Does High SPF offer better protection?

Does High SPF offer better protection? An analysis of the issue Darrell S. Rigel, MD MS Clinical Professor of Dermatology New York University Medical Center New York, New York Darrell S. Rigel, MD MS Does High SPF offer better protection? Disclosures: J and J A, H, I Beiersdorf C, H Other Cancers 1,584,500 Cancer USA - 2018 Skin Cancer 2,900,000 Skin Cancer USA - 2018 Melanoma 91,270 1645000 More Skin Cancers than all other cancers combined NMSC (BCC SCC) 3,000,000 Lifetime Risk Invasive MM 1/1500 1/600 1/250 Melanoma - USA 1/150 1/100 1/74 1/58 1/47 1/40 Projected Melanoma US 2018 Invasive = 91,270 In-situ = 87,290 1930 1950 1980 1985 1993 2000 2008 2018 2020 Rigel et al, NYU Melanoma Cooperative Group, 2018 1

Melanoma USA 2018 Lifetime Risk Invasive and Insitu MM 1/24 178, 560 total cases 1930 1950 1980 1985 1993 2000 2018 Rigel et al, NYU Melanoma Cooperative Group, 2018 Siegel et al, Ca J Clinicians, 2018 10000 9000 8000 7000 6000 5000 4000 3000 2000 1000 0 US Annual Deaths from Melanoma 9940 10130 9710 9730 9480 9180 9320 8450 8650 8700 8790 8110 7910 ACS 100% 80% 60% 40% 20% 0% 82% MM Survival US Trends over Time 88% 94% 1975-77 1987-89 2007-13 Siegel et al, CA J Clinicians, 2018 Skin Cancer Deaths US - 2018 Melanoma 9,320 Primary vs Secondary Prevention Primary = Protection Secondary = Early Detection Other 3,860 Over 1 American dies of Melanoma every hour Impact Incidence Impact Mortality 2

What can we conclude from this data? Secondary prevention efforts appear to be making an impact Primary prevention not as impactful Focus of our efforts on primary prevention behavioral change What Causes Melanoma? The overwhelming majority caused by UV exposure Melanoma vs. Latitude USA Hawaii Atlanta Seattle Connecticut Detroit Utah Los Angeles San Jose NM San Francisco Iowa SEER 2015 UV and Melanoma Risk Sunlight is the major environmental risk factor for melanoma Examine if S-shaped curves describe the relationship between solar UV doses and MM incidence and the % of MM that can be directly related to UV exposure Analysis indicates that S-shaped associations describe the data well (P < 0.0001). Conclusion: Between 89 and 95% of the annual CM cases are caused by solar UV exposure. Avoidance of UV radiation will reduce the incidence of MM. Juzeniene et al. Int J Hyg Environ Health. 2014 Are ALL melanomas caused by UV exposure? Sunburn, Skin Aging and Skin Cancer are Caused by Same Wavelengths of Sunlight Sensitivity No, but the vast majority are! UVB Wavelength (nm) UVA 1. ISO 17166/CIE S007/E. 2. de Gruijl FR, Van der Leun JC. Health Phys. 1994;67(4):319-325. 3. Kligman LH, Sayre RM. Photochem Photobiol. 1991;53(2):237-242. 3

Does Sunscreen Usage Lower Skin Cancer Risk? 33 Reduced melanoma risk after regular sunscreen use 1,621 randomly selected residents of Nambour (Queensland) Australia, age 25 to 75 years, were randomly assigned to daily or discretionary sunscreen application to head and arms Treated for 5 years then followed for 10 years Reduced melanoma risk after regular sunscreen use Green et al, J Clin Oncol, 2011 J Clin Oncol. 2011 Jan 20;29(3):257 63. doi: 10.1200/JCO.2010.28.7078. Epub 2010 Dec 6 Sunscreen Usage and Melanoma Risk All Melanomas Sunscreen Usage and Melanoma Risk Invasive MMs 1 1 1 1 0.75 0.75 Relative Risk 0.5 0.25 0.5 Relative Risk 0.5 0.25 0.27 0 0 Discretionary Daily Discretionary Daily 4

Reduced melanoma risk after regular sunscreen use 1,621 randomly selected residents of Nambour (Queensland) Australia, age 25 to 75 years, were randomly assigned to daily or discretionary sunscreen application to head and arms Treated for 5 years then followed for 10 years Only 11 new MMs in daily group vs. 22 (p=0.051) 2 Invasive MMs in daily group vs.11 Conclusions: Melanoma risk significantly lowered by regular sunscreen use in adults Green et al, J Clin Oncol, 2011 Skin cancers in Australia prevented by regular sunscreen use Estimated the proportion of skin cancers that would have occurred but were likely prevented by regular sunscreen use Regular sunscreen use prevented around 14,190 persons from developing SCCs (PF 9.3%) and 1,730 from Melanoma (PF 14%) Conclusions: Prevailing levels of sunscreen use probably reduced skin cancer incidence by 10-15% Sunscreen should be a component of a comprehensive sun protection strategy Olsen et al, Aust N Z J Public Health. 2015 How many melanomas might be prevented if more people applied sunscreen regularly? Calculated the PF, the proportional difference between the observed number of melanomas arising under prevailing levels of 5% annual increase in sunscreen use for 10 years (50% increase) How many melanomas might be prevented if more people applied sunscreen regularly? Calculated the PF, the proportional difference between the observed number of melanomas arising under prevailing levels of 5% annual increase in sunscreen use for 10 years (50% increase) Estimated that cumulatively to 2031, 231,053 fewer melanomas would arise in the U.S. white population (PF 11%) Olsen et al, Br J Dermatol, 2017 Olsen et al, Br J Dermatol, 2017 How many melanomas might be prevented if more people applied sunscreen regularly? How many melanomas might be prevented if more people applied sunscreen regularly? Calculated the PF, the proportional difference between the observed number of melanomas arising under prevailing levels of 5% annual increase in sunscreen use for 10 years (50% increase) Estimated that cumulatively to 2031, 231,053 fewer melanomas would arise in the U.S. white population (PF 11%) Conclusions: Interventions to increase use of sunscreen would result in reductions in melanoma incidence Countries with a high incidence of melanoma should monitor levels of sunscreen use British Journal of Dermatology 14 DEC 2017 DOI: 10.1111/bjd.16079 Olsen et al, Br J Dermatol, 2017 5

MM risk using SPF<15 vs SPF >15 Percentage improvement with regular use of SPF>15 Development of SPF 50% 40% 30% 20% 10% 21% 20% 33% Lowered risk of melanoma Correlation of indoor solar simulator with natural sunlight Natural sunlight effects could be duplicated with solar simulator 0% Blond/Red Hair Freckling in Sun Using SPF > 15 Norwegian Women Study N = 143,844 Ghiasvand et al, J Clin Oncol, 2016 Sayre et al, Arch Dermatol, 1978 How high is high enough? 54 6

No topical No topical No topical SPF 55 Delivered 0 1 MED 3 MED 55 MED UVR MEDs Theoretical 0 1 MED 3 MED 1 MED Equivalent 12 Subjects, phototype 1-3 Standard 2 mg/cm2 sunscreen application rate MED observations at 24 hours 3mm punch biopsies taken at 24 hours SPF 55 sunscreen contained: 5% octyl salicylate, 10% homosalate, 6% oxybenzone, 3% avobenzone, and 2.8 % octocrylene Photodermatol Photoimmunol Photomed. 2014 Aug;30(4):212 9. doi: 10.1111/phpp.12124. Epub 2014 May 27 Broad spectrum high-spf photostable sunscreen with high UVA-PF can protect against cellular damage at high UV levels To evaluate if high-spf sunscreen can protect skin at the cellular level under UV exposure doses [>50 MEDs] similarly to the SPF value Sunburn cells, Langerhans cells, thymine dimers, protein 53 (p53), and matrix metalloproteinase (MMP)-1 and MMP-9 endpoints were evaluated in biopsies from 12 subjects: unprotected exposed to 0, 1 and 3 MED SPF 55 protected exposed to 55 MED of UV radiation After 55 MEDs, sunscreen-protected sites showed either significantly less damage or no difference than the 1 MEDexposed unprotected sites Conclusions: High-SPF sunscreen with high UVA-PF can provide proportionately high protection against multiple cellular damage markers Cole et al, Photodermatol Photoimmunol Photomed. 2014 Sunscreen Use Not Only Protects, But Promotes Reversal of Photodamage Daily use of a facial photostable broad spectrum sunscreen (SPF 30) over one year significantly improves clinical evaluation of photoaging Manpreet Randhawa, PhD,* Steven Wang, MD, James J. Leyden, MD, Gabriela O. Cula, PhD,* Alessandra Pagnoni, MD,x and Michael D. Southall, PhD* Clinical evaluations showed all photoaging parameters improved significantly from baseline as early as week 1-2, and continued until week 52 Skin texture, clarity, and mottled/discrete pigmentation were most improved parameters Self-assessment showed significant improvement in skin clarity and texture 100 vs. 50 SPF levels vs. UVB absorption Marginal increase in UVB protection from SPF 50 to SPF 100 is only 1% 100% of subjects showed improvement in skin clarity and texture It s Not About How Much Is Blocked It s what gets through that counts against a lifetime of damage SPF 100 = Greater Sun Protection Over Lifetime: The Bucket Theory Moving from SPF 15 to 30 is only incremental 3.3% added protection Moving from SPF 30 to 50 is only 1.7% added protection 100 % Blocked Sunburning UVR 90 80 70 60 50 40 30 20 10 % Blocked 0 0 10 20 30 40 50 60 70 80 90 100 7

Shift Conversation to Cumulative Damage Patients Often Don t Apply Recommended Amounts of Sunscreen Although daily benefits of HIGH SPF are important, cumulative benefits over a lifetime can be life-saving Protection for a day at the beach against sunburn is one thing Protection over a lifetime against skin cancer and photoaging is a another critical consideration in sun safe behavior Average Size 4 6 Oz 100 vs. 50 SPF levels vs. UVB absorption with real world application But this assumes sunscreen applied at tested concentration (2mg/cm 2 ) Typically, 25 50% of rated amount applied Impact of under application of sunscreen SPF of sunscreens are tested using a thickness of 2 mg/cm 2 Investigations show that sunscreen under natural conditions is applied insufficiently with amounts about 0.39 to 1.0 mg/cm 2 Missing areas and UV radiation exposure before sunscreen application are other pitfalls that reduce the protective effect of sunscreens considerably Petersen et al, Photodermatol Photoimmunol Photomed. 2014 Patients Under Apply Sunscreen High SPF Compensates for Under Application of Sunscreen Numerous studies have shown that consumers typically under apply product by 1/4 to 1/2 of what should be applied Data shows that consumers seldom re-apply after the initial application Not all body areas get comprehensive application and coverage 71 OBJECTIVE: To measure the actual SPF values of various sunscreens (SPF 30 to 100) applied in the reduced amounts typically used by consumers Ouyang et al, J Am Acad Dermatol, 2012 8

High SPF Offers Meaningful Margin of Safety Journal of the American Academy of Dermatology. 2012;67(6):1220 1227. SPF protection is directly and linearly proportional to the application quantity Use of high-spf products can provide meaningful protection that low- SPF products may not when underapplied Ouyang et al, J Am Acad Dermatol, 2012 Methods 4 lotion and 2 spray sunscreens, selected based on formulation similarities (A) SPF 30 lotion sunscreen (B) SPF 100 lotion sunscreen (C) SPF 100 spray sunscreen (D) SPF 50 lotion sunscreen (E) SPF 50 spray sunscreen (F) SPF 70 lotion sunscreen Ouyang et al, J Am Acad Dermatol, 2012 Methods Application densities: 0.5, 1.0, 1.5 and 2.0 mg/cm 2 Products applied according to the standard protocol for SPF Testing, on the back of human volunteers Ouyang et al, J Am Acad Dermatol, 2012 Actual SPF at different application doses Mean SPF at A Label SPF: 30 D Label SPF: 50+ F Label SPF: 70+ B Label SPF: E Label SPF: 100 50 spray C Label SPF: 100 spray 2 mg/cm 2 31.0 52.8 70.6 104.6 50.7 105.3 Mean SPF at 1.5 mg/cm 2 21.8 41.3 54.4 79.3 38.6 75.0 Mean SPF at 1 mg/cm 2 16.0 26.0 37.1 55.9 25.7 50.1 Mean SPF at 0.5 mg/cm 2 8.8 13.9 19.3 27.1 12.6 22.4 Ouyang et al, J Am Acad Dermatol, 2012 Results There was a linear relationship between application density and the actual SPF Sunscreens labeled SPF > 50 provided significant protection even when applied at real world typical application densities SPF 50+ Status Sunscreens with SPF of 50 or more are available in some other developed countries, including New Zealand, the US and many European countries Australia and other countries have an SPF 50+ cap Ouyang et al, J Am Acad Dermatol, 2012 9

SPF Cap 50+? SPF Cap 50+? Higher SPFs have better protection at real world application concentrations 50+ Is it 51 or 100? Higher SPFs have better protection at real world application concentrations 50+ Is it 51 or 100? What will be the incentive to develop a better sunscreen if there is no way to reflect that on the label? High SPF is Durable in Real World Use Realistic sunscreen durability A randomized, double-blinded, controlled clinical study H. Ouyang; K. Meyer; P. Maitra; S. Daly; A. Farberg; D. Rigel, MD Evaluation of SPF 70 sunscreen over 8 hours with exercise and 80 minutes of water exposure Reapplication of SPF products is critical to compensate for missed spots, under-application or rub-off; however, many people do not follow recommendations to reapply every 2 hours Which is better? Shade? High SPF Sunscreen? Higher SPF sunscreens may provide an additional margin of safety for people who do not reapply as recommended After 8 hours + 80 min water exposure, SPF at 64.3 Journal of the American Academy of Dermatology, Volume 74, Issue 5, AB228 82 83 Objective: To directly measure sunburn protection offered by shade from a beach umbrella in comparison to a high SPF sunscreen Methods Randomized, Evaluator blinded, Controlled Study Lakeside Beach near Dallas Texas, August 12 75 90 degrees F Horizontal UV Intensity 3 5 MEDs/hour 81 Participants Sunscreen ONLY Group (SPF 100) Shade ONLY Group (beach umbrella) Ou Yang et al, JAMA Dermatol, 2017 10

Methods Methods SUNSCREEN Group SHADE Group Neutrogena Ultra Sheer SPF 100 Instructed to apply following label directions Sit at beach (no water activity) for 3.5 hours Reminded to reapply after 2 hours Standard beach umbrella Round, 80 diameter, 75 height UPF rating 1000+ Sit under umbrella shade at beach for 3.5 hours Not allowed to use sunscreen Reminded to reposition as solar angle changed Ou Yang et al, JAMA Dermatol, 2017 Ou Yang et al, JAMA Dermatol, 2017 Evaluation Methods 24 hours after beach sun exposure 7 body sites evaluated (evaluator blinded to group) face, upper chest, back of neck, left/right arm, left/right leg Clinical Evaluation 0 = no sunburn 1 = possible sunburn, not clearly defined 2 = defined redness 3 = severe sunburn, pronounced redness 4 = edema, blisters Compared scores to baseline (baseline = 0 = NO evidence of sunburn at start study) Ou Yang et al, JAMA Dermatol, 2017 0.3 0.2 0.1 0 Face Upper Chest Back of Neck Results SUNSCREEN ONLY Average Sunburn Score Right Arm Left Arm Right Leg Left Leg Sunscreen group had significant increase (p<0.05) in sunburn for face only Ou Yang et al, JAMA Dermatol, 2017 Results Conclusions 1 0.75 0.5 SHADE ONLY Average Sunburn Score Seeking shade alone may not provide sufficient protection for extended sun UV exposure Shade Protection Factor: challenging to quantify given multiple factors 0.25 0 Face Upper Chest Back of Neck Right Arm Left Arm Right Leg Left Leg Shade group had significant increase (p<0.001) in sunburn for all body sites Ou Yang et al, JAMA Dermatol, 2017 Ou Yang et al, JAMA Dermatol, 2017 11

Does higher SPF protect significantly better in real world settings? 98 High SPF formulation more effective during intense UV exposures SPF 85 formulation tested vs. SPF 50 56 subjects applied sunscreen to face while skiing at Vail, Colorado 1/13/08 1 application only at start of day Average hours exposed 5.0 hours Noon Sun 22 minutes = 1 MED 7/28 sunburned SPF 50 vs. 1/28 SPF 85 (p=0.02) Conclusion: SPF 85 formulation more effective than SPF 50 in protecting from sunburn with a single application in a high UV test environment Russak et al, JAAD 2010 Sunscreen Proposed Rule on SPFs Proposing to limit SPF to 50+ Acknowledged that SPFs higher than 50 have been substantiated and results are validated and repeatable Additional data demonstrating additional clinical benefit above SPF 50 are being collected by the FDA Sunscreens labeled with SPFs above 50 may remain on the market until this proposed rule becomes final, provided they follow the appropriate SPF test. Depending on how this proposed rule is finalized, these products may/may not be able to continue on the market. For each subject: 1. How much sunscreen was used? 2. How much time did each individual subject spend in the sun? 3. Were there reapplications (not allowed in study)? 12

In vivo comparison of SPF 100 vs 50 in Actual Use Conditions 104 BACKGROUND In the 2011 proposed monograph, the US Food and Drug Administration requested additional data stating there is currently insufficient evidence that there is clinical benefit to the consumer at SPF above 50. In real world settings, consumers apply sunscreens at densities lower than are used to clinically determine SPF and the linear dependence of SPF to application density is well established. BACKGROUND In the 2011 proposed monograph, the US Food and Drug Administration requested additional data stating there is currently insufficient evidence that there is clinical benefit to the consumer at SPF above 50. In real world settings, consumers apply sunscreens at densities lower than are used to clinically determine SPF and the linear dependence of SPF to application density is well established. It is hypothesized that a sunscreen with a higher SPF would provide greater in use efficacy compared with one currently labeled at the proposed maximum of SPF 50+. Objective of this study was to evaluate the difference in sunburn protection provided by different SPF sunscreens during a day of downhill snow skiing. METHODS 199 healthy men and women 18 years of age participated in a one day split face, randomized, double blind study in Vail, Colorado. The difference in sunburn protection provided by two currently available sunscreens (SPF 50+ and SPF 100+) was evaluated. Products were supplied in a kit containing two overwrapped tubes of sunscreen marked right and left. Each subject wore both sunscreens simultaneously, with product application randomized to either the right or left side of the face. Subjects utilized the sunscreens as they would normally during ski activities. Diaries were used to record sun exposure time and the frequency and timing of sunscreen re applications. Subjects reported the next morning for clinical evaluation. STUDY DESIGN Participants and evaluator were blinded to test product identity. Participants (Fitzpatrick skin type I to III, Erythema Score of 0.5 or less) were randomized to one of two treatment regimens for the face and neck: (SPF 50+ on left & SPF 100+ on right) or (SPF 100+ on left & SPF 50+ on right) Products Evaluated Neutrogena Ultra Sheer Dry Touch Sunscreen Lotion Broad Spectrum SPF 100+ (UPC 086800873105) Banana Boat Sport Performance with Powerstay Technology Sunscreen Lotion Broad Spectrum SPF 50+ (UPC 079656045130) 13

STUDY DESIGN STUDY DESIGN Participants self applied the pre weighed study products upon receipt, prior to outdoor sun exposure as they normally would. To address any questions by subjects about product application or usage, subjects were referred to the product study labels which contained the complete sunscreen Drug Facts information without ingredients list. Time spent outdoors was captured by the subjects in the provided exposure diary and solar conditions were tracked utilizing a stationary radiometer. An application diary was used to record the frequency and time of any product reapplications. Primary and Secondary efficacy endpoints were evaluated by clinical grading the morning after the recreational sun exposure period. At which time study products were also collected and weighed to determine usage. STUDY PARTICIPATION AND CONDITIONS Conducted on a sunny day (March 21 st, 2016) during normal recreational skiing/snowboarding in Vail, Colorado, USA (base elevation approx. 8,200 ). 199 participants (42% women, 37±16 years old); Fitzpatrick skin Type I (16%), Type II (73%), & Type III (11%) Participants averaged 6.05 ± 1.29 hours of sun exposure STUDY PARTICIPATION AND CONDITIONS Daily solar conditions tracked: Direct UVA and UVB metered 10:00 am to 4:30 pm local time Average cumulative un weighted subject UV exposure doses* 54.893 J/cm 2 UVA 1.009 J/cm 2 UVB Denotes diffuse cloud cover 25+ MEDs for Type II Skin *UV exposure calculated from pairing of radiometry data averaged at half hourly intervals with diary reported subject exposure time and duration. 10:00 am 12:00 pm 2:00 pm 4:00 pm RESULTS Primary Endpoint RESULTS Primary Endpoint Percentage of subjects (n = 199) 55.3% P <.001 39.7% 5.0% SPF 50 side of face 11x more likely to be sunburned than SPF 100 side More sunburned on SPF 50+ side No difference More sunburned on SPF 100+ side 14

RESULTS Secondary Endpoint Erythema was significantly lower on the SPF 100+ protected side of the face, and erythema progression was observed to be more than twice as severe on the SPF 50+ protected side RESULTS Usage No differences were observed in usage, application density, or reapplication frequency of the study products 1.10 mg/cm 2 1.04 mg/cm 2 Average Product Application Density RESULTS Post Hoc Analysis The number of sunscreen reapplications was not observed to diminish the enhanced protection benefit of the SPF 100+ product RESULTS Post Hoc Analysis SPF 100+ sunscreen was significantly more effective at protecting against sunburn in all examined skin types CONCLUSIONS The SPF 100+ sunscreen was significantly more effective in protecting against sunburn than the SPF 50+ sunscreen for all skin types evaluated These findings demonstrate that there is a need for sunscreens labelled with SPFs greater than 50+ to provide consumers with better choices for sunburn protection New measures of measuring sunscreen effectiveness Williams et al, JAMA Dermatol, Submitted 125 15

A new approach for evaluating the water resistance of sunscreens: Tap water vs. Salt water vs. Chlorine water In-vivo screening approach to measure water resistance using UVA-induced fluorescence imaging All testing performed on the forearms of 10 subjects using UVA fluorescence imaging with tap, salt and chlorinated water. Method effective and also tests water specific sunscreens such as a beach dedicated product showing a 20% higher resistance to salt water versus tap and chlorine waters Conclusion: The use of UVA-induced fluorescence imaging on skin proved a useful in-vivo approach for measuring the water resistance performance Puccetti et al, Int J Cosmet Sci, 2014 New non-invasive approach assessing in vivo SPF using Diffuse Reflectance Spectroscopy and in vitro transmission Seventeen test materials with known in vivo SPF values were tested Combines the evaluation of UVA absorption spectrum as measured by diffuse reflectance spectroscopy (DRS) with the spectral absorbance "shape" of the UVB absorbance of test material as determined with in-vitro thin film spectroscopy Strong correlation of this new method with in vivo clinical SPF values r 2 = 0.98 Conclusion: This methodology provides a new approach to determine SPF values without the extensive UV irradiation procedures (and biological responses) currently used to establish sunscreen efficacy Ruvolo et al, Photodermatol Photoimmunol Photomed, 2014 Immune Protection Factor of Sunscreens UV exposure leads to decreased immune response in skin UV induced suppression of Nickel allergy measure in subjects wearing sunscreen IPFs derived from the ratio of the minimal immune suppression dose (MISD) of UV in sunscreen applied sites vs. MISD of unprotected sites Conclusions: IPF can be used as a measure of UV protection Accumulated p53 protein and UVA Protection Levels in Sunscreen 2 sunscreens (SPF 7 PFA 3 or 7) tested p53 levels measured in biopsies from UVA exposed skin Increased p53 with same exposure levels with lower UVA protection Conclusions: p53 levels could be a biologic measure of UVA protection Damian et al, Photochem Photobiol, 1999 Seite et al, Photoderm Photoimmunol Photomed, 2000 Chemiluminescence Evidence of Free Radical Generation Free Radical Generation After 20 J/cm 2 UVA Irradiation Intensity (cps) Unirradiated 700 600 500 400 Baseline Non-photostable Sunscreen Untreated Photostable 300 Sunscreen 200 100 0 0 50 100 150 200 250 300 Time (s) Chu M, Bargo P, Cole CA. Measurement of the reduction of UVA-induced oxidative stress after application of photostable sunscreens. 2004 Radical Sun Protection Factor - RSF Free radical formation from UV exposure in the skin measured in pig skin biopsies with electron spin resonance spectrometry Correlated with in-vivo measurements in human skin The effectiveness of UV filters inversely correlate with level of radical generation Conclusions: Biophysical endpoint of free radical and reactive oxygen species in skin (RSF) can measure UV protection in sunscreens Herrling et al, Spetrochim Acta A Mol Biomol Spectrosc, 2006 16

DNA Dosimetry Assessment for Sunscreen Genotoxic Photoprotection Sun Protection Factor for DNA (DNA-SPF) is calculated by using specific DNA repair enzymes, and it is defined as the capacity for inhibiting the generation of cyclobutane pyrimidine dimers (CPD) and oxidised DNA bases compared with unprotected control samples 5 commercial sunscreens and 17 sun protection formulations were tested All of the commercial brands of SPF 30 sunscreens provided sufficient protection against simulated sunlight genotoxicity Conclusions: DNA dosimeter is an alternative, complementary, and reliable method for the quantification of sunscreen photoprotection at the level of DNA damage Schuch et al, PLoS One, 2012 Integrated Sun Protection Factor - IPF Free radical formation occurs from UV, IR-A and visible light exposure in the skin Measured in skin biopsies with electron spin resonance X-band spectrometry Integrates radiation exposure effects in all skin layers Conclusions: Method effective for testing overall UV protection Zastrow et al, Skin Pharmacol Physiol, 2004 Dermatologists Perceptions Recommendations and Usage of Sunscreen Dermatologists' Views 100% 100% 99% 99% 90% 97% 80% What do our colleagues think? 70% 60% 50% 40% 30% 20% 10% 0% Lowers SkCA Risk Reduces photoaging Rec to friends/family Pts use too little 134 N = 156 Farberg et al, JAMA Dermatol. 2016 Dermatologists Perceptions Recommendations and Usage of Sunscreen Dermatologists' Beliefs 100% 90% 96% 97% 91% 87% 80% 83% 70% 60% 50% Dermatologists Perceptions Recommendations and Usage of Sunscreen Dermatologists' Recommendation Factors 100% 99% 90% 96% 80% 70% 71% 60% 50% 40% 30% 20% 10% 40% 30% 20% 10% 42% 0% Sunscreens safe Oxybenzone safe Retinyl palmitate safe N = 156 High SPFs safety Recommend margin SPF50+ Farberg et al, JAMA Dermatol. 2016 0% SPF level Broad spectrum Feel/elegance Photostability N = 156 Farberg et al, JAMA Dermatol. 2016 17

100% More SPF Years Recommendation in Practice, More Likely By Years to Recommend in Practice High SPF 80% 60% 8% 12% 6% 7% 8% 10% 16% 16% 15% 11% 23% Despite Decades of Science, Education, Sunscreen Compliance is Low Only 30% of women and >15% of men use sunscreen on face and exposed skin 1 40% 20% 72% 88% 79% 72% 73% 63% Only 39.1% of American households purchase sunscreen 2 0% 4% 4% 4% 4% 4% Overall 0 5 years 5 10 years 10 20 years 20 30 years 30+ years SPF 70+ SPF 50 69 SPF 30 49 SPF 15 29 SPF <15 1 American Academy of Dermatology survey, May 2015 2 Source: IRI, US Sunscreen Household Penetration, 52 weeks ending 6/29/2014, all major retail outlets High SPF is proven to offer clinically significant benefits in real-world settings and actual use scenarios Discuss value of High SPF sunscreens for: patients who under-apply acute and long-term exposure extended outdoor activity Summary Photoprotection important and lowers Skin Cancer risk Higher SPFs have been proven to have clinical benefits to users Measures of UVA protection better but still not optimal Dermatologists are recommending higher SPFs Measures of protection are evolving in future with new approaches coming Have to improve getting the message to our pts 18