Direct-to-Consumer Broadcast Advertisements for Pharmaceuticals: Off-Label Promotion and Adherence to FDA Guidelines.

BACKGROUND: Direct-to-consumer (DTC) advertisements for prescription drugs in the United States are regulated by the Food and Drug Administration (FDA). Off-label promotion, or the advertisement of a drug for an indication not approved by the FDA, is prohibited. Our objective was to examine the presence of off-label promotion in broadcast DTC ads and to assess their adherence to FDA guidelines mandating fair balance in presentation of risks and benefits and prohibiting misleading advertisement claims. METHODS: All English-language broadcast DTC ads for prescription drugs that aired in the United States from January 2015 to July 2016 were obtained from AdPharm, an online collection of healthcare advertisements. Ad length was measured and adherence to FDA guidelines was assessed for several categories: key regulatory items, indicators of false or misleading ads, and indicators of fair balance in presentation of risks and benefits. RESULTS: Our sample included 97 unique DTC ads, representing 60 unique drugs and 67 unique drug-indication combinations. No ads described drug risks quantitatively, whereas drug efficacy was presented quantitatively in 25 (26%) ads. Thirteen (13%) ads, all for diabetes medications, suggested off-label uses for weight loss and blood pressure reduction. The most commonly advertised drugs were indicated for the treatment of inflammatory conditions (n = 12; 18%), diabetes or diabetic neuropathy (n = 11; 16%), bowel or bladder dysfunction (n = 6; 9%), and infections or allergic reaction (n = 6; 9%). More than three-quarters (n = 51; 76%) advertised drugs to treat chronic conditions. CONCLUSIONS: Few broadcast DTC ads were fully compliant with FDA guidelines. The overall quality of information provided in ads was low, and suggestions of off-label promotion were common for diabetes medications. The impact of current DTC ads and off-label marketing on patient and prescriber decisions merits further scrutiny.

Financial Incentives and Health Coaching to Improve Physical Activity Following Total Knee Replacement: A Randomized Controlled Trial.

OBJECTIVE: Most persons who undergo total knee replacement (TKR) do not increase their physical activity following surgery. We assessed whether financial incentives and health coaching would improve physical activity in persons undergoing TKR. METHODS: We designed a factorial randomized controlled trial among persons undergoing TKR for osteoarthritis. Subjects underwent normal perioperative procedures, including postoperative physical therapy, and were assigned to 1 of 4 arms: attention control, telephonic health coaching (THC), financial incentives (FI), or THC + FI. We objectively measured step counts and minutes of physical activity using a commercial accelerometer (Fitbit Zip) and compared the changes from pre-TKR to 6 months post-TKR across the 4 study arms. RESULTS: Of the 202 randomized subjects, 150 (74%) provided both pre-TKR and 6 months post-TKR accelerometer data. Among completers, the mean ± SE daily step count at 6 months ranged from 5,619 ± 381 in the THC arm to 7,152 ± 407 in the THC + FI arm (adjusting for baseline values). Daily step count 6 months post-TKR increased by 680 (95% confidence interval [95% CI] -94, 1,454) in the control arm, 274 (95% CI -473, 1,021) in the THC arm, 826 (95% CI 89, 1,563) in the FI arm, and 1,808 (95% CI 1,010, 2,606) in the THC + FI arm. Weekly physical activity increased by mean ± SE 14 ± 10, 14 ± 10, 16 ± 10, and 39 ± 11 minutes in the control, THC, FI, and THC + FI arms, respectively. CONCLUSION: A dual THC + FI intervention led to substantial improvements in step count and physical activity following TKR.

Implementation of a workplace intervention using financial rewards to promote adherence to physical activity guidelines: a feasibility study.

BACKGROUND: We designed and implemented the Brigham and Women's Wellness Initiative (B-Well), a single-arm study to examine the feasibility of a workplace program that used individual and team-based financial incentives to increase physical activity among sedentary hospital employees. METHODS: We enrolled sedentary, non-clinician employees of a tertiary medical center who self-reported low physical activity. Eligible participants formed or joined teams of three members and wore Fitbit Flex activity monitors for two pre-intervention weeks followed by 24 weeks during which they could earn monetary rewards. Participants were rewarded for increasing their moderate-to-vigorous physical activity (MVPA) by 10% from the previous week or for meeting the Centers for Disease Control and Prevention (CDC) physical activity guidelines (150 min of MVPA per week). Our primary outcome was the proportion of participants meeting weekly MVPA goals and CDC physical activity guidelines. Secondary outcomes included Fitbit-wear adherence and factors associated with meeting CDC guidelines more consistently. RESULTS: B-Well included 292 hospital employees. Participants had a mean age of 38 years (SD 11), 83% were female, 38% were obese, and 62% were non-Hispanic White. Sixty-three percent of participants wore the Fitbit ≥4 days per week for ≥20 weeks. Two-thirds were satisfied with the B-Well program, with 79% indicating that they would participate again. Eighty-six percent met either their personal weekly goal or CDC physical activity guidelines for at least 6 out of 24 weeks, and 52% met their goals or CDC physical activity guidelines for at least 12 weeks. African Americans, non-obese subjects, and those with lower impulsivity scores reached CDC guidelines more consistently. CONCLUSIONS: Our data suggest that a financial incentives-based workplace wellness program can increase MVPA among sedentary employees. These results should be reproduced in a randomized controlled trial. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02850094 . Registered July 27, 2016 [retrospectively registered].

Association between activity limitations and pain in patients scheduled for total knee arthroplasty.

BACKGROUND: Historically, persons scheduled for total knee arthroplasty (TKA) have reported severe pain with low demand activities such as walking, but recent data suggests that TKA recipients may have less preoperative pain. Little is known about people who elect TKA with low levels of preoperative pain. To better understand current TKA utilization, we evaluated the association between preoperative pain and difficulty performing high demand activities, such as kneeling and squatting, among TKA recipients. METHODS: We used baseline data from a randomized control trial designed to improve physical activity following TKA. Prior to TKA, participants were categorized according to Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain scores: Low (0-25), Medium (26-40), and High (41-100). Within each group, limitations in both low demand and high demand activities were assessed. RESULTS: The sample consisted of 202 persons with a mean age of 65 (SD 8) years; 21 %, 34 %, and 45 % were categorized in the Low, Medium, and High Pain groups, respectively. Of the Low Pain group, 60 % reported at least one of the following functional limitations: limited flexion, limp, limited walking distance, and limitations in work or housework. While only 12 % of the Low Pain group reported at least moderate pain with walking on a flat surface, nearly all endorsed at least moderate difficulty with squatting and kneeling. CONCLUSIONS: A substantial number of persons scheduled for TKA report Low WOMAC Pain (≤25) prior to surgery. Persons with Low WOMAC Pain scheduled for TKA frequently report substantial difficulty with high demand activities such as kneeling and squatting. Studies of TKA appropriateness and effectiveness for patients with low WOMAC Pain should include measures of these activities. TRIAL REGISTRATION: Identifier NCT01970631 ; Registered 23 October 2013.

Reliability and Accuracy of Cross-sectional Radiographic Assessment of Severe Knee Osteoarthritis: Role of Training and Experience.

OBJECTIVE: To dêtermine the reliability of radiographic assessment of knee osteoarthritis (OA) by nonclinician readers compared to an experienced radiologist. METHODS: The radiologist trained 3 nonclinicians to evaluate radiographic characteristics of knee OA. The radiologist and nonclinicians read preoperative films of 36 patients prior to total knee replacement. Intrareader and interreader reliability were measured using the weighted κ statistic and intraclass correlation coefficient (ICC). Scores κ < 0.20 indicated slight agreement, 0.21-0.40 fair, 0.41-0.60 moderate, 0.61-0.80 substantial, and 0.81-1.0 almost perfect agreement. RESULTS: Intrareader reliability among nonclinicians (κ) ranged from 0.40 to 1.0 for individual radiographic features and 0.72 to 1.0 for Kellgren-Lawrence (KL) grade. ICC ranged from 0.89 to 0.98 for the Osteoarthritis Research Society International (OARSI) summary score. Interreader agreement among nonclinicians ranged from κ of 0.45 to 0.94 for individual features, and 0.66 to 0.97 for KL grade. ICC ranged from 0.87 to 0.96 for the OARSI Summary Score. Interreader reliability between nonclinicians and the radiologist ranged from κ of 0.56 to 0.85 for KL grade. ICC ranged from 0.79 to 0.88 for the OARSI Summary Score. CONCLUSION: Intrareader and interreader agreement was variable for individual radiograph features but substantial for summary KL grade and OARSI Summary Score. Investigators face tradeoffs between cost and reader experience. These data suggest that in settings where costs are constrained, trained nonclinicians may be suitable readers of radiographic knee OA, particularly if a summary score (KL grade or OARSI Score) is used to determine radiographic severity.

Effectiveness of Knee Injury and Anterior Cruciate Ligament Tear Prevention Programs: A Meta-Analysis.

OBJECTIVE: Individuals frequently involved in jumping, pivoting or cutting are at increased risk of knee injury, including anterior cruciate ligament (ACL) tears. We sought to use meta-analytic techniques to establish whether neuromuscular and proprioceptive training is efficacious in preventing knee and ACL injury and to identify factors related to greater efficacy of such programs. METHODS: We performed a systematic literature search of studies published in English between 1996 and 2014. Intervention efficacy was ascertained from incidence rate ratios (IRRs) weighted by their precision (1/variance) using a random effects model. Separate analyses were performed for knee and ACL injury. We examined whether year of publication, study quality, or specific components of the intervention were associated with efficacy of the intervention in a meta-regression analysis. RESULTS: Twenty-four studies met the inclusion criteria and were used in the meta-analysis. The mean study sample was 1,093 subjects. Twenty studies reported data on knee injury in general terms and 16 on ACL injury. Maximum Jadad score was 3 (on a 0-5 scale). The summary incidence rate ratio was estimated at 0.731 (95% CI: 0.614, 0.871) for knee injury and 0.493 (95% CI: 0.285, 0.854) for ACL injury, indicating a protective effect of intervention. Meta-regression analysis did not identify specific intervention components associated with greater efficacy but established that later year of publication was associated with more conservative estimates of intervention efficacy. CONCLUSION: The current meta-analysis provides evidence that neuromuscular and proprioceptive training reduces knee injury in general and ACL injury in particular. Later publication date was associated with higher quality studies and more conservative efficacy estimates. As study quality was generally low, these data suggest that higher quality studies should be implemented to confirm the preventive efficacy of such programs.

Is there an association between whole-body pain with osteoarthritis-related knee pain, pain catastrophizing, and mental health?

BACKGROUND: Greater levels of self-reported pain, pain catastrophizing, and depression have been shown to be associated with persistent pain and functional limitation after surgeries such as TKA. It would be useful for clinicians to be able to measure these factors efficiently. QUESTIONS/PURPOSES: We asked: (1) What is the association of whole-body pain with osteoarthritis (OA)-related knee pain, function, pain catastrophizing, and mental health? (2) What is the sensitivity and specificity for different cutoffs for body pain diagram region categories in relation to pain catastrophizing? METHODS: Patients (n = 267) with knee OA undergoing elective TKA at one academic center and two community orthopaedic centers were enrolled before surgery in a prospective cohort study. Questionnaires included the WOMAC Pain and Function Scales, Pain Catastrophizing Scale (PCS), Mental Health Inventory-5 (MHI-5), and a pain body diagram. The diagram documents pain in 19 anatomic areas. Based on the distribution of the anatomic areas, we established six different body regions. Our analyses excluded the index (surgically treated) knee. Linear regression was used to evaluate the association between the total number of nonindex painful sites on the whole-body pain diagram and measures of OA-related pain and function, mental health, and pain catastrophizing. Generalized linear regression was used to evaluate the association between the number of painful nonindex body regions (categorized as 0; 1-2; or 3-6) with our measures of interest. All models were adjusted for age, sex, and number of comorbid conditions. The cohort included 63% females and the mean age was 66 years (SD, 9 years). With removal of the index knee, the median pain diagram score was 2 (25(th), 75(th) percentiles, 1, 4) with a range of 0 to 15. The median number of painful body regions was 2 (25(th), 75(th) percentiles, 1, 3). RESULTS: After adjusting for age, sex, and number of comorbid conditions, we found modest associations between painful body region categories and mean scores for WOMAC physical function (r = 0.22, p < 0.001), WOMAC pain (r = 0.20, p = 0.001), MHI-5 (r = -0.31, p < 0.001), and PCS (r = 0.27, p < 0.001). A nonindex body pain region score greater than 0 had 100% (95% CI, 75%-100%) sensitivity for a pain catastrophizing score greater than 30 but a specificity of just 23% (95% CI, 18%-29%) . A score of 3 or greater had greater specificity (73%; 95% CI, 66%-79%) but lower sensitivity (53%; 95% CI, 27%-78%). CONCLUSIONS: We found modest associations between the number of painful sites on a whole-body pain diagram and the number of painful body regions and measures of OA-related pain, function, pain catastrophizing, and mental health. Patients with higher self-reported body pain region scores might benefit from further evaluation for depression and pain catastrophizing. LEVEL OF EVIDENCE: Level III, therapeutic study.

Development and feasibility of a personalized, interactive risk calculator for knee osteoarthritis.

BACKGROUND: The incidence of knee osteoarthritis (OA) is rising. While several risk factors have been associated with the development of knee OA, this information is not readily accessible to those at risk for osteoarthritis. Risk calculators have been developed for several prevalent chronic conditions but not for OA. Using published evidence on established risk factors, we developed an interactive, personalized knee OA risk calculator (OA Risk C) and conducted a pilot study to evaluate its acceptability and feasibility. METHODS: We used the Osteoarthritis Policy (OAPol) Model, a validated, state-transition simulation of the natural history and management of OA, to generate data for OA Risk C. Risk estimates for calculator users were based on a set of demographic and clinical factors (age, sex, race/ethnicity, obesity) and select risk factors (family history of knee OA, occupational exposure, and history of knee injury). OA Risk C presents personalized risk of knee OA in several ways to maximize understanding among a wide range of users. We conducted a study of 45 subjects in a primary care setting to establish the feasibility and acceptability of the OA risk calculator. Pilot study participants were asked several questions regarding ease of use, clarity of presentation, and clarity of the graphical representation of their risk. These questions used a five-level agreement scale ranging from strongly disagree to strongly agree. RESULTS: OA Risk C depicts information about users' risk of symptomatic knee OA in 5 year intervals. Study participants estimated their lifetime risk at 38 %, while their actual lifetime risk, as estimated by OA Risk C, was 25 %. Eighty-four percent of pilot study participants reported that OA Risk C was easy to understand, and 89 % agreed that the graphs depicting their risk were clear and comprehensible. CONCLUSIONS: We have developed a personalized, computer-based OA risk calculator that is easy to use. OA Risk C may be utilized to estimate individuals' knee OA risk and to deliver educational and behavioral interventions focused on osteoarthritis risk reduction.

Lifetime medical costs of knee osteoarthritis management in the United States: impact of extending indications for total knee arthroplasty.

OBJECTIVE: The impact of increasing utilization of total knee arthroplasty (TKA) on lifetime costs in persons with knee osteoarthritis (OA) is understudied. METHODS: We used the Osteoarthritis Policy Model to estimate total lifetime costs and TKA utilization under a range of TKA eligibility criteria among US persons with symptomatic knee OA. Current TKA utilization was estimated from the Multicenter Osteoarthritis Study and calibrated to Health Care Cost and Utilization Project data. OA treatment efficacy and toxicity were drawn from published literature. Costs in 2013 dollars were derived from Medicare reimbursement schedules and Red Book Online. Time costs were derived from published literature and the US Bureau of Labor Statistics. RESULTS: Estimated average discounted (3% per year) lifetime costs for persons diagnosed with knee OA were $140,300. Direct medical costs were $129,600, with $12,400 (10%) attributable to knee OA over 28 years. OA patients spent a mean ± SD of 13 ± 10 years waiting for TKA after failing nonsurgical regimens. Under current TKA eligibility criteria, 54% of knee OA patients underwent TKA over their lifetimes. Estimated OA-related discounted lifetime direct medical costs ranged from $12,400 (54% TKA uptake) when TKA eligibility was limited to Kellgren/Lawrence grades 3 or 4 to $16,000 (70% TKA uptake) when eligibility was expanded to include symptomatic OA with a lesser degree of structural damage. CONCLUSION: Because of low efficacy of nonsurgical regimens, knee OA treatment-attributable costs are low, representing a small portion of all costs for OA patients. Expanding TKA eligibility increases OA-related costs substantially for the population, underscoring the need for more effective nonoperative therapies.