exclusively, 24% used the low exclusively and 39% used a combination of different energy fluence settings. Since only 2 subjects (2%) discontinued the study due to discomfort, the range of energy fluences provided by the device allowed nearly everyone in the TG to select an appropriate energy fluence for treatment that was low enough to be tolerated and yet high enough to be efficacious. The product labeling recommended overlapping treatment pulses by 50% and using 50 pulses in a treatment region of one square inch. It was observed that 80% of subjects applied 49 or greater pulses, 17% applied pulses, 1% applied pulses, and 2% applied 11 or fewer pulses (Table 14). Thus, subjects appear to have generally understood the labeling recommendation and need to overlap the pulses to obtain the best results. Another important labeling assessment was to measure the accuracy by which subjects determined if they were appropriate users based upon the labeling for using this device. Of the subjects deemed appropriate users by the clinical staff, 100% (88 of 88) properly selected themselves as appropriate users. Of the subjects who were deemed inappropriate users by the clinical staff, 82% properly selected themselves as inappropriate users. Only eight inappropriate subjects (18%) incorrectly deemed themselves as appropriate candidates for treatment. The labeling usability was also assessed by a questionnaire that asked questions about device usage and side effects (Table 15). As shown, the subject responses were 89 99% correct regarding device usage questions. The high degree of accuracy on these questions is consistent with the efficacy results and the staff observations described above. Side effects were classified in the labeling as either normal

11 486 WHEELAND TABLE 7. Percentage Hair Reduction by Body Site Body site Axilla Leg Arm All Visit 2 (3 weeks after 1st tx) Number of sites Mean 95% confidence interval (%) Standard error (%) Median (%) t-test P-value <0.01 <0.01 <0.01 <0.01 Visit 3 (3 weeks after 2nd tx) Number of sites Mean 95% confidence interval (%) Standard error (%) Median (%) t-test P-value <0.01 <0.01 <0.01 <0.01 Visit 4 (1 month Number of sites Mean 95% confidence interval (%) Standard error (%) Median (%) t-test P-value <0.01 <0.01 <0.01 <0.01 Visit 5 (2 months Number of sites Mean 95% confidence interval (%) Standard error (%) Median (%) t-test P-value 0.07 <0.01 <0.01 <0.01 Visit 6 (3 months Number of sites Mean 95% confidence interval (%) Standard error (%) Median (%) t-test P-value 0.30 < Visit 7 (6 months Number of sites Mean 95% confidence interval (%) Standard error (%) Median (%) t-test P-value <0.01 < <0.01 Visit 8 (9 months Number of sites Mean 95% confidence interval (%) Standard error (%) Median (%) t-test P-value <0.01 < <0.01 Visit 9 (12 months Number of sites Mean 95% confidence interval (%) Standard error (%) Median (%) t-test P-value <0.01 < <0.01

12 SIMULATED CONSUMER USE OF A PORTABLE DIODE LASER 487 TABLE 8. Self-Assessed Percentage Reduction in Hair Visit 2 (3 weeks after 1st tx) Visit 3 (3 weeks after 2nd tx) Visit 4 (1 month Visit 5 (2 months Visit 6 (3 months Visit 9 (12 months Reduction # % # % # % # % # % # % Total Mean (0 5 scale) Mean (0 100% scale) 57% 65% 60% 37% 28% 31% and expected (mild pain during treatment, mild temporary redness immediately after treatment, or mild transient swelling immediately after treatment) or unexpected and deserving of medical advice (blistering, pigmentary changes, or skin infection). About 84% of subjects correctly answered that mild pain during treatment was normal, 80% that mild transient redness was normal, and 67% that mild swelling was normal. Those that incorrectly answered these questions (16 33%) would tend to seek medical attention when it was not warranted, which is a conservative response. For the unusual and more serious side effects, 91% correctly answered that blistering was not normal, 81% correctly answered that pigmentary changes were atypical and 95% correctly answered that skin infection was unanticipated. Those that incorrectly answered these questions (5 19%) would be expected to not follow the medical advice recommended in the labeling, which is not a conservative outcome. DISCUSSION To summarize, the study showed in simulated consumer use: * Excellent short-term single-treatment hair removal. The device substantially reduced the number of hairs after one treatment. The mean percentage hair count reduction from all sites was 61% at 3 weeks after the first treatment. A full 84% of treatment sites had cosmetically meaningful hair removal (defined as more TABLE 9. Self-Assessed Characterization of Regrown Hair Visit 4 (1 month Visit 5 (2 months Visit 6 (3 months Visit 9 (12 months Hair regrowth: # % # % # % # % Coarseness Finer Thicker About the same No answer given Total Color Lighter Darker About the same No answer given Total Obviousness Less noticeable More noticeable About the same No answer given Total

13 488 WHEELAND TABLE 10. Self-Assessed Skin Texture Changes Visit 2 (3 weeks after 1st tx) Visit 3 (3 weeks after 2nd tx) Visit 4 (1 month Visit 5 (2 months Visit 6 (3 months Visit 9 (12 months Skin texture change # % # % # % # % # % # % Less skin irritation and bumps Fewer nicks, cuts, or abrasions Smoother skin Softer skin No difference Not sure Number of subjects at this visit Note: Subjects were allowed to check as many answers to this question as were applicable. TABLE 11. Overall Satisfaction Visit 1 (1st tx) Visit 2 (3 weeks after 1st tx) Visit 3 (3 weeks after 2nd tx) Visit 4 (1 month Visit 5 (2 months Visit 6 (3 months Visit 9 (12 months Satisfaction # % # % # % # % # % # % # % (0) Not satisfied (1) Slightly satisfied (2) Satisfied (3) Very satisfied (4) Extremely satisfied Total Mean

14 SIMULATED CONSUMER USE OF A PORTABLE DIODE LASER 489 Fig. 6. Overall (TG) subject satisfaction. than 30% hair reduction) after the first treatment. This is especially impressive considering that this was the first use of the device by the subjects and that subjects learned how to use the device solely from the device s proposed instructions for use. * Excellent sustained hair removal with periodic treatments. The hair reduction was consistent after repeat treatments. The mean percentage hair count reduction from all sites was 61% at 3 weeks after the first treatment, 70% at 3 weeks after the second treatment, and 60% at 4 weeks after the third treatment. The subjects showed sustained hair removal (64% on average) while conducting the periodic treatments, as outlined in the device s proposed instructions for use. * Substantial long-term hair count reduction without continued, periodic treatments. Long-term hair reduction at 6, 9, and 12 months was substantial. The mean percentage hair count reduction from all sites was 41% at 6 months after the last treatment, 31% at 9 months after the last treatment, and 33% at 12 months after the last treatment. That is, the hair count was permanently reduced by 35% after just three self-treatments. * The hair that regrew was perceived to be finer and lighter by subjects. * The results varied slightly by user and body site with some of the variation due to biological differences such as hair color and some variation due to how well the subjects used the device. TABLE 12. Side Effects and Adverse Device Effects Treatment group (TG) Non-treatment group (NTG) Side effects/ade s Number Incidence (%) Number Incidence (%) Erythema Edema Erosions Crusting Burn/Blistering Hypopigmentation Hyperpigmentation Infection Scarring Other (self-reported) Sample size (# subjects) TABLE 13. Self-Assessed Pain Levels Treatment group (TG) Non-treatment group (NTG) Visit 1 (1st tx) Visit 2 (3 weeks after 1st tx) Visit 3 (3 weeks after 2nd tx) Light hair and skin types Dark hair and skin types Pain # % # % # % # % # % (0) None (1) Slight pain (2) Some pain (3) Moderate pain (4) Severe pain Total Mean

15 490 WHEELAND TABLE 14. Staff Observations During the First Treatment Yes No Did the user: # % # % Shave? Adjust power settings? Do anything unsafe? Understand how to properly operate device? Have anything unexpected happen? Have to stop early due to discomfort? Observed power settings High Medium 6 7 Low Combination of settings Observed number of pulses 49þ < * The hair removal success did not depend significantly on hair color or skin type for indicated users. * The only side effects for appropriate users were mild-tomoderate transient erythema and slight pain during treatment. * The proposed consumer product labeling was usable and effective. The study demonstrated that users were provided with sufficient information to achieve effective results and use the device safely. * The study showed, as expected, that the fluence and pulse durations used in this device are contraindicated only for Fitzpatrick Skin Types V and VI, and that a transient, self-resolving injury in the form of a skin blister may occur only if the device is used by contraindicated users. The absence of significant hair reduction at 3 months after the final treatment, followed by convincing hair reduction at 6, 9, and 12 months, results from the natural cycle of body hair in humans [12 14,19 23]. One plausible explanation of this effect is illustrated in Figure 7. Several assumptions are made in this explanation, based upon data found in the published scientific literature: (1) only anagen hairs are damaged by treatment with this diode laser, (2) hair follicles that are damaged are permanently disabled, and (3) the human hair growth cycle and time phasing affect the hair count [3,5,11 30]. As Figure 7 illustrates: (1) Just before treatment (baseline), each hair is either anagen or telogen. In the illustration of Figure 7, there TABLE 15. Labeling Usability Topic of multiple-choice question Responses (#) Correct (#) Correct (%) Device usage Power setting for best results Power setting for lowest pain LEDs indicating high power setting Pre-treatment shaving as recommended Angle of device on the skin Percentage overlap for best results Side effects Mild pain during treatment as anticipated Mild transient redness as anticipated Mild transient swelling as anticipated Blistering as unanticipated Pigment changes as unanticipated Skin infection as unanticipated

16 SIMULATED CONSUMER USE OF A PORTABLE DIODE LASER 491 Fig. 7. The effect of the hair growth cycle on hair counts. are six anagen hairs and six telogen hairs (a 50:50 ratio). The baseline anagen hair count is six in this example. Note that only anagen hairs were counted in this study, because the treatment site was shaved approximately 1-week prior to the baseline hair count. (2) In the short-term (1 month follow-up), the hairs generally remain in the same phase because the time interval in this particular clinical study is shorter than the natural hair growth cycle [22,23]. Thus, anagen hairs remain anagen and telogen hairs remain telogen. For the purposes of this illustration (Fig. 7), the laser is assumed 67% effective against anagen hairs and disables 4 of the 6 anagen hairs, and none of the 6 telogen hairs. The measured hair count would be 2 growing hairs compared to 6 at baseline, which is a short-term efficacy measurement of 67%. (3) In the mid-term (3-month follow-up), the hairs are generally of the opposite phase than during treatment because the time interval is about one hair growth cycle. Thus, most hairs that were anagen at baseline are now telogen, and vice versa. The anagen hair count of Figure 7 now shows 6 anagen hairs (these were telogen at baseline) versus 6 baseline hairs. Accordingly, there is a misleading mid-term efficacy of 0%, a figure that simply reflects the change in phase rather than the true effectiveness of the treatment. (4) In the long-term (6-month or longer follow-up), the hairs have lost the specific phase relationship with each other because each hair has a different phase

17 492 WHEELAND duration and the hairs are randomly distributed within each phase. Thus, a hair that was anagen (or telogen) in the treatment period is now equally likely to be either anagen or telogen, unlike the case at the 3-month follow-up. The anagen hair count of Figure 7 now indicates a 50:50 ratio again between anagen and telogen hairs. Thus, in this example, 4 of the 8 undamaged hairs described in (2) above would likely be anagen, resulting in a count of 4 anagen hairs compared to 6 at baseline. This corresponds to the observed long-term (permanent) efficacy of 33%. Thus, the mid-term (3-month) data underestimates the laser efficacy due to the natural hair growth cycle and the treatment cycle used for the device, and does not represent a true measure of the laser efficacy. The remainder of the data is unaffected by this artifact and accurately estimates the short-term and long-term laser efficacy. Similarly, if more than three treatments had been performed and the spacing between treatments was increased, the efficacy at 3 months following the final treatment would be expected to be substantially greater than that measured in the present study. The mode of action of the diode laser used in this study is thermal heating that results from the absorption of infrared light by melanin found in the hair shaft or hair bulb. Since dark hair contains more melanin than light hairs, one would anticipate a greater efficacy in the removal of darkercolored hairs than lighter-colored hairs following laser treatment. This was not the case in the present study. However, there are a number of factors that may counterbalance the presumed benefit of greater absorption by melanin in darker hairs and the anticipated better response. One of these factors is pain tolerance. Subjects were allowed to self select the power level setting of the device at each treatment visit. It is likely that treatment of darker hairs may result in more pain than treatment of lighter hairs since there is more melanin and a higher level of laser light absorption. This might, in turn, encourage subjects with darker hair color to use lower energy fluences that would reduce the pain but also decrease the response. Conversely, subjects with lighter-colored hair might tolerate higher energy fluences due to less melanin content in the hair, reducing absorption, and causing less discomfort. As the number of hairs in the treatment area diminished, subjects would likely be able to increase the power level setting at subsequent treatment visits without additional discomfort. In this way, pain may tend to equalize the efficacy in treating hairs of different colors and density since it can be anticipated that individuals will tend to operate the laser at a pain level that is tolerable for them. Although the sample size is too small for statistical significance, the data from the abdomen, chest and upper lip sites are consistent with the other sites, suggesting that these sites may have similar efficacy. While the literature fails to identify a lack of anatomic site specificity with physician-directed devices used for hair removal, there are new factors present in self-administered treatments. A few of the variables that might affect the results include the handedness of the user and the ability to physically reach or treat certain body locations. However, this device does appear to be effective on all of the studied body sites. CONCLUSION In a controlled clinical environment that simulates athome consumer use, the battery-powered, hand-held, portable diode laser used in this study demonstrated a high level of effectiveness in the removal of hair with minimal to no side effects for appropriate users. Even for the contraindicated users with Fitzpatrick Skin Types V and VI, the device showed only a low incidence of transient and mild side effects. The data also show that the package labeling provided an appropriate level of knowledge to permit safe and effective use of this device. Overall, the batterypowered, hand-held, portable diode laser has an excellent benefit-to-risk ratio and is suitable for at-home consumer use for the removal of unwanted or excess hair. REFERENCES 1. Wagner RF Jr., Tomich JM, Grande DJ. Electrolysis and thermolysis for permanent hair removal. J Am Acad Dermatol 1985;12(3): Wagner RF Jr. Medical and technical issues in office electrolysis and thermolysis. J Dermatol Surg Oncol 1993; 19(6): Anderson RR, Parrish JA. Selective photothermolysis: Precise microsurgery by selective absorption of pulsed radiation. Science 1983;220(4596): Grossman MC, Dierickx CC, Farinelli W, Flotte T, Anderson RR. Damage to hair follicles by normal-mode ruby laser pulses. 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Prospective study of hair reduction by diode laser (800 nm) with long-term follow-up. Dermatol Surg 2000;26(5): McCoy S, Evans A, James C. Long-pulsed ruby laser for permanent hair reduction: Histological analysis after 3,4 1/2, and 6 months. Lasers Surg Med 2002;30(5): Lorenz S, Brunnberg S, Landthaler M, Hohenleutner U. Hair removal with the long pulsed Nd:YAG laser: A prospective study with one year follow-up. Lasers Surg Med 2002;30(2): Liew SH. Laser hair removal: Guidelines for management. Am J Clin Dermatol 2002;3(2): Kolinko VG, Littler CM, Cole A. Influence of the anagen:telogen ratio on Q-switched Nd:YAG laser hair removal efficacy. Lasers Surg Med 2000;26(1):33 40.