SEAMARK: phase II study of first-line encorafenib and cetuximab plus pembrolizumab for MSI-H/dMMR BRAFV600E-mutant mCRC.

Patients with both BRAF V600E mutations and microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC) have poor prognosis. Currently, there are no specifically targeted first-line treatment options indicated for patients with mCRC whose tumors harbor both molecular aberrations. Pembrolizumab is a checkpoint inhibitor approved for the treatment of MSI-H/dMMR mCRC, and the BRAF inhibitor encorafenib, in combination with cetuximab, is approved for previously treated BRAF V600E-mutant mCRC. Combination of pembrolizumab with encorafenib and cetuximab may synergistically enhance antitumor activity in patients with BRAF V600E-mutant, MSI-H/dMMR mCRC. SEAMARK is a randomized phase II study comparing the efficacy of the combination of pembrolizumab with encorafenib and cetuximab versus pembrolizumab alone in patients with previously untreated BRAF V600E-mutant, MSI-H/dMMR mCRC.

Colorectal cancer (CRC) occurs when there is an abnormal growth of cells (known as a tumor) in the colon or rectum. Some people with CRC have changes in their tumor genes (known as gene mutations). A gene is a piece of DNA that tells the cell to make specific molecules, such as proteins. Mutations in a gene called BRAF can turn on signals that help the cancer cells grow. Gene mutations that impair DNA repair mechanisms can also make the cancer cells grow more quickly and allow the immune system to detect the cancer cells as being foreign to the body. Targeted therapy is a type of cancer treatment that turns off specific genes and proteins involved in cancer cell survival and growth. BRAF and EGFR inhibitors are targeted therapies that work well together in treating people with BRAF-mutant CRC. BRAF proteins can help cancer cells grow, and BRAF inhibitors block these proteins to prevent, slow, or stop the growth of the cancer cells. Immunotherapy is a type of cancer treatment that helps a person's immune system fight cancer. Immunotherapy is effective for treating CRC that has mutations in the DNA repair mechanisms. By combining targeted therapy and immunotherapy, patients may be able to live longer without their disease getting worse. In the SEAMARK study, we will use a treatment combination including a BRAF inhibitor (encorafenib), an EGFR inhibitor (cetuximab) and an immunotherapy (pembrolizumab) in patients with CRC who have a BRAF mutation and deficiencies in the DNA repair mechanism. Clinical Trial Registration: NCT05217446 (ClinicalTrials.gov), 2021-003715-26 (EudraCT).

Sunitinib in patients with pancreatic neuroendocrine tumors: update of safety data.

AIM: To describe the long-term safety of sunitinib in patients with progressive, well-differentiated, advanced/metastatic pancreatic neuroendocrine tumors. PATIENTS & METHODS: Sunitinib- and placebo-treated patients from the Phase III study continued to receive sunitinib (37.5 mg on a continuous daily-dosing regimen) in two open-label extension studies. RESULTS: Median (range) treatment exposure: 30.2 (0.7-269.4) and 87.1 (3.9-319.4) weeks for medium-term (n = 41) and long-term-treated (n = 61) populations, respectively. All patients experienced ≥1 adverse event (AE); 47 (45.6%) reported serious AEs. Common all-causality AEs: diarrhea (63.1%); neutropenia (43.7%); abdominal pain (40.8%). Fifteen (14.6%) patients discontinued treatment due to treatment-related AEs. CONCLUSION: The safety of extended sunitinib treatment was consistent with the known safety profile of sunitinib in pancreatic neuroendocrine tumors.

Pharmacogenomic analyses of sunitinib in patients with pancreatic neuroendocrine tumors.

Aim: Evaluate associations between clinical outcomes and SNPs in patients with well-differentiated pancreatic neuroendocrine tumors receiving sunitinib. Patients & methods: Kaplan-Meier and Cox proportional hazards models were used to analyze the association between SNPs and survival outcomes using data from a sunitinib Phase IV (genotyped, n = 56) study. Fisher's exact test was used to analyze objective response rate and genotype associations. Results: After multiplicity adjustment, progression-free and overall survivals were not significantly correlated with SNPs; however, a higher objective response rate was significantly associated with IL1B rs16944 G/A versus G/G (46.4 vs 4.5%; p = 0.001). Conclusion: IL1B SNPs may predict treatment response in patients with pancreatic neuroendocrine tumors. VEGF pathway SNPs are potentially associated with survival outcomes.

Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: a non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial.

BACKGROUND: Previous studies combining PD-1 checkpoint inhibitors with tyrosine kinase inhibitors of the VEGF pathway have been characterised by excess toxicity, precluding further development. We hypothesised that axitinib, a more selective VEGF inhibitor than others previously tested, could be combined safely with pembrolizumab (anti-PD-1) and yield antitumour activity in patients with treatment-naive advanced renal cell carcinoma. METHODS: In this ongoing, open-label, phase 1b study, which was done at ten centres in the USA, we enrolled patients aged 18 years or older who had advanced renal cell carcinoma (predominantly clear cell subtype) with their primary tumour resected, and at least one measureable lesion, Eastern Cooperative Oncology Group performance status 0-1, controlled hypertension, and no previous systemic therapy for renal cell carcinoma. Eligible patients received axitinib plus pembrolizumab in a dose-finding phase to estimate the maximum tolerated dose, and additional patients were enrolled into a dose-expansion phase to further establish safety and determine preliminary efficacy. Axitinib 5 mg was administered orally twice per day with pembrolizumab 2 mg/kg given intravenously every 3 weeks. We assessed safety in all patients who received at least one dose of axitinib or pembrolizumab; antitumour activity was assessed in all patients who received study treatment and had an adequate baseline tumour assessment. The primary endpoint was investigator-assessed dose-limiting toxicity during the first two cycles (6 weeks) to estimate the maximum tolerated dose and recommended phase 2 dose. This study is registered with ClinicalTrials.gov, number NCT02133742. FINDINGS: Between Sept 23, 2014, and March 25, 2015, we enrolled 11 patients with previously untreated advanced renal cell carcinoma to the dose-finding phase and between June 3, 2015, and Oct 13, 2015, we enrolled 41 patients to the dose-expansion phase. All 52 patients were analysed together. No unexpected toxicities were observed. Three dose-limiting toxicities were reported in the 11 patients treated during the 6-week observation period (dose-finding phase): one patient had a transient ischaemic attack and two patients were only able to complete less than 75% of the planned axitinib dose because of treatment-related toxicity. At the data cutoff date (March 31, 2017), 25 (48%) patients were still receiving study treatment. Grade 3 or worse treatment-related adverse events occurred in 34 (65%) patients; the most common included hypertension (n=12 [23%]), diarrhoea (n=5 [10%]), fatigue (n=5 [10%]), and increased alanine aminotransferase concentration (n=4 [8%]). The most common potentially immune-related adverse events (probably related to pembrolizumab) included diarrhoea (n=15 [29%]), increased alanine aminotransferase concentration (n=9 [17%]) or aspartate aminotransferase concentration (n=7 [13%]), hypothyroidism (n=7 [13%]), and fatigue (n=6 [12%]). 28 (54%) patients had treatment-related serious adverse events. At data cutoff, 38 (73%; 95% CI 59·0-84·4) patients achieved an objective response (complete or partial response). INTERPRETATION: The treatment combination of axitinib plus pembrolizumab is tolerable and shows promising antitumour activity in patients with treatment-naive advanced renal cell carcinoma. Whether or not the combination works better than a sequence of VEGF pathway inhibition followed by an anti-PD-1 therapy awaits the completion of a phase 3 trial comparing axitinib plus pembrolizumab with sunitinib monotherapy (NCT02853331). FUNDING: Pfizer Inc.

Efficacy and Safety of Sunitinib in Patients with Well-Differentiated Pancreatic Neuroendocrine Tumours.

BACKGROUND: In a phase III study, sunitinib led to a significant increase in progression-free survival (PFS) versus placebo in patients with pancreatic neuroendocrine tumours (panNETs). This study was a post-marketing commitment to support the phase III data. METHODS: In this ongoing, open-label, phase IV trial (NCT01525550), patients with progressive, advanced unresectable/metastatic, well-differentiated panNETs received continuous sunitinib 37.5 mg once daily. Eligibility criteria were similar to those of the phase III study. The primary endpoint was investigator-assessed PFS per Response Evaluation Criteria in Solid Tumours v1.0 (RECIST). Other endpoints included PFS per Choi criteria, overall survival (OS), objective response rate (ORR), and adverse events (AEs). RESULTS: Sixty-one treatment-naive and 45 previously treated patients received sunitinib. By March 19, 2016, 82 (77%) patients had discontinued treatment, mainly due to disease progression. Median treatment duration was 11.7 months. Investigator-assessed median PFS per RECIST (95% confidence interval [CI]) was 13.2 months (10.9-16.7): 13.2 (7.4-16.8) and 13.0 (9.2-20.4) in treatment-naive and previously treated patients, respectively. ORR (95% CI) per RECIST was 24.5% (16.7-33.8) in the total population: 21.3% (11.9-33.7) in treatment-naive and 28.9% (16.4-44.3) in previously treated patients. Median OS, although not yet mature, was 37.8 months (95% CI, 33.0-not estimable). The most common treatment-related AEs were neutropenia (53.8%), diarrhoea (46.2%), and leukopenia (43.4%). CONCLUSIONS: This phase IV trial confirms sunitinib as an efficacious and safe treatment option in patients with advanced/metastatic, well-differentiated, unresectable panNETs, and supports the phase III study outcomes. AEs were consistent with the known safety profile of sunitinib.

Updated Efficacy and Safety Outcomes for Patients with Well-Differentiated Pancreatic Neuroendocrine Tumors Treated with Sunitinib.

BACKGROUND: Sunitinib prolonged progression-free survival (PFS) versus placebo in patients with metastatic pancreatic neuroendocrine tumors (panNETs) in a phase III trial. The efficacy and safety of sunitinib in patients with panNETs were confirmed in an open-label phase IV trial. OBJECTIVE: To assess the clinical benefit with sunitinib using the combined data from these trials. PATIENTS AND METHODS: An updated overall survival (OS) in patients with panNETs for the phase IV trial was provided, and an analysis of results from the sunitinib-treated combined cohort from the phase III and IV trials (combined cohort) was conducted to assess PFS, OS, and objective response rate (ORR). RESULTS: The updated median OS for the phase IV trial was 54.1 months (95% CI 37.9-not reached). Investigator-assessed median PFS for the combined cohort (n = 102) was 12.9 months (95% CI 7.4-16.7) with a significant benefit versus placebo in the phase III trial (n = 35) (HR 0.429; 95% CI 0.245-0.752; p = 0.001). Median OS could not be calculated for the combined cohort or placebo group due to the high number of patients censored; however, the estimated HR of 0.303 (CI 0.100-0.921; p = 0.013) favored sunitinib. ORR for the combined cohort was 16.7% (95% CI 10.0-25.3). Sunitinib was well tolerated in both trials with a safety profile similar to previously seen in other studies. CONCLUSIONS: The combined analysis of these studies confirms the objective tumor responses and improvements in PFS observed in the initial phase III trial, providing further support for the clinical benefit of sunitinib in patients with advanced panNETs. CLINICALTRIALS. GOV IDENTIFIERS: NCT00428597 and NCT01525550.

Axitinib plus pembrolizumab in patients with advanced renal-cell carcinoma: Long-term efficacy and safety from a phase Ib trial.

BACKGROUND: Axitinib plus pembrolizumab showed superior overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) versus sunitinib in a randomised phase III trial in patients with advanced renal-cell carcinoma (RCC). We report long-term efficacy and safety of the axitinib/pembrolizumab from the phase I trial (NCT02133742), after 46-55 months from study initiation (data cut-off date, 23rd July 2019). METHODS: Fifty-two treatment-naïve patients with advanced RCC were treated with oral axitinib 5 mg twice daily and intravenous pembrolizumab 2 mg/kg every 3 weeks. PFS, duration of response (DoR) and OS were summarised using the Kaplan-Meier method. RESULTS: At a median follow-up of 42.7 months (95% confidence interval [CI]: 41.1-44.1), median OS was not reached; 38 (73.1%) patients were alive. The probability of being alive at 4 years was 66.8% (95% CI: 49.1-79.5). Median PFS in the overall population was 23.5 months (95% CI: 15.4-30.4). ORR was 73.1%; five patients had complete response. Median DoR was 22.1 months (95% CI: 15.1-34.5). Grade III/IV adverse events (AEs) were reported in 38 (73.1%) patients and 20 (38.5%) discontinued treatment because of AEs: 17 (32.7%) discontinued axitinib, 13 (25.0%) discontinued pembrolizumab, and 10 (19.2%) discontinued both drugs. Common AEs included diarrhoea (84.6%), fatigue (80.8%), hypertension (53.8%), cough (48.1%) and dysphonia (48.1%). There were no new AE terms reported and no treatment-related deaths. CONCLUSIONS: In patients with advanced RCC with ~4 years of follow-up, combination axitinib/pembrolizumab continued to demonstrate clinical benefit, with no new safety signals.

Measuring attractiveness for abuse of prescription opioids.

OBJECTIVE: Prescription opioids are the second most misused/abused drug in the United States behind only marijuana. Recreational prescription opioid users appear to prefer some products over others; however, the extent to which attributes of any particular formulation account for such preferences has yet to be determined. The Opioid Attractiveness Technology Scaling was developed to identify the particular features of a prescription opioid that are relevant to its attractiveness for recreational use, and to use these features to model attractiveness for recreational use of particular prescription opioid formulations. DESIGN: Four hundred and ninety-one self-reported recreational prescription opioid users identified 43 product features as being relevant to determining whether a product is "attractive" or "unattractive" for recreational use. Average ratings were used to determine appropriate weights to be applied to the features. A factor analysis yielded 10, highly differentiated factors. Five hundred and sixty-four prescription opioid abusers were then asked to rate the extent to which the 43 features identified in Study 1 were relevant to specific prescription opioid products they had used. RESULTS: Respondents provided an overall preference rating of these products and a model was created. A random intercept model yielded a significant pseudo R(2) of 0.14 (chi-square = 310.02, degrees of freedom [df] = 10, P < 0.001). The model fit least well, albeit significantly, for abusers who preferred to swallow the drug (pseudo R(2) = 0.06; chi-square = 55.52, df = 10, P < 0.001) and best for those who preferred to inject (pseudo R(2) = 0.37; chi-square = 199.34, df = 10, P < 0.001). CONCLUSIONS: The relevance of the model is discussed along with possible modifications that might allow prediction of "attractiveness" of "abuse deterrent" formulations that have not yet been marketed.

Angiogenic and Immune-Related Biomarkers and Outcomes Following Axitinib/Pembrolizumab Treatment in Patients with Advanced Renal Cell Carcinoma.

PURPOSE: Combined axitinib/pembrolizumab is approved for advanced renal cell carcinoma (aRCC). This exploratory analysis examined associations between angiogenic and immune-related biomarkers and outcomes following axitinib/pembrolizumab treatment. PATIENTS AND METHODS: Prospectively defined retrospective correlative exploratory analyses tested biospecimens from 52 treatment-naïve patients receiving axitinib and pembrolizumab (starting doses 5 mg twice daily and 2 mg/kg respectively, every 3 weeks). Tumor tissue, serum, and whole blood samples were collected at baseline, at cycle 2 day 1 (C2D1), and end of treatment (EOT) for blood-based samples. Clinical outcomes were objective response rate (ORR) and progression-free survival (PFS). RESULTS: Higher baseline tumor levels of CD8 showed a trend toward longer PFS (HR 0.4; P = 0.091). Higher baseline serum levels of CXCL10 (P = 0.0197) and CEACAM1 (P = 0.085) showed a trend toward better ORR and longer PFS, respectively. Patients for whom IL6 was not detected at baseline had longer PFS versus patients for whom it was detected (HR 0.4; P = 0.028). At C2D1 and/or EOT, mainly immune-related biomarkers showed any association with better outcomes. The genes CA9 (P = 0.084), HIF1A (P = 0.064), and IFNG (P = 0.073) showed trending associations with ORR, and AKT3 (P = 0.0145), DDX58 (P = 0.0726), GZMA (P = 0.0666), LCN2 (NGAL; P = 0.0267), and PTPN11 (P = 0.0287) with PFS. CONCLUSIONS: With combined axitinib/pembrolizumab treatment in patients with aRCC, mostly immune-related biomarkers are associated with better treatment outcomes. This exploratory analysis has identified some candidate biomarkers to consider in future prospective testing.

Validation of the revised Screener and Opioid Assessment for Patients with Pain (SOAPP-R).

UNLABELLED: The original Screener and Opioid Assessment for Patients with Pain (SOAPP) is a conceptually derived self-report questionnaire designed to predict aberrant medication-related behaviors among chronic pain patients considered for long-term opioid therapy. The purpose of this study was to develop and validate an empirically derived version of the SOAPP (SOAPP-R) that addresses some limitations of the original SOAPP. In successive steps, items were reduced from an initial pool of 142 to a 97-item beta version. The beta version was administered to 283 chronic pain patients receiving long-term opioid therapy. Items were evaluated based on data collected at follow-up, including correlation with the Aberrant Drug Behavior Index (ADBI), derived from interview data, physician ratings, and urine toxicology screens. Twenty-four items were retained and comprise the final SOAPP-R. Coefficient alpha was .88, and receiver operating characteristics curve analysis yielded an area under the curve of .81 (P < .001). A cutoff score of 18 showed adequate sensitivity (.81) and specificity (.68). The obtained psychometrics, along with the use of a predictive criterion that goes beyond self-report, suggest that the SOAPP-R is an improvement over the original version in screening risk potential for aberrant medication-related behavior among persons with chronic pain. PERSPECTIVE: There is a need for a screener for abuse risk in patients prescribed opioids for pain. This study presents a revised version of the SOAPP-R that is empirically derived with good reliability and validity but is less susceptible to overt deception than the original SOAPP version 1.

Update on prescription monitoring in clinical practice: a survey study of prescription monitoring program administrators.

OBJECTIVE: Prescription drug abuse and undertreatment of pain are public health priorities in the United States. Few options to manage these problems are balanced, in simultaneously supporting pain relief and deterring prescription drug abuse. Prescription monitoring programs (PMPs) potentially offer a balanced approach; however, the medical/scientific communities are not well informed about their current status and potential risks/benefits. The purpose of this study was to provide a benchmark of the current status of PMPs for healthcare providers upon which to engage PMP administrators. DESIGN: A Web survey of current PMP directors with a telephone follow-up conducted in June-July 2006 regarding goals, data captured, data sharing procedures, healthcare provider training, and evaluation efforts. RESULTS: Eighteen of 23 states with operating PMPs at that time participated. Eleven programs allowed physician access to PMP data. Data were delivered by mail (N = 6), fax (N = 8), e-mail (N = 1), and Websites (N = 8). Eight programs provided data to providers within 1 hour. Three states have developed provider PMP usage guidelines. Eight states developed or are developing educational programs. Two states completed or are conducting evaluations of the public health impact of PMP implementation. Five states have begun utilizing PMP data as an epidemiological tool. CONCLUSIONS: Initial public safety orientation of PMPs is evolving to include improving public health and patient care. Beginning with efforts to engage healthcare providers through data sharing and education, and progressively including program evaluation on public health and patient care, our results suggest a rapid movement in the direction of utilization of PMPs to improve health care.

Retrospective accounts of initial subjective effects of opioids in patients treated for pain who do or do not develop opioid addiction: a pilot case-control study.

This pilot case-control study retrospectively assessed between-groups differences in subjective opioid effects in patients treated for the first time with opioids for chronic pain. Cases were individuals in an inpatient substance abuse treatment center for primary prescription opioid addiction whose initial exposure to prescription opioids was reported for chronic pain. Controls had not developed prescription opioid addiction as measured in part by close monitoring on long-term opioid therapy at a pain management center. Twenty subjects in each group completed a battery of measures to capture data related to the individual's first exposure to prescription opioids. The Morphine Benzedrine Group subscale of an adapted 49-item Addiction Center Research Inventory (ARCI), designed to measure euphoria and other drug effects, showed an average score of 8.70 (+/-4.18) in cases versus 2.55 (+/-3.36) in controls (p<0.001), indicating a significantly greater "euphoric" effect of opioids in the cases compared to the controls. Differences in the subjective response to opioids suggest that: (1) a subgroup of patients does develop euphoria when taking opioids for pain, which may be a risk factor for eventual development of prescription opioid addiction; and (2) subjective effects predictive of eventual addiction may include stimulation and other experiences not typically associated with opioids.

Psychiatric history and psychologic adjustment as risk factors for aberrant drug-related behavior among patients with chronic pain.

OBJECTIVE: To investigate the role of psychiatric history and psychologic adjustment on aberrant drug-related behavior among patients prescribed opioids for noncancer pain. METHODS: Two hundred twenty-eight patients prescribed opioids for chronic pain were classified as either high or low on psychiatric morbidity on the basis of their responses on the psychiatric subscale of the Prescription Drug Use Questionnaire (PDUQ). They also completed the Brief Pain Inventory (BPI), Screener and Opioid Assessment for Pain Patients (SOAPP), and the Current Medication Misuse Measure (COMM). Patients were followed for 5 months and submitted a urine toxicology screen, and their treating physician completed the Prescription Opioid Therapy Questionnaire (POTQ). On the basis of the results from the SOAPP, COMM, POTQ, and urine screens, patients were classified as positive or negative on the Drug Misuse Index (DMI). RESULTS: One hundred and three (N=103) of the patients (45%) were classified in the low psychiatric group (Low Psych) whereas 55% (N=125) were classified in the high psychiatric morbidity group (High Psych). High Psych patients were significantly younger than Low Psych patients and had been taking opioids longer (P<0.05). The High Psych group showed significantly higher SOAPP and COMM scores than the Low Psych patients (P<0.001), had a greater frequency of abnormal urine toxicology screens (P<0.01), and significantly higher scores on the DMI (P<0.001). A consistent association was found between psychiatric morbidity and prescription opioid misuse in chronic pain patients. DISCUSSION: Psychiatric factors, such as a history of mood disorder, psychologic problems, and psychosocial stressors, may place patients at risk for misuse of prescription opioids. Future studies to elucidate the risk of medication misuse and aberrant drug behavior among this patient population are needed.

Development and validation of an Opioid Attractiveness Scale: a novel measure of the attractiveness of opioid products to potential abusers.

BACKGROUND: The growing trends in opioid abuse, assessment of the abuse liability of prescription opioid products, and growing efforts by the pharmaceutical industry to develop 'abuse-resistant' formulations highlight a need to understand the features that make one product more 'attractive' than another to potential abusers. We developed a scale to measure the 'attractiveness' of prescription opioids to potential abusers, and used the scale to measure the relative attractiveness of 14 opioid analgesic products. METHODS: First, the concept of attractiveness was empirically defined with a group of prescription opioid abusers and experts in opioid abuse using a process called Concept Mapping. Abuse liability consisted of two components: factors intrinsic to the drug formulation (e.g., speed of onset, duration) and factors extrinsic to drug formulation (e.g., availability, availability of alternatives, cost). A 17-item Opioid Attractiveness Scale (OAS) was constructed, focusing on factors intrinsic to the drug product. RESULTS: A total of 144 individuals participated in tests of validity and reliability. Internal consistency was excellent (Cronbach's alpha = 0.85-0.94). Drug rankings based on OAS scores achieved good inter-rater agreement (Kendall's W 0.37, p < 0.001). Agreement on drug OAS scores between the developmental sample and a confirmation sample was good (IntraClass Correlations [ICC] of 0.65-0.69). Global ratings of overall attractiveness of the 14 selected opioid products by substance abuse counselors corresponded with the rankings based on OAS ratings of the abuser group. Finally, substance abuse counselors completed the OAS, yielding a high level of correspondence with ratings by the abuser group (ICC = 0.83, p = 0.002). The OAS differentiated attractiveness among 14 selected pharmaceutical opioid products. OxyContin, Dilaudid, and Percocet were ranked highest (most attractive); Talwin NX and Duragesic were ranked lowest (least attractive). CONCLUSION: An initial examination of the psychometric properties of the OAS suggests that it is a valid and reliable scale. The OAS may be useful in providing important guidance on product features that are attractive to potential abusers.

Validation of a screener and opioid assessment measure for patients with chronic pain.

There has been a need for a brief assessment tool for providers who treat chronic pain patients to determine potential risk of abuse when prescribed opioids for pain. The purpose of this study was to develop and begin the validation of a self-administered screening tool (Screener and Opioid Assessment for Patients with Pain, SOAPP) for chronic pain patients considered for long-term opioid therapy. A consensus of 26 pain and addiction experts was obtained on important characteristics of chronic pain patients that predict future medication misuse using concept mapping. A 24-item SOAPP (version 1.0) was developed based on this consensus and was administered to 175 patients who were taking opioids for chronic pain. After 6 months, 95 of these patients were re-evaluated. Validation of the SOAPP was conducted by identifying those patients exhibiting aberrant drug-related behavior as determined by any of the following: a positive score on the Prescription Drug Use Questionnaire (PDUQ) interview, positive urine toxicology screen, and/or ratings by staff as to whether patients had a serious drug problem. Of the original 24 items, 14 SOAPP items appeared to predict subsequent aberrant behaviors. Coefficient alpha for these 14 items was acceptable for a short scale (0.74). Receiver operating characteristics curve analysis yielded an area under the curve of 0.881 (P<0.001), suggesting adequate sensitivity and specificity for a screening device. These reliability and predictive validity results suggest that the SOAPP is a promising step toward screening risk potential for substance misuse among persons with chronic pain.

Validation of the Spanish Addiction Severity Index Multimedia Version (S-ASI-MV).

This study aimed to develop and test the reliability and validity of a Spanish adaptation of the ASI-MV, a computer administered version of the Addiction Severity Index, called the S-ASI-MV. Participants were 185 native Spanish-speaking adult clients from substance abuse treatment facilities serving Spanish-speaking clients in Florida, New Mexico, California, and Puerto Rico. Participants were administered the S-ASI-MV as well as Spanish versions of the general health subscale of the SF-36, the work and family unit subscales of the Social Adjustment Scale Self-Report, the Michigan Alcohol Screening Test, the alcohol and drug subscales of the Personality Assessment Inventory, and the Hopkins Symptom Checklist-90. Three-to-five-day test-retest reliability was examined along with criterion validity, convergent/discriminant validity, and factorial validity. Measurement invariance between the English and Spanish versions of the ASI-MV was also examined. The S-ASI-MV demonstrated good test-retest reliability (ICCs for composite scores between .59 and .93), criterion validity (rs for composite scores between .66 and .87), and convergent/discriminant validity. Factorial validity and measurement invariance were demonstrated. These results compared favorably with those reported for the original interviewer version of the ASI and the English version of the ASI-MV.

Cross-Validation of a Screener to Predict Opioid Misuse in Chronic Pain Patients (SOAPP-R).

OBJECTIVES: The Screener and Opioid Assessment for Patients with Pain - Revised (SOAPP-R) is a self-report questionnaire designed to predict aberrant medication-related behaviors among persons with chronic pain. This measure was developed to complement current risk assessment practices and to improve a clinician's ability to assess a patient's risk for opioid misuse. The aim of this study was to cross-validate the SOAPP-R with a new sample of chronic, non-cancer pain patients. METHODS: Three hundred and two participants (N=302) prescribed opioids for pain were recruited from five pain management centers in the U.S. Subjects completed a series of self-report measures and were followed for five months. Patients were rated by their treating physician, had a urine toxicology screen, and were classified on the Aberrant Drug Behavior index. RESULTS: Seventy-three percent (73.2%) of the subjects (N= 221) were followed and 66 participants repeated the SOAPP-R after one week for test-retest reliability. The reliability and predictive validity, as measured by the area under the curve (AUC), were found to be highly significant (test-retest reliability = .91; coefficient alpha = .86; AUC = .74) and were sufficiently similar to values found with the initial sample. A cut-off score of 18 revealed a sensitivity of .80 and specificity of .52. CONCLUSIONS: Results of this cross-validation study suggest that the psychometric parameters of the SOAPP-R are not based solely on the unique characteristics of the initial validation sample. The SOAPP-R is found to be a reliable and valid screening tool for risk of aberrant drug-related behavior among chronic pain patients.

Does report of craving opioid medication predict aberrant drug behavior among chronic pain patients?

OBJECTIVE: To examine the relationship between the self-report of craving prescription medication and subsequent opioid misuse among chronic pain patients prescribed opioids for pain. METHODS: Six hundred thirteen patients taking opioid medication for chronic noncancer pain were asked how often they have felt a craving for their medication on a scale from 0=never to 4=very often. All participants completed a series of baseline questionnaires. After 6 months the participants were administered a structured prescription drug use interview (Prescription Drug Use Questionnaire), and submitted a urine sample for toxicology assessment. Their treating physicians also completed a substance misuse behavior checklist (Prescription Opioid Therapy Questionnaire). RESULTS: Three hundred thirty-seven participants (55.0%) reported that they never felt a craving for their medication, whereas 276 (45.0%) reported some degree of craving their medication (seldom to very often). Those who reported craving their medication were significantly more often male (P<0.01), unmarried (P<0.05), had lower scores on social desirability (P<0.001), and had been prescribed opioids for a longer time (P<0.05) than those who did not report craving medication. At 6-month follow-up, those who reported craving their medication showed higher scores on the Prescription Drug Use Questionnaire (P<0.001), had a higher incidence of physician-rated aberrant drug behavior on the Prescription Opioid Therapy Questionnaire (P<0.05), showed a higher frequency of abnormal urine toxicology screens (P<0.001), and more often had a positive Aberrant Drug Behavior Index (P<0.001). DISCUSSION: These results suggest that self-reported craving is a potential marker for identification of those at risk for opioid medication misuse.

Internet-based survey of nonmedical prescription opioid use in the United States.

INTRODUCTION: Prescription opioid misuse is a growing problem in the United States. There are limited data to illuminate the nature of this issue. The Internet seems to be a novel approach in surveying populations of opioid users. An Internet-based survey of nonmedical opioid users visiting informational drug websites was used to measure rates of nonmedical use and characterize users. METHODS: The prescription opioid module of the Addiction Severity Index Multimedia Version Connect was adapted to include variables such as favorite opioid. Links to the survey were posted on an informational drug website. Nonmedical use rates for KADIAN (morphine sulfate extended-release tablets), OxyContin (oxycodone HCl controlled-release tablets), Vicodin (hydrocodone bitartrate and acetaminophen tablets), and product-classes (morphine ER, oxycodone ER, and hydrocodone) were calculated. Descriptive statistics were calculated for remaining questions. RESULTS: During a 1-month recruitment period, 896 valid individuals completed the survey. Majority were white (78.3%) and male (72.4%). Participants were less likely to have used KADIAN in the past 30 days compared with OxyContin (P<0.0001) and Vicodin (P=0.0021). Additionally, participants were less likely to have used morphine ER in the previous 30 days than either oxycodone ER (P<0.0001) or hydrocodone (P<0.0001). Among OxyContin, Vicodin, and KADIAN users, OxyContin (43.8%), Dilaudid (15.6%), and fentanyl (9.4%) were the top 3 favorite opioids. DISCUSSION: This project demonstrates the feasibility of conducting product-specific, online surveys with rapid recruitment of participants from websites. This approach differentiates rates of nonmedical use of specific prescription opioids and provides other insights into individuals who nonmedically use opioids.

A pilot study of an online workplace nutrition program: the value of participant input in program development.

OBJECTIVE: Tailored nutrition Web programs constitute an emerging trend in obesity prevention. Initial investment in innovative technology necessitates that the target population be well understood. This pilot study's purpose was to determine the feasibility of a workplace nutrition Web program. DESIGN: Formative research was conducted with gaming industry employees and benefits managers to develop a consensus on workplace-specific nutrition needs. A demonstration Web program was piloted with stakeholders to determine feasibility. SETTING: Indiana, Mississippi, Nevada, and New Jersey gaming establishments. PARTICIPANTS: 86 employees, 18 benefits managers. INTERVENTION: Prototype Web program. MAIN OUTCOME MEASURES: Concept mapping; 16-item nutrition knowledge test; satisfaction. ANALYSIS: Concept mapping was used to aggregate importance ratings on programmatic content, which informed Web program curriculum. Chi-square tests were performed postintervention to determine knowledge improvement. RESULTS: (1) Employees and benefits managers exhibited moderate agreement about content priorities for the program (r = 0.48). (2) There was a significant increase in employees' nutrition knowledge scores postintervention (t = 7.16, df = 36, P < .001); those with less knowledge exhibited the greatest gains in knowledge scores (r = -0.647, P < .001). CONCLUSIONS AND IMPLICATIONS: Employees and benefit managers do not necessarily agree on the priority of nutrition-related content, suggesting a need for programs to appeal to various stakeholders. Computer-based approaches can address various stakeholder health concerns via tailored, customized programming.