Regulatory and HTA Considerations for Development of Real-World Data Derived External Controls.

Regulators and Health Technology Assessment (HTA) bodies are increasingly familiar with, and publishing guidance on, external controls derived from real-world data (RWD) to generate real-world evidence (RWE). We recently conducted a systematic literature review (SLR) evaluating publicly available information on the use of RWD-derived external controls to contextualize outcomes from uncontrolled trials submitted to the European Medicines Agency (EMA), the US Food and Drug Administration (FDA), and/or select HTA bodies. The review identified several key operational and methodological aspects for which more detailed guidance and alignment within and between regulatory agencies and HTA bodies is necessary. This paper builds on the SLR findings by delineating a set of key takeaways for the responsible generation of fit-for-purpose RWE. Practical methodological and operational guidelines for designing, conducting, and reporting RWD-derived external control studies are explored and discussed. These considerations include: (i) early engagement with regulators and HTA bodies during the study planning phase; (ii) consideration of the appropriateness and comparability of external controls across multiple dimensions, including eligibility criteria, temporality, population representation, and clinical evaluation; (iii) ensuring adequate sample sizes, including hypothesis testing considerations; (iv) implementation of a clear and transparent strategy for assessing and addressing data quality, including data missingness across trials and RWD; (v) selection of comparable and meaningful endpoints that are operationalized and analyzed using appropriate analytic methods; and (vi) conduct of sensitivity analyses to assess the robustness of findings in the context of uncertainty and sources of potential bias.

Effectively Leveraging RWD for External Controls: A Systematic Literature Review of Regulatory and HTA Decisions.

Real-world data (RWD)-derived external controls can be used to contextualize efficacy findings for investigational therapies evaluated in uncontrolled trials. As the number of submissions to regulatory and health technology assessment (HTA) bodies using external controls rises, and in light of recent regulatory and HTA guidance on the appropriate use of RWD, there is a need to address the operational and methodological challenges impeding the quality of real-world evidence (RWE) generation and the consistency in evaluation of RWE across agencies. This systematic review summarizes publicly available information on the use of external controls to contextualize outcomes from uncontrolled trials for all indications from January 1, 2015, through August 20, 2021, that were submitted to the European Medicines Agency, the US Food and Drug Administration, and/or select major HTA bodies (National Institute for Health and Care Excellence (NICE), Haute Autorité de Santé (HAS), Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG), and Gemeinsamer Bundesausschuss (G-BA)). By systematically reviewing submissions to regulatory and HTA bodies in the context of recent guidance, this study provides quantitative and qualitative insights into how external control design and analytic choices may be viewed by different agencies in practice. The primary operational and methodological aspects identified for discussion include, but are not limited to, engagement of regulators and HTA bodies, approaches to handling missing data (a component of data quality), and selection of real-world endpoints. Continued collaboration and guidance to address these and other aspects will inform and assist stakeholders attempting to generate evidence using external controls.

Assessing the incidence of osteosarcoma among teriparatide-treated patients using linkage of commercial pharmacy and state cancer registry data, contributing to the removal of boxed warning and other labeling changes.

BACKGROUND: Teriparatide, a recombinant human parathyroid hormone analogue, is associated with increased bone mineral density and a decreased risk of fractures. A dose-dependent increase in the incidence of osteosarcoma was observed in toxicology studies conducted in rats. The primary objective of this study was to estimate the incidence of osteosarcoma over a 10-year period among teriparatide-treated patients versus patients unexposed to teriparatide with osteoporosis and patients in the general population using national pharmacy dispensing data linked with data from participating state cancer registries (SCRs) in the US. METHODS: Patients aged 18 years or older with a dispensed teriparatide prescription formed two different cohorts: Teriparatide-Osteoporosis (Teriparatide-OP) was formed by matching teriparatide patients to unexposed patients with osteoporosis and Teriparatide-General Population (Teriparatide-GP) was formed by matching teriparatide patients to general population patients with a dispensed prescription for a medication other than teriparatide. Matching was performed using select demographics and other variables. Study cohorts were linked to SCR data to ascertain osteosarcoma status. To account for missing outcome data from non-participating SCRs, two analytic approaches were used: the first adjusted the person-time at-risk using a coverage fraction and the second restricted the analyses to patients from states with participating SCRs. RESULTS: There were 18 osteosarcoma cases across four study cohorts: the same three cases in the Teriparatide-OP and Teriparatide-GP cohorts, six cases in the Osteoporosis cohort, and nine cases in the General Population cohort. For the analysis using the coverage fraction the incidence rate ratio (IRR) comparing the Teriparatide-OP and Teriparatide-GP cohorts to the Osteoporosis and General Population cohorts was 1.0 (95% CI: 0.2, 4.5) and 1.3 (95% CI: 0.2, 5.1), respectively. When restricting the analysis to patients from states with participating SCRs, the IRR was 0.6 (95% CI: 0.1, 3.6) and 0.8 (95% CI 0.1, 4.0), respectively. CONCLUSION: The estimates of association between teriparatide and osteosarcoma were imprecise due to the small number of observed osteosarcoma cases. However, the incidence of osteosarcoma observed in each study cohort was within the expected range given background rates for the US general population. The evidence generated by this study, in conjunction with other real-world studies evaluating the risk of osteosarcoma, was used to support changes to the US teriparatide label (including removal of the black box warning regarding potential risk of osteosarcoma) and expand treatment options for patients with osteoporosis.

Real-world cohort study of adult and pediatric patients treated for hereditary angioedema in the United States.

Background: There is limited real-world evidence on hereditary angioedema (HAE) patient characteristics and health-care resource utilization (HCRU); in addition, pediatric patients have been described in small cohorts. Objective: To describe patient characteristics, treatment patterns, and HCRU among adult and pediatric patients treated for HAE in a large U.S. cohort. Methods: This retrospective cohort study used an administrative claims data base (January 2006 to September 2015). Eligible patients with either ≥1 pharmacy claim for HAE-indicated therapies (C1 inhibitors, ecallantide, icatibant) or ≥2 medical claims with codes associated with HAE (per medical billing codes), and ≥1 claim for androgens, fresh frozen plasma, tranexamic acid, or ε-aminocaproic acid formed a "treated cohort." Three nonexclusive treated cohorts were assessed: overall, pediatric, and HCRU (≥2 years of continuous enrollment during 2010-2015). Results: Overall, 1429 patients received treatment (mean ± standard deviation [SD] age, 38.8 ±15.7 years; 62.4% female patients; mean ± SD Charlson Comorbidity Index of 1.4 ± 2.4). Common comorbidities were allergy or anaphylaxis (51.4%) and anxiety or depression (35.8%). Diagnoses indicative of HAE attacks included swelling and/or angioedema (78.5%), abdominal pain (55.6%), and asphyxiation (27.2%). Use of HAE-indicated medication rose between 2006 and 2015 to 81.8%, whereas androgen use declined (from 91.5% to 24.9%). Similar trends were observed in the pediatric treated cohort (n = 143). In the HCRU treated cohort (n = 538), HAE-related claims for emergency department and inpatient admissions were observed for 36.6% and 22.3% of patients, respectively. Conclusion: In a large U.S. cohort of adult and pediatric patients who received treatments indicated or used for HAE, common comorbidities and trends in resource use denoted the substantial burden of attacks, which reflected a continued need that recently approved long-term prophylactic treatments may help to address.

Awareness of, and Compliance with, Domperidone Revised Labeling After a Risk-Minimization Activity in Europe.

BACKGROUND AND OBJECTIVE: Risk-minimization measures (RMM), including label revisions were implemented in Europe for domperidone because of evidence of increased incidence of cardiac arrhythmia and sudden cardiac death. In accordance with the guideline on good pharmacovigilance practices, the European Medicines Agency Pharmacovigilance Risk Assessment Committee requested to conduct two studies to evaluate the effectiveness of these risk minimization measures. METHODS: In Belgium, France, Germany, Spain, and the UK, surveys were conducted to assess physicians' knowledge on the updated domperidone labeling information, and a drug-utilization study (DUS) was conducted using healthcare databases to assess domperidone prescribing patterns before and after the RMM. Four DUS sensitivity analyses (scenarios) evaluated uncertainty regarding domperidone treatment duration and indication. RESULTS: Among 1805 physicians participating in the survey, most were aware of the approved indication (nausea and vomiting, 80%), treatment duration (≤ 7 days, 70%), and maximum adult daily dose (10 mg three times daily, 84%). Only 33% selected the on-label indication from a list of indications for which they would prescribe domperidone. Awareness was low for medications contraindicated for concomitant use (26%) and contraindicated conditions (4%). In the DUS, under the optimistic scenario, a large improvement in labeling compliance from pre- to post-implementation period was observed in France (27% vs. 69%), while Belgium, Germany, Spain, and the UK showed small improvements (< 10%). In the other scenarios, there was little to no improvement in compliance with the revised labeling from the pre- to post-implementation periods in most countries. CONCLUSIONS: The survey findings documented that most physicians in all five countries were aware of the main aspects of the revised labeling. Results of the DUS were inconclusive regarding the effect of the RMM and compliance with the revised labeling for all countries except France.

Validating an algorithm for multiple myeloma based on administrative data using a SEER tumor registry and medical record review.

PURPOSE: Large numbers of multiple myeloma patients can be studied in real-world clinical settings using administrative databases. The validity of these studies is contingent upon accurate case identification. Our objective was to develop and evaluate algorithms to use with administrative data to identify multiple myeloma cases. METHODS: Patients aged ≥18 years with ≥1 International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code for multiple myeloma (203.0x) were identified at two study sites. At site 1, several algorithms were developed and validated by comparing results to tumor registry cases. An algorithm with a reasonable positive predictive value (PPV) (0.81) and sensitivity (0.73) was selected and then validated at site 2 where results were compared with medical chart data. The algorithm required that ICD-9-CM codes 203.0x occur before and after the diagnostic procedure codes for multiple myeloma. RESULTS: At site 1, we identified 1432 patients. The PPVs of algorithms tested ranged from 0.54 to 0.88. Sensitivities ranged from 0.30 to 0.88. At site 2, a random sample (n = 400) was selected from 3866 patients, and medical charts were reviewed by a clinician for 105 patients. Algorithm PPV was 0.86 (95% CI, 0.79-0.92). CONCLUSIONS: We identified cases of multiple myeloma with adequate validity for claims database analyses. At least two ICD-9-CM diagnosis codes 203.0x preceding diagnostic procedure codes for multiple myeloma followed by ICD-9-CM codes within a specific time window after diagnostic procedure codes were required to achieve reasonable algorithm performance.

Treatment patterns, adherence, and persistence among psoriasis patients treated with biologics in a real-world setting, overall and by disease severity.

PURPOSE: Describe treatment patterns by disease severity among biologic-treated psoriasis patients. MATERIALS AND METHODS: We selected our study cohort in the IQVIA PharMetrics Plus adjudicated claims database linked to Electronic Health Record data from Modernizing Medicine Data Services. Patients were classified as having mild, moderate, or severe psoriasis based on a hierarchy of available severity measures. Patients were followed for 360 days to assess combination therapy, therapy switching and restarting, adherence and persistence. RESULTS: The cohort comprised 2130 biologic-treated patients (mean age: 47.6 years; 45.4% female); 447 (21%) had available disease severity measures. Compared to patients with mild (N = 282) psoriasis, more patients with moderate (N = 116) or severe (N = 49) disease used combination therapy (21.3% vs. 34.5% and 32.7%, respectively), switched therapies (12.1% vs. 19.8% and 22.4%), and discontinued biologics (18.4% vs. 27.6% and 36.7%). Mean adherence was <75% by Medication Possession Ratio (MPR) (73.9%) and Proportion of Days Covered (PDC) (70.2%). Overall, 52.2% had a mean MPR >80%. Mean persistence to biologics was 297.6 days. Persistence and adherence decreased with increasing disease severity. CONCLUSIONS: Biologic-treated psoriasis patients had inadequate adherence (i.e., MPR <80%) and modest persistence to biologics, with moderate and severe patients demonstrating lower adherence and persistence than mild patients.

Healthcare resource utilization and costs among psoriasis patients treated with biologics, overall and by disease severity.

AIMS: To describe healthcare resource utilization (HCRU) and costs among biologic-treated psoriasis patients in the US, overall and by disease severity. MATERIALS AND METHODS: IQVIA PharMetrics Plus administrative claims data were linked with Modernizing Medicine Data Services Electronic Health Record data and used to select adult psoriasis patients between April 1, 2010 and December 31, 2014. Eligible patients were classified by disease severity (mild, moderate, severe) using a hierarchy of available clinical measures. One-year outcomes included all-cause and psoriasis-related outpatient, emergency department, inpatient, and pharmacy HCRU and costs. RESULTS: This study identified 2,130 biologic-treated psoriasis patients: 282 (13%) had mild, 116 (5%) moderate, and 49 (2%) severe disease; 1,683 (79%) could not be classified. The mean age was 47.6 years; 45.4% were female. Relative to mild psoriasis patients, patients with moderate or severe disease had more median all-cause outpatient encounters (28.0 [mild] vs 32.0 [moderate], 36.0 [severe]), more median psoriasis-related outpatient encounters (6.0 [mild] vs 7.5 [moderate], 8.0 [severe]), and a higher proportion of overall claims for medications that were psoriasis-related (28% [mild] vs 37% [moderate], 34% [severe]). Relative to mild psoriasis patients, patients with moderate or severe disease had higher median all-cause total costs ($37.7k [mild] vs $42.3k [moderate], $49.3k [severe]), higher median psoriasis-related total costs ($32.7k [mild] vs $34.9k [moderate], $40.5k [severe]), higher median all-cause pharmacy costs ($33.9k [mild] vs $36.5k [moderate], $36.4k [severe]), and higher median psoriasis-related pharmacy costs ($32.2k [mild] vs $33.9k [moderate], $35.6k [severe]). LIMITATIONS: The assessment of psoriasis disease severity may not have necessarily coincided with the timing of biologic use. The definition of disease severity prevented the assessment of temporality, and may have introduced selection bias. CONCLUSIONS: Biologic-treated patients with moderate or severe psoriasis cost the healthcare system more than patients with mild psoriasis, primarily driven by higher pharmacy costs and more outpatient encounters.

Melanoma Thickness and Survival Trends in the United States, 1989 to 2009.

BACKGROUND: With melanoma incidence rising and mortality stable, some question whether the melanoma epidemic is real. Melanoma thickness and survival trends may provide insights, but previous studies have been limited because of missing data on thickness. METHODS: With a validated imputation method for missing thickness data, we characterized melanoma thickness and survival trends among men and women in the Surveillance, Epidemiology, and End Results (SEER)-9 registries between 1989 and 2009. A total of 98,498 cases of invasive melanoma were identified. All statistical tests were two-sided. RESULTS: Incidence per 100 000 person-years increased (13.94, 95% confidence interval [CI] = 13.65 to 14.23, to 21.87, 95% CI = 21.56 to 22.19, P < .001) between 1989 to 1991 and 2007 to 2009, fatal incidence remained stable (2.32, 95% CI = 2.2 to 2.4, to 2.08, 95% CI = 2.0 to 2.2, P = .20) between 1989 to 1991 and 1998 to 2000, and five-year survival increased (88.29%, 95% CI = 87.60% to 88.95%, to 91.68%, 95% CI = 91.22% to 92.12%, P < .001) between 1989 to 1991 and 2001 to 2003. Increase in incidence occurred across all thickness groups. Median thickness decreased (0.73 to 0.58mm). Geometric mean thickness decreased (0.77 to 0.65mm) 4.6% (95% CI = 4.2% to 5.0%) every three years in multivariable analysis. Thickness decreased among T1/T2 tumors (0.01-1.00 and 1.01-2.00mm) and among all age and sex groups, whites, non-Hispanics, and all body sites. However, thickness increased among T3/T4 tumors (2.01-4.00 and > 4.00mm) and nodular melanomas; acral lentiginous melanomas approached statistical significance. Thickness remained unchanged among some racial minorities. Melanoma-specific survival improved (hazard ratio [HR] = 0.89, 95% CI = 0.88 to 0.91) every three years in multivariable analysis. Improvements in survival occurred across all subgroups except nonblack minorities, and nodular and acral lentiginous subtypes. CONCLUSIONS: Increasing incidence across all thickness groups coupled with T3/T4 lesions becoming thicker suggests that the melanoma epidemic is real and not simply an artifact of increased detection pressure of earlier-stage T1/T2 lesions. Survival is generally improving independent of thickness, but improvements in survival have not been experienced by certain minorities, and nodular and acral lentiginous subtypes.

Tanning and beauty: Mother and teenage daughters in discussion.

Tanning increases dramatically through the teenage years, but the family context of this health risk behavior is relatively unstudied. We conducted videotaped conversations between teenage girls (10th and 11th grade) and their mothers. We developed a coding system for discussion content and highlight findings including inadequate knowledge concerning the harms of tanning and positive views of outdoor tanning over indoor tanning, yet agreement that all tans are attractive. Many teens believed that indoor tanning is sometimes necessary to achieve the tanned look. These findings can usefully guide intervention development regarding the harms of all tanning, rather than indoor or outdoor tanning specifically.

Sunburn, sun exposure, and sun sensitivity in the Study of Nevi in Children.

PURPOSE: To examine the joint effect of sun exposure and sunburn on nevus counts (on the natural logarithm scale; log nevi) and the role of sun sensitivity. METHODS: We describe an analysis of cross-sectional data from 443 children enrolled in the prospective Study of Nevi in Children. To evaluate the joint effect, we partitioned the sum of squares because of interaction between sunburn and sun exposure into orthogonal components representing (1) monotonic increase in log nevi with increasing sun exposure (rate of increase of log nevi depends on sunburn), and (2) nonmonotonic pattern. RESULTS: In unadjusted analyses, there was a marginally significant monotonic pattern of interaction (P = .08). In adjusted analyses, sun exposure was associated with higher log nevi among those without sunburn (P < .001), but not among those with sunburn (P = .14). Sunburn was independently associated with log nevi (P = .02), even though sun sensitivity explained 29% (95% confidence interval: 2%-56%, P = .04) of its effect. Children with high sun sensitivity and sunburn had more nevi, regardless of sun exposure. CONCLUSIONS: A program of increasing sun protection in early childhood as a strategy for reducing nevi, when applied to the general population, may not equally benefit everyone.

Dermatoscopic imaging of skin lesions by high school students: a cross-sectional pilot study.

BACKGROUND: The ability of novices to perform imaging of skin lesions is not well studied. OBJECTIVES: To determine the ability of 12th grade high school students without formal training to take clinical and dermatoscopic images of skin lesions on patient-actors. PATIENTS/METHODS: Nineteen participants were divided into 11 gender-specific groups of 1-2 students. Groups were provided written instructions and assessed in their ability to (a) identify 8 pre-specified skin lesions, (b) take overview clinical images, and (c) take contact, polarized dermatoscopic images. Groups captured the same images twice using two different cameras [Nikon TM 1 J1 / VEOS HD1 and a VEOS DS3 (Canfield Scientific, Inc.)]. The sequence of camera use was determined using block randomization. If students made visibly poor skin contact during dermatoscopic imaging using their first camera, study investigators provided verbal instructions to place the second camera directly onto the skin. Students completed anonymous surveys before and after the imaging activity. RESULTS: Students were proficient at identifying the correct pre-specified skin lesions (86/88, 98%), capturing sufficient quality overview clinical images of the back and legs (41/42, 98%), and taking dermatoscopic images of the entire skin lesion (174/176, 99%). Regarding dermatoscopic image quality, 116 of 175 (66%) images were in focus. Out of focus images were attributed to poor skin contact. Groups that received feedback (n=4) were able to obtain a significantly higher proportion of in focus dermatoscopic images using their second camera compared to their first camera (16% to 72%, P<0.001). CONCLUSIONS: We identified several barriers that exist for participant-acquired dermatoscopic imaging. Instructions emphasizing the importance of skin contact are useful. Our results may help guide future patient-acquired teledermatoscopy efforts.

Incidence of liver injury among cancer patients receiving chemotherapy in an integrated health system.

PURPOSE: Using liver laboratory tests (LLTs), Hy's law is a method used to identify drug-induced liver injury (DILI), after excluding other causes. Elevated LLTs in chemotherapy-exposed patients may result from tumor effects or comorbidities. This study evaluated incidence of Hy's law in chemotherapy-treated cancer patients. METHODS: We identified breast, colorectal, and lung cancer patients diagnosed in 1 January 2000 to 31 December 2007 at a Midwestern health system. Using automated data, potential Hy's law (PHL) cases were defined by patterns of elevated LLTs suggestive of DILI. Among those treated with chemotherapy, we excluded PHL patients with pre-existing conditions that could cause liver injury, producing a cohort meeting Hy's law criteria, according to automated data. Medical record review, conducted among these automated data-derived Hy's law patients, further excluded those with causes of liver injury other than chemotherapy. RESULTS: Using automated data, among chemotherapy-exposed patients (N = 2788), 91 (3.3%) met PHL criteria using LLTs and 64 (2.3%) met Hy's law after excluding underlying liver injury using the International Classification of Diseases, 9th Revision codes. After a medical record review, 62 of 64 patients qualifying as Hy's law through automated data had other potential causes, leaving two patients (0.07%; 95%CI: 0.01-0.24%) with chemotherapy as a likely alternative cause of liver injury. CONCLUSIONS: Abnormal LLTs are common in chemotherapy-treated patients. Medical record review showed that the incidence of Hy's law events is rare. These data provide context for evaluating DILI in clinical trials and postmarketing surveillance of anticancer therapies, understanding that automated data alone may substantially overestimate the number of Hy's law cases.

Feasibility and Efficacy of Patient-Initiated Mobile Teledermoscopy for Short-term Monitoring of Clinically Atypical Nevi.

IMPORTANCE: Patient-driven mobile teledermoscopy may be applicable for monitoring of skin lesions. OBJECTIVE: To assess the feasibility, efficacy, and patient receptivity of teledermoscopy for short-term monitoring of clinically atypical nevi. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective cohort study performed at an institutional referral center in New York. Consecutive patients 18 years or older, with 1 or more clinically atypical nevi that required short-term monitoring and were accessible by a mobile imaging device were recruited for the study. All 34 patients consented to the study, and 29 completed follow-up. Dermoscopic images were obtained in the office-based setting by a dermatologist and with an iPhone by the patient at baseline and follow-up (3-4 months). Patients completed surveys that included questions about skincare awareness and attitudes toward teledermoscopy. Standard dermoscopic images were evaluated by the office-based dermatologist, and mobile dermoscopic images were sent via the Internet to a teledermatologist to evaluate image quality and presence of significant clinical lesion change. The decisions of the teledermatologist and office-based dermatologist were compared. MAIN OUTCOMES AND MEASURES: (1) Feasibility of using mobile dermatoscope by patients, (2) diagnostic concordance of teledermoscopy vs conventional office-based visit, and (3) patient receptivity to teledermoscopy for short-term monitoring of nevi. RESULTS: Of the 29 patients who completed the study, 28 (97%) were able to acquire baseline and follow-up images that were subsequently deemed evaluable by the teledermatologist. The diagnostic concordance between conventional office-based visits and teledermoscopy encounters was 0.87 (SE, 0.13) (κ statistic). In addition, patients reported high receptivity to teledermoscopy for short-term monitoring of nevi. CONCLUSIONS AND RELEVANCE: Results from this pilot study suggest that teledermoscopy is feasible and effective as a method for short-term monitoring of clinically atypical nevi. The implementation of teledermoscopy can potentially enhance patient convenience, optimize physician scheduling, and promote efficiency.

Patient characteristics and participation in a genetic study: a type 2 diabetes cohort.

BACKGROUND: Recruitment of large, diverse populations into genetic studies remains challenging. Potential strategies to overcome limitations include leveraging electronic health data and minimizing patient burden. We sought to describe the overall participation rate and identify characteristics associated with participation in a genetic substudy of patients with type 2 diabetes mellitus, in which patients were identified via electronic hospital data and asked to participate by providing DNA samples by mail. METHODS: During a phone interview, participants (n = 455) were asked to take part in a genetic substudy. Subjects verbally consenting were mailed saliva collection kits and written consent forms. We examined demographic and clinical variables associated with verbal consent and DNA kit return using logistic regression. RESULTS: Overall, 90% (n = 410) verbally consented to the genetic substudy during interviews. However, of those consenting, only 70% returned the DNA kit (n = 287). Among those consenting, after covariate adjustment, male sex (odds ratio [OR], 1.70; 95% confidence interval [CI], 1.09-2.65), African American race (OR, 0.61; 95% CI, 0.39-0.95), hemoglobin A1c (HbA1c) (OR, 0.87; 95% CI, 0.75-1.00), and physical activity (OR, 0.58; 95% CI, 0.37-0.91) were significantly associated with DNA kit return. CONCLUSIONS: To our knowledge, we are the first to demonstrate an inverse association between HbA1c and participation in genetic research, potentially indicating a compliance-related trait needing further exploration. The DNA kit return rate being notably lower than the verbal consent rate suggests that the greater convenience of a telephone/mail-in process did not drastically enhance full participation. Direct comparison to in-person donation may be warranted.

Patient perceptions of nonmelanoma skin cancer before diagnosis.

BACKGROUND: There is a paucity of data regarding patient perceptions of nonmelanoma skin cancer (NMSC). OBJECTIVE: To describe patients' perceptions of skin lesions before a diagnosis of NMSC. METHODS: This was a descriptive study in a private practice setting. Patients with a previous biopsy of NMSC who presented for treatment were eligible. A self-administered questionnaire assessed what patient perceptions of lesions diagnosed as NMSCs had been before they were aware of the diagnosis. Medical records were reviewed for tumor type, size, and location. RESULTS: One hundred sixty-three consecutive patients undergoing treatment for NMSC completed the questionnaire. The most common initial impressions of the lesion were skin cancer (20%), acne (19%), sore (10%), unknown (9%), dry skin (7%), age spot (6%), and injury (6%). Seventy-two percent of patients were the first to notice the lesion. Patients with a history of skin cancer were more likely to think the lesion was a skin cancer on initial impression (28% vs. 8%) (p < .001). CONCLUSIONS: Understanding how patients perceive their skin cancers may aid in targeting educational strategies and increase awareness of skin cancer risk. Our data suggest that there are important subtleties in self-identification that may need to be taken into consideration in any educational campaign targeting NMSC.