Our Work
Can consumers self-select for appropriate use of an over-the-counter statin? The Self Evaluation of Lovastatin to Enhance Cholesterol Treatment Study
Brass EP, Vassil T, Replogle A, Hwang P, Rusche S, Shiffman S, Levine JG
Can consumers self-select for appropriate use of an over-the-counter statin? The Self Evaluation of Lovastatin to Enhance Cholesterol Treatment Study
Am J Cardiol. 2008 May 15;101(10):1448-55. Epub 2008 Mar 17.
ABSTRACT
Access to over-the-counter (OTC) statins has the potential to improve public health by reducing cardiovascular events. The Self Evaluation of Lovastatin to Enhance Cholesterol Treatment (SELECT) Study was designed to assess consumers’ ability to self-select for treatment with lovastatin in an unsupervised setting. Subjects examined proposed OTC lovastatin cartons with labels that detailed an algorithm for self-selection based on age, lipid profile, and cardiovascular risk factors. Subjects viewed a carton with either a low-density lipoprotein cholesterol-based self-selection algorithm or one based on total cholesterol. Labels also contained warnings against use based on health conditions that might increase the risk of adverse events. Subjects were asked if the drug was appropriate for their use (self-assessment) and whether they would like to purchase the drug (purchase decision). A total of 1,326 consumers provided self-assessment decisions. After viewing the low-density lipoprotein cholesterol-based label, 82%, 36%, and 82% of those who self-assessed that the drug was appropriate for their use were correct with respect to the age, lipid, and risk-factor criteria, respectively. Corresponding numbers for the total cholesterol algorithm were 85%, 50% and 75%. Almost 90% of women aged <55 years who evaluated the drug indicated the drug was not right for them, and women in this age group made up only 9% of the total group of subjects who believed the drug was appropriate for their use. The label was also effective in discouraging use by women who were or may become pregnant, consumers with liver disease, and those with potential drug interactions. In conclusion, SELECT showed that consumers could use an OTC drug label in an unsupervised setting to appropriately self-select for self-management of their cholesterol with lovastatin.
Consumer understanding of prescription drug information: An illustration using an antidepressant medication.
Shiffman S, Gerlach KK, Sembower M, Rohay JM
Consumer understanding of prescription drug information: An illustration using an antidepressant medication.
Annals Pharmacother 2011;45:452-458.
ABSTRACT
Background:
Patient education and warnings have emerged as prominent interventions for improving drug safety. As part of the provision of information and guidance on safe use of drugs, patients often receive multiple pieces of written information when they obtain a prescription medication, including a Food and Drug Administration (FDA)-mandated medication guide (MG), consumer medication information (CMI), and patient package insert (PPI).
Objective:
To determine whether patients understand the materials providing drug information and whether the materials convey the intended information.
Methods:
Fifty-two adults with a high school education or less were shown an actual (blinded) MG, CMI, and PPI for a marketed antidepressant medication. Comprehension was tested with methods used by the FDA to assess label comprehension for nonprescription products.
Results:
The majority of participants (88.2%) looked at all 3 pieces of information provided. The mean (SD) time spent reviewing the CMI was 5.2 (4.8) minutes (range 0-21.9), 16.5 (13.3) minutes for the PPI (range 0-43.0), and 2.5 (1.6) minutes for the MG (range 0-7.6). Less than 20% of participants were able to identify the symptoms of a rare but potentially life-threatening situation that can occur with this medication and only 61.5% recalled the risk of teen suicide, which is the sole focus of the MG. Respondents with lower literacy scores performed more poorly than those with higher literacy scores.
Conclusions:
Information provided with at least some prescription drugs is not adequately understood by less-educated consumers and does not effectively communicate critical safety messages or directions.
Consumers appropriately self-treat based on labeling for over-the-counter hydrocortisone
Ellis CN, Pillitteri J, Kyle TK, Ertischek MD, Burton SL, Shiffman S
Consumers appropriately self-treat based on labeling for over-the-counter hydrocortisone
J Am Acad Dermatol. 2005 Jul;53(1):41-51.
ABSTRACT
Background:
Over-the-counter (OTC) topical corticosteroids, such as hydrocortisone cream (HC), are commonly used for the treatment of minor dermatological conditions. The safety and efficacy of such products are well documented, but details on patterns of use and self-treatment with HC in the OTC environment remain scarce.
Objective:
We sought to determine compliance with label directions of OTC HCs by examining self-reported patterns of OTC HC use in adults and children.
Methods:
A random digit-dialed telephone survey was conducted with 2000 US adults. Following identification of users of OTC HC in the last 6 months, respondents were asked questions about the conditions being treated with OTC HC and the frequency and duration of use in both adults and children.
Results:
Of adults completing the survey, 20% (n = 396) had used OTC HC. In 83% of cases, the conditions treated were consistent with the OTC label. Use was limited; HC was applied < or =4 times daily in 98% of adult users and lasted < or =7 days in 92%. Patterns of pediatric use were similar and almost always consistent with the labeling. Of households with children, 25% (n = 168) had used OTC HC to treat pediatric dermatological conditions. Of child users, 93% were 2 years of age or older, treatment was limited (97% applied HC < or =4 times daily and 94% of treatments lasted < or =7 days), and the conditions treated were appropriate in 86% of cases.
Limitations:
This telephone survey relied on respondents’ recall and self-reporting. Our data on pediatric use of OTC HC are skewed toward treatment of younger children.
Conclusion:
The data suggest that OTC HC products are used for self-treatment in a limited and appropriate fashion that is likely to be safe in both adults and children.
Ten years after the Rx-to-OTC switch of nicotine replacement therapy: what have we learned about the benefits and risks of non-prescription availability?
Shiffman S, Sweeney CT
Ten years after the Rx-to-OTC switch of nicotine replacement therapy: what have we learned about the benefits and risks of non-prescription availability?
Health Policy, 2008 Apr;86(1):17-26. Epub 2007 Nov 1. Review
ABSTRACT
Objective:
Review the history of the Rx-to-OTC switch of nicotine replacement therapy (NRT) in the US, outlining concerns expressed before the switch, discussing how concerns were addressed, and presenting data on the actual experience in the decade following the switch.
Methods:
Literature review of studies examining trends in NRT utilization pre- and post-switch, the efficacy and safety of NRT in the OTC setting, and patterns of OTC NRT use.
Results:
OTC availability of NRT increased access to and utilization of treatment. Studies show that OTC NRT has been used safely and effectively, without substantial misuse or abuse, and with continued physician engagement and wide access to proven behavioral treatment.
Conclusions:
With other medications that challenge the traditional OTC paradigm being proposed for OTC switch, the NRT case study serves as a useful example in highlighting the potential role that Rx-to-OTC switch can play in addressing public health challenges. The NRT experience suggests that advance identification and analysis of concerns, implementation of plans to manage concerns, including appropriate marketing and post-marketing surveillance, can ensure that OTC switch of medications for behavior change and disease prevention can help minimize risks and maximize public health benefits.
The ALERRT® instrument: a quantitative measure of the effort required to compromise prescription opioid abuse-deterrent tablets.
Cone EJ, Buchhalter AR, Lindhardt K, Elhauge T, Dayno JM
The ALERRT® instrument: a quantitative measure of the effort required to compromise prescription opioid abuse-deterrent tablets.
Am J Drug Alcohol Abuse. 2017 May;43(3):291-298.
ABSTRACT
BACKGROUND:
US FDA guidance recommends measuring the degree of effort needed to manipulate abuse-deterrent (AD) opioids. The ALERRT® instrument (PinneyAssociates; Bethesda, MD) uses visual analog scales to assess the labor, effort, and resources necessary to physically compromise AD product candidates in standardized settings.
OBJECTIVE:
Use the ALERRT® instrument for testing morphine abuse-deterrent, extended-release, injection-molded tablets (ADER-IMT) 60 and 100 mg and the comparators immediate-release (IR) morphine sulfate 30 mg and extended-release (ER) morphine sulfate 60 mg.
METHODS:
Four technicians tested the products using 10 household tools. The ALERRT instrument quantified effort (all tools) and time (3 preselected tools) required for manipulation.
RESULTS:
Morphine-ADER-IMT 60 and 100 mg were difficult to manipulate, as demonstrated by high scores (mean range, 71.0-99.0 and 77.0-99.5, respectively). IR and ER morphine sulfate were easy to manipulate (low scores; mean range, 2.0-14.8 and 2.3-17.5, respectively). Statistically significant mean differences between morphine-ADER-IMT and comparators’ ALERRT scores were observed. Manipulations of morphine-ADER-IMT 60 and 100 mg for 300 seconds failed to produce substantial powdering. Manipulations of IR morphine sulfate (mean range, 65.5-175.8 seconds) and ER morphine sulfate (49.3-163.0 seconds) produced substantial to complete powdering in 92% of tablets.
CONCLUSIONS:
Morphine-ADER-IMT was extremely difficult to manipulate versus non-AD formulations of morphine. The ALERRT system differentiated the degree of effort for manipulation of morphine-ADER-IMT and non-AD morphine formulations, indicating sensitivity of this instrument as part of Category 1 testing. By measuring the degree of effort required for manipulation, the ALERRT instrument provides an empirical assessment into the relative difficulty of manipulating opioid analgesics for abuse.
Abuse potential assessment of novel opioid analgesic NKTR-181: implications for labeling and scheduling
Webster LR, Smith S, Silowsky J, Gogas K, Odinecs A, Eldon M, Abrouk N, Medve R, Henningfield JE, Buchhalter AR, Cone EJ, Fant RV, Schnoll S
Abuse potential assessment of novel opioid analgesic NKTR-181: implications for labeling and scheduling
CPDD. 2013.
ABSTRACT
The recent Draft FDA Guidance for Industry (Abuse-Deterrent Opioids Evaluation and Labeling) recognizes the need for safer opioids designed to deter abuse through their chemical structure. Current experience in the field has been with re-formulations of the drugs that are highly abused, hence the draft guidance does not provide specific consideration of new molecules with reduced abuse potential specifically engineered into the chemical structure. Since physical manipulation is not relevant in this setting, a new molecule with reduced abuse potential that is not subject to degradation or transformation of the chemical bonds to yield an abusable opioid may warrant an additional tier in the draft FDA guidance.
An iterative model for in vitro laboratory assessment of tamper deterrent formulations
Cone EJ, Giordano J, Weingarten B
An iterative model for in vitro laboratory assessment of tamper deterrent formulations
Drug Alcohol Depend 2013;131:100-5.
ABSTRACT
Background:
In an effort to address the continuing problem of prescription opioid abuse, manufacturers are incorporating new technologies into formulations that are designed to deter product tampering and misuse. Standards for laboratory assessment of tamper deterrent properties of new formulations have not previously been developed.
Methods:
Experimental designs were developed for the in vitro laboratory assessment of the tamper deterrent properties of reformulated oxycodone. Given that an exhaustive study of all potential tampering methods was impractical; this model was developed to evaluate the product in an incremental fashion with iterative changes that were amenable to objective and replicable laboratory testing.
Results:
A description of the model is provided along with pertinent examples involving assessment of reformulated oxycodone with comparisons to the original formulation. Physical and chemical procedures were developed that relate to “real-world” scenarios that may be applied to opioid formulations. Test results were interpreted in relation to the relative ease or difficulty of the manipulation as compared to control materials and the amount and purity of active drug that could be accessed. Results from some of the tests were designed to be useful in predicting whether specific tampering methods would facilitate or deter drug administration by different routes of administration.
Conclusions:
This model, developed to assess the tamper deterrent properties of reformulated oxycodone, should have application in the assessment of other drug formulations designed to exhibit tamper deterrence properties.
Do prescription monitoring programs impact state trends in opioid abuse/misuse?
Reifler LM, Droz D, Bailey JE, Schnoll S, Fant RV, Dart RC, Bucher Bartelson B
Do prescription monitoring programs impact state trends in opioid abuse/misuse?
Pain Med. 2012 Mar;13(3):434-42.
ABSTRACT
Objective:
Prescription monitoring programs (PMPs) are statewide databases containing prescriber and patient-level prescription data on select drugs of abuse. These databases are used by medical professionals or law enforcement officials to identify patients with prescription drug use patterns indicative of abuse or providers engaging in illegal activities. Most states have implemented PMPs in an attempt to curb prescription drug abuse and diversion. However, assessment of their impact on drug abuse is only beginning. This study aimed to evaluate the relationship between PMPs and opioid misuse over time in two drug abuse surveillance data sources.
Methods:
Data from the RADARS® System Poison Center and Opioid Treatment surveillance databases were used to obtain measures of abuse and misuse of opioids. Repeated measures negative binomial regression was applied to quarterly surveillance data (from 2003 to mid-2009) to estimate and compare opioid abuse and misuse trends. PMP presence was modeled as a time varying covariate for each state.
Results:
Results support an association between PMPs and mitigated opioid abuse and misuse trends. Without a PMP in place, Poison Center intentional exposures increased, on average, 1.9% per quarter, whereas opioid intentional exposures increase 0.2% (P = 0.036) per quarter with a PMP in place. Opioid treatment admissions increase, on average, 4.9% per quarter in states without a PMP vs 2.6% (P = 0.058) in states with a PMP. In addition to the time trend, population and a measure of drug availability were also significant predictors. A secondary analysis that classified PMP based upon ideal characteristic showed consistent though not significant results.
Conclusions:
Two observational data sources offer preliminary support that PMPs are effective. Future efforts should evaluate what PMP characteristics are most effective and which opioids are most impacted.
Epidemiology of stimulant misuse and abuse: implications for future epidemiologic and neuropharmacologic research
Gerlach KK, Dasgupta N, Schnoll S, Henningfield JE
Epidemiology of stimulant misuse and abuse: implications for future epidemiologic and neuropharmacologic research
Neuropharmacology. 2014 Dec;87:91-6
ABSTRACT
Stimulants are a diverse array of drugs that range from everyday caffeine to prescription medications and illicitly manufactured street drugs. The surveillance of misuse and abuse of stimulants many times confounds prescription and illicit street drugs such that the data are not specific enough to guide mitigation efforts or assess their impact. This review highlights the surveillance efforts that are conducted in the United States (US) for stimulant misuse and abuse. These surveillance efforts include national level surveys as well as reporting systems such as Poison Centers and emergency departments. This epidemiologic analysis has implications for interpreting the current known neuropharmacology of stimulants and possibly informing future neuropharmacology research that may contribute to a better understanding of potential neuropharmacologic factors influencing differing patterns of use, abuse, and adverse consequences associated with various stimulants. This article is part of the Special Issue entitled ‘CNS Stimulants’.
Establishing “abuse-deterrence equivalence” for generic abuse-deterrent opioid formulations: A proposed development framework
Setnik B, Cone EJ
Establishing “abuse-deterrence equivalence” for generic abuse-deterrent opioid formulations: A proposed development framework
J Opioid Manag. 2016 Mar-Apr;12(2):96-100.
ABSTRACT
Abuse-deterrent formulations are one strategy for mitigating the epidemic of prescription opioid abuse. Regulatory guidance documents describe the requirements for developing abuse-deterrent formulations of novel drugs and formulations; however, they do not address “abuse-deterrence equivalence” for generic formulations. As generics may be produced with different excipients and formulations compared to reference drugs, differences in their properties may impact their abuse-deterrent features. Currently, it is unclear what specific studies are needed to support generic abuse-deterrence claims. This commentary outlines several recommendations on the in vitro and in vivo testing required, including the conditions for conducting a human abuse potential study.
Extreme work requirement of EG-001, an abuse-deterrent, extended-release morphine product, as demonstrated with the ALERRT® Visual Analog Scales.
Cone EJ, Buchhalter AR, Lindhardt K, Elhauge T, Dayno JM
Extreme work requirement of EG-001, an abuse-deterrent, extended-release morphine product, as demonstrated with the ALERRT® Visual Analog Scales.
PainWeek. 2015.
ABSTRACT
The goal of this study was to measure the amount of “work” (ie, combination of time, effort, and resources) required to physically compromise the AD technology of EG-001 tablets compared with marketed formulations of immediate-release and extended release morphine using standardized manipulation techniques and a newly developed instrument, the Assessing Labor, Effort and Resources Required for Tampering scales (ALERRT tm; PinneyAssociates, Bethesda, MD), visual analog scales or VASs.
Nonmedical use of prescription ADHD stimulants and preexisting patterns of drug abuse
Sweeney CT, Sembower M, Ertischek MD, Shiffman S, Schnoll S
Nonmedical use of prescription ADHD stimulants and preexisting patterns of drug abuse
J Addict Dis. 2013;32(1):1-10.
ABSTRACT
Multidrug use is well documented among nonmedical users of prescription stimulants. We sought to provide insight into the drug use patterns of those reporting nonmedical use of prescription attention-deficit hyperactivity disorder (ADHD) stimulants in an attempt to discern whether such use is a first step in a pattern of drug-abusing behavior or, conversely, is a later development accompanied or preceded by a history of drug abuse. A cross-sectional, population-based survey of the U.S. civilian, non-institutionalized population aged 12 years and older was analyzed for lifetime nonmedical use of prescription ADHD stimulants, lifetime nonmedical use of another prescription drug, illicit drug use, and drug use initiation patterns. This included 443,041 respondents from the 2002-2009 National Survey on Drug Use and Health. Lifetime nonmedical use of prescription ADHD stimulants was reported by 3.4% of those aged 12 years and older. Of these, 95.3% also reported use of an illicit drug (i.e., marijuana, cocaine/crack, heroin, hallucinogens, inhalants) or nonmedical use of another prescription drug (i.e., tranquilizers, pain relievers, or sedatives), and such use preceded nonmedical use of prescription ADHD stimulants in 77.6% of cases. On average, 2.40 drugs were used prior to the first nonmedical use of prescription ADHD stimulants. These data suggest that nonmedical use of prescription ADHD stimulants is not commonly an initiating factor leading to the nonmedical use of other prescription medications or abuse of illicit drugs. Rather, nonmedical use of prescription ADHD stimulants appears to be adopted by individuals already engaged in broader patterns of drug abuse and misuse.
The new science of abuse-deterrence assessment of pharmaceutical products; FDA proposed guidance and Category 1 laboratory studies
Cone EJ, Buchhalter AR, Henningfield JE, Schnoll S
The new science of abuse-deterrence assessment of pharmaceutical products; FDA proposed guidance and Category 1 laboratory studies
Pharm Anal Acta. 2014; 5(9): 317.
ABSTRACT
The problem of prescription drug abuse in the United States began more than 100 years ago and became
epidemic in the last decade producing many tragic consequences with incredible societal costs. Drug overdoses have doubled over the last 10 years and now surpass deaths from motor vehicle accidents (DHHS, 2013). Congress reacted to this ongoing tragedy in 2012 by mandating the Food and Drug Administration (FDA) promulgate guidelines for the development of abuse-deterrent formulations (ADFs) for prescription opioid medications as one of the approaches to reducing this problem.The FDA responded in 2013 by issuing a draft guidance to industry for assessment of ADFs (FDA, 2013). The 2013 guidance expanded initial guidance proposed in 2010 (FDA, 2010).FDA is expected to issue final guidance for industry in the latter part of 2014.