State Laws and Legislation Related to Biologic Medications and Substitution of Biosimilars
Source: National Conference of State Legislatures
For several decades, every state has regulated the use of brand-name and generic prescription drugs through statutes and agency or board rules. These state actions include when and how generics may be substituted for brand-name prescriptions, by pharmacists or others. Generic drugs typically have active ingredients that are identical to those of their brand-name counterpart. These traditional drugs include familiar pills used regularly by tens of millions of Americans as well as some specialty drugs.
Biologic medicines are much more complex than traditional chemically synthesized drugs. Biologics are manufactured from living organisms by programming cell lines to produce the desired therapeutic substances and consist of large molecules. Common biologics in use today include human growth hormone, injectable treatments for arthritis and psoriasis, the Hepatitis B vaccine and stem cell therapy.
Regulating biologics raises new issues for both state and federal policymakers. Because of their complexity, biologic drugs are much more difficult to replicate than the chemically produced generics for other drugs. The cell lines used and modifications in the manufacturing process affect biologic medicines. As a result, truly identical “generic” versions are currently virtually impossible to produce. However, once patents expire for the existing brand-name biologic drugs, “biosimilar” medicines can be produced, which is an occurrence that raises regulatory issues in the states.
Currently, there is concern that traditional statutes regulating “generic drugs” may be misapplied to new products that are not identical. This has led to a recent move to amend older state laws to address the medical and chemical characteristics of these “biologics,” as well as any future generic-style “follow-on biologics” or “biosimilars.”
In the past one and a half years at least 23 states have considered legislation establishing state standards for substitution of a “biosimilar” prescription product to replace an original biologic product.
Use of St. John’s Wort in Potentially Dangerous Combinations
Source: Journal of Alternative and Complementary Medicine
The objective of this study was to assess how often St. John’s wort (SJW) is prescribed with medications that may interact dangerously with it.
The study design was a retrospective analysis of nationally representative data from the National Ambulatory Medical Care Survey.
The study setting was U.S. nonfederal outpatient physician offices.
Those prescribed SJW between 1993 and 2010 were the subjects.
The outcome measures were medications co-prescribed with SJW.
Results: Twenty-eight percent (28%) of SJW visits involved a drug that has potentially dangerous interaction with SJW. These included selective serotonin reuptake inhibitors, benzodiazepines, warfarin, statins, verapamil, digoxin, and oral contraceptives.
SJW is frequently used in potentially dangerous combinations. Physicians should be aware of these common interactions and warn patients appropriately.
NCPDP Recommendations and Guidance for Standardizing the Dosing Designations on Prescription Container Labels of Oral Liquid Medications
NCPDP Recommendations and Guidance for Standardizing the Dosing Designations on Prescription Container Labels of Oral Liquid Medications (PDF)
Source: National Council for Prescription Drug Programs
This paper provides the healthcare industry, in particular the pharmacy sector, with historical and background information on the patient risks associated with the dosing of liquid medications and recommendations to mitigate those risks through best practices in prescription orders, prescription labeling and the provision of dosing devices.
Decline in Drug Overdose Deaths After State Policy Changes — Florida, 2010–2012
Source: Morbidity and Mortality Weekly Report (CDC)
During 2003–2009, the number of deaths caused by drug overdose in Florida increased 61.0%, from 1,804 to 2,905, with especially large increases in deaths caused by the opioid pain reliever oxycodone and the benzodiazepine alprazolam (1). In response, Florida implemented various laws and enforcement actions as part of a comprehensive effort to reverse the trend. This report describes changes in overdose deaths for prescription and illicit drugs and changes in the prescribing of drugs frequently associated with these deaths in Florida after these policy changes. During 2010–2012, the number of drug overdose deaths decreased 16.7%, from 3,201 to 2,666, and the deaths per 100,000 persons decreased 17.7%, from 17.0 to 14.0. Death rates for prescription drugs overall decreased 23.2%, from 14.5 to 11.1 per 100,000 persons. The decline in the overdose deaths from oxycodone (52.1%) exceeded the decline for other opioid pain relievers, and the decline in deaths for alprazolam (35.6%) exceeded the decline for other benzodiazepines. Similar declines occurred in prescribing rates for these drugs during this period. The temporal association between the legislative and enforcement actions and the substantial declines in prescribing and overdose deaths, especially for drugs favored by pain clinics, suggests that the initiatives in Florida reduced prescription drug overdose fatalities.
No Time to Waste: Evidence-Based Treatment for Drug Dependence at the United States Veterans Administration Department of Veterans Affairs
The 39-page report states that more than one million US veterans take prescription opioids for pain, and nearly half of them use the drugs “chronically,” or beyond 90 days. Alcohol and drug dependence is strongly associated with homelessness and mental health conditions including post-traumatic stress syndrome and depression, psychological conditions that affect 40 percent of Iraq and Afghanistan veterans in VA care. Drugs or alcohol are involved in 1 of 3 Army suicides, and the VA estimates that 22 veterans commit suicide each day.
Vital Signs: Variation Among States in Prescribing of Opioid Pain Relievers and Benzodiazepines — United States, 2012
Vital Signs: Variation Among States in Prescribing of Opioid Pain Relievers and Benzodiazepines — United States, 2012
Source: Morbidity and Mortality Weekly Report (CDC)
Overprescribing of opioid pain relievers (OPR) can result in multiple adverse health outcomes, including fatal overdoses. Interstate variation in rates of prescribing OPR and other prescription drugs prone to abuse, such as benzodiazepines, might indicate areas where prescribing patterns need further evaluation.
CDC analyzed a commercial database (IMS Health) to assess the potential for improved prescribing of OPR and other drugs. CDC calculated state rates and measures of variation for OPR, long-acting/extended-release (LA/ER) OPR, high-dose OPR, and benzodiazepines.
Results: In 2012, prescribers wrote 82.5 OPR and 37.6 benzodiazepine prescriptions per 100 persons in the United States. State rates varied 2.7-fold for OPR and 3.7-fold for benzodiazepines. For both OPR and benzodiazepines, rates were higher in the South census region, and three Southern states were two or more standard deviations above the mean. Rates for LA/ER and high-dose OPR were highest in the Northeast. Rates varied 22-fold for one type of OPR, oxymorphone.
Factors accounting for the regional variation are unknown. Such wide variations are unlikely to be attributable to underlying differences in the health status of the population. High rates indicate the need to identify prescribing practices that might not appropriately balance pain relief and patient safety.
Implications for Public Health:
State policy makers might reduce the harms associated with abuse of prescription drugs by implementing changes that will make the prescribing of these drugs more cautious and more consistent with clinical recommendations.
Drug Safety in the Digital Age
Source: New England Journal of Medicine
In this digital age, engaging with new media offers an unparalleled opportunity for medical and public health professionals to find information they need and to interactively reach out to patients and their support networks. One domain where these capabilities may have far-reaching effects that are currently undefined is drug safety. As the volume of health-related information on the Internet has grown, important questions have emerged. How are messages from regulators — for example, warnings against using a drug in a specific patient population — diffused digitally? And are the messages still accurate when they reach the general population?
Despite debates over its credibility, Wikipedia is reportedly the most frequently consulted online health care resource globally: Wikipedia pages typically appear among the top few Google search results and are among the references most likely to be checked by Internet users. We therefore evaluated Google searches and Wikipedia page views for each drug in our sample. We also examined the content of Wikipedia pages, looking specifically for references to safety warnings. To control for secular trends, we examined results from a 120-day window around the date of the announcement (from 60 days before the announcement to 60 days after it) and constructed a baseline period for comparison that ran from 60 days to 10 days before the period of interest began.
We identified safety warnings for 22 prescription drugs that are indicated for a range of clinical conditions, including primary hypertension, chronic myelogenous leukemia, and hepatitis C. Collectively, these drugs triggered 13 million searches on Google and 5 million Wikipedia page views annually during the study period. FDA safety warnings were associated with an 82% increase, on average, in Google searches for the drugs during the week after the announcement and a 175% increase in views of Wikipedia pages for the drugs on the day of the announcement, as compared with baseline trends.
Did users find accurate information on the drugs’ safety? We found that 41% of Wikipedia pages pertaining to the drugs with new safety warnings were updated within 2 weeks after the warning was issued with information provided in the FDA announcements. The Wikipedia pages for drugs that were intended for treatment of highly prevalent diseases (affecting more than 1 million people in the United States) were more likely to be updated quickly (58% were updated within 2 weeks) than were those for drugs designed to treat less-prevalent conditions (20% were updated within 2 weeks, P=0.03; see Fig. S2 in the Supplementary Appendix).
Overall, 23% of Wikipedia pages were updated more than 2 weeks after the FDA warning was issued (average, 42 days), and 36% of pages remained unchanged more than 1 year later (as of January 2014). For example, the FDA issued a safety communication on January 13, 2012, that brentuximab vedotin (Adcetris), used to treat Hodgkin’s lymphoma and systemic anaplastic large-cell lymphoma, had been linked to two cases of progressive multifocal leukoencephalopathy. As a result, the FDA placed a new black-box warning about this risk on the drug label, a move that was followed by a 50% increase in Google searches for the drug during the ensuing week and a 141% increase in views of the drug’s Wikipedia page. However, there was still no mention of the new black-box warning on Wikipedia 2 years later, a discrepancy that substantiates concerns raised by previous studies over the reliability of online drug information.
New GAO Reports
Source: Government Accountability Office
1. Climate Change Adaptation: DOD Can Improve Infrastructure Planning and Processes to Better Account for Potential Impacts. GAO-14-446, May 30.
Highlights - http://www.gao.gov/assets/670/663733.pdf
2. Prescription Drugs: Comparison of DOD, Medicaid, and Medicare Part D Retail Reimbursement Prices. GAO-14-578, June 30.
Highlights - http://www.gao.gov/assets/670/664522.pdf
3. Nuclear Security: NNSA Should Establish a Clear Vision and Path Forward for Its Security Program. GAO-14-208,May 30.
Highlights - http://www.gao.gov/assets/670/663746.pdf
FDA outlines expectations for human drug compounders, including registered outsourcing facilities
Source: U.S. Food and Drug Administration
Today, the U.S. Food and Drug Administration issued several policy documents regarding compounded drug products for human use, as part of the agency’s continuing effort to implement the compounding provisions of the Drug Quality and Security Act (DQSA), enacted in November 2013. The policy documents consist of a draft interim guidance, a proposed rule, a final guidance, and two revised requests for nominations for the bulk drug substances lists.
“Providing clarity to the compounding industry on the agency’s expectations for these unapproved drug products is a priority for the agency,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. “These actions are essential next steps in providing the compounding industry with the appropriate tools to comply with the law and advancing the FDA’s efforts to continue protecting patients.”
New Older Driver Data Trends in Upward Direction
Source: AAA Foundation for Traffic Safety
According to a new report from the AAA Foundation for Traffic Safety, older Americans are extending their time behind the wheel compared to previous generations. For example, 84 percent of Americans 65 and older held a driver’s license in 2010 compared to barely half in the early 1970s. Today, one in six drivers on U.S. roads are ages 65 and older and this new research shows an increased automobility of older drivers with travel patterns indicating about a 20 percent increase in trips and a 33 percent increase in miles travelled between 1990 and 2009.
While upward trends indicate greater mobility for the silver tsunami, the Understanding Older Drivers: An Examination of Medical Conditions, Medication Use and Travel Behaviors report reveals that 90 percent of older drivers also use prescription medications with two-thirds taking multiple medications. Previous Foundation research has shown that combinations of medications, both prescription and over- the-counter, can result in an impairment in safe driving ability.
The report also reveals gender differences when it comes to medication-use behind the wheel. Older women that use medications are more likely to regulate their driving compared to men and, even without a medical condition, female drivers drive less than their male counterparts with a medical condition.
Metabolic syndrome among psychiatric outpatients with mood and anxiety disorders
Source: BMC Psychiatry
Few studies have simultaneously compared the impacts of pharmacotherapy and mental diagnoses on metabolic syndrome (MetS) among psychiatric outpatients with mood and anxiety disorders. This study aimed to investigate the impacts of pharmacotherapy and mental diagnoses on MetS and the prevalence of MetS among these patients.
Two-hundred and twenty-nine outpatients (men/women = 85/144) were enrolled from 1147 outpatients with mood and anxiety disorders by systematic sampling. Psychiatric disorders and MetS were diagnosed using the Structured Clinical Interview for DSM-IV-TR and the new International Diabetics Federation definition, respectively. The numbers of antipsychotics, mood stabilizers, and antidepressants being taken were recorded. Logistic regression was used to investigate the impacts of pharmacotherapy and psychiatric diagnoses on MetS.
Among 229 subjects, 51 (22.3%) fulfilled the criteria for MetS. The prevalence of MetS was highest in the bipolar I disorder (46.7%) patients, followed by bipolar II disorder (25.0%), major depressive disorder (22.0%), anxiety-only disorders (16.7%), and no mood and/or anxiety disorders (14.3%). The percentages of MetS among the five categories were correlated with those of the patients being treated with antipsychotics and mood stabilizers. Use of antipsychotics and/or mood stabilizers independently predicted a higher risk of MetS after controlling for demographic variables and psychiatric diagnoses. When adding body mass index (BMI) as an independent variable in the regression model, BMI became the most significant factor to predict MetS.
BMI was found to be an important factor related to MetS. Pharmacotherapy might be one of underlying causes of elevated BMI. The interactions among MetS, BMI, pharmacotherapy, and psychiatric diagnoses might need further research.
An analysis of 20 years of Cigna’s short-term disability claims shows that absence related to obesity, treatment for skin cancer and herniated disc surgery increased significantly from 1993 to 2012, while a reduction in absences related to depression coupled with an increase in prescribed anti-depressants may signal a hidden problem. These and other health trends identified by the analysis are important for employers to understand when structuring an integrated wellness and absence management program to improve workforce productivity.
Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coverage: quasi-experimental study
To investigate if the widely publicized warnings in 2003 from the US Food and Drug Administration about a possible increased risk of suicidality with antidepressant use in young people were associated with changes in antidepressant use, suicide attempts, and completed suicides among young people.
Quasi-experimental study assessing changes in outcomes after the warnings, controlling for pre-existing trends.
Automated healthcare claims data (2000-10) derived from the virtual data warehouse of 11 health plans in the US Mental Health Research Network.
Study cohorts included adolescents (around 1.1 million), young adults (around 1.4 million), and adults (around 5 million).
Main outcome measures
Rates of antidepressant dispensings, psychotropic drug poisonings (a validated proxy for suicide attempts), and completed suicides.
Trends in antidepressant use and poisonings changed abruptly after the warnings. In the second year after the warnings, relative changes in antidepressant use were −31.0% (95% confidence interval −33.0% to −29.0%) among adolescents, −24.3% (−25.4% to −23.2%) among young adults, and −14.5% (−16.0% to −12.9%) among adults. These reflected absolute reductions of 696, 1216, and 1621 dispensings per 100 000 people among adolescents, young adults, and adults, respectively. Simultaneously, there were significant, relative increases in psychotropic drug poisonings in adolescents (21.7%, 95% confidence interval 4.9% to 38.5%) and young adults (33.7%, 26.9% to 40.4%) but not among adults (5.2%, −6.5% to 16.9%). These reflected absolute increases of 2 and 4 poisonings per 100 000 people among adolescents and young adults, respectively (approximately 77 additional poisonings in our cohort of 2.5 million young people). Completed suicides did not change for any age group.
Safety warnings about antidepressants and widespread media coverage decreased antidepressant use, and there were simultaneous increases in suicide attempts among young people. It is essential to monitor and reduce possible unintended consequences of FDA warnings and media reporting.
More than 100 New Medicines in Development to Treat Mental and Addictive Disorders
Source: Pharmaceutical Research and Manufacturers of America (PhRMA)
America’s biopharmaceutical research companies currently are developing 119 novel new medicines to help improve the lives of the estimated 61.5 million Americans that are affected by mental health disorders, according to a new report by the Pharmaceutical Research and Manufacturers of America (PhRMA).
These medicines in development – all either in clinical trials or under review by the Food and Drug Administration (FDA) – include 36 for schizophrenia, 29 for depression, 20 for substance/addictive disorders, 15 for attention deficit/hyperactivity disorder and 15 for anxiety disorders.
Mental health conditions pose a heavy human and economic burden in the United States. According to the National Institute of Mental Health (NIMH), 1 in 4 American adults have been diagnosed with a mental health disorder – and serious mental illnesses cost the U.S. more than $317 billion annually in lost wages, health care expenditures and disability benefits.
Combined Assessment Program Summary Report – Evaluation of the Controlled Substances Inspection Program at Veterans Health Administration Facilities
Combined Assessment Program Summary Report – Evaluation of the Controlled Substances Inspection Program at Veterans Health Administration Facilities (PDF)
Source: U.S. Department of Veterans Affairs, Office of Inspector General
The purpose of the review was to determine whether Veterans Health Administration (VHA) facilities complied with requirements related to controlled substances (CS) security and inspections and to follow up on the OIG report Healthcare Inspection – Review of Selected Pharmacy Operations in Veterans Health Administration Facilities (Report No. 07-03524-40, December 3, 2009). OIG performed this review in conjunction with 58 Combined Assessment Program reviews of VHA medical facilities conducted from October 1, 2012, through September 30, 2013. OIG identified opportunities for improvement in: conducting annual physical security surveys and correcting identified deficiencies; completing quarterly trend reports and providing them to facility Directors; conducting monthly CS inspections of non-pharmacy areas; completing non-pharmacy inspection activities; performing emergency drug cache quarterly physical counts and monthly verification of seals; validating completion of required drug destruction activities, accountability of prescription pads stored in the pharmacy, and outpatient pharmacy written prescriptions for schedule II drugs; providing annual CS inspector training. VHA can strengthen policy by defining acceptable reasons for missed CS area inspections and providing guidance on CS Coordinator performance of monthly inspections. OIG made 10 recommendations.
An Analysis of Exchange Plan Benefits for Certain Medicines
Source: Pharmaceutical Research and Manufacturers of America (PhRMA)
A central goal of the Affordable Care Act (ACA) was to expand access to insurance so patients, particularly those with chronic disease, could access the treatments and medicines they need. Recognizing that coverage would have limited value without basic access and affordability, the ACA included a non-discrimination provision, an out-of-pocket spending cap, mandatory coverage of “essential health benefits,” and financial assistance for low-income enrollees.
Health insurers typically design “tiered” prescription drug benefits in which a patient’s cost varies depending on a drug’s tier placement (e.g., preferred, non-preferred, etc.). Tiering structures are therefore critical factors in affordability. Plans submit their formulary tiering structure, along with other aspects of the plan’s design, for review by the appropriate state or federal regulator to ensure they meet relevant requirements under the ACA.
Following a recent report that some exchange plans have placed all covered HIV/AIDS medicines on the highest tier, PhRMA engaged Avalere Health to determine the prevalence of such practices, which would appear to be at odds with the patient protections at the core of the ACA. Formularies that require high cost sharing for all medicines of a specific therapeutic type or “class” (e.g., insulins, statins, etc.) create access barriers for patients.
Prescription Drug Abuse (PDF)
Source: Congressional Research Service (via National Association of Chain Drug Stores)
An estimated 6.8 million individuals currently abuse prescription drugs in the United States. Unlike policy on street drugs, federal policy on prescription drug abuse is complicated by the need to maintain access to prescription controlled substances (PCS) for legitimate medical use. The federal government has several roles in reducing prescription drug abuse.
Outbreaks of Infections Associated With Drug Diversion by US Health Care Personnel (PDF)
Source: Mayo Clinic Proceedings
To summarize available information about outbreaks of infections stemming from drug diversion in US health care settings and describe recommended protocols and public health actions.
Patients and Methods
We reviewed records at the Centers for Disease Control and Prevention related to outbreaks of infections from drug diversion by health care personnel in US health care settings from January 1, 2000, through December 31, 2013. Searches of the medical literature published during the same period were also conducted using PubMed. Information compiled included health care setting(s), infection type(s), specialty of the implicated health care professional, implicated medication(s), mechanism(s) of diversion, number of infected patients, number of patients with potential exposure to blood-borne pathogens, and resolution of the investigation.
We identified 6 outbreaks over a 10-year period beginning in 2004; all occurred in hospital settings. Implicated health care professionals included 3 technicians and 3 nurses, one of whom was a nurse anesthetist. The mechanism by which infections were spread was tampering with injectable controlled substances. Two outbreaks involved tampering with opioids administered via patient-controlled analgesia pumps and resulted in gram-negative bacteremia in 34 patients. The remaining 4 outbreaks involved tampering with syringes or vials containing fentanyl; hepatitis C virus infection was transmitted to 84 patients. In each of these outbreaks, the implicated health care professional was infected with hepatitis C virus and served as the source; nearly 30,000 patients were potentially exposed to blood-borne pathogens and targeted for notification advising testing.
These outbreaks revealed gaps in prevention, detection, and response to drug diversion in US health care facilities. Drug diversion is best prevented by health care facilities having strong narcotics security measures and active monitoring systems. Appropriate response includes assessment of harm to patients, consultation with public health officials when tampering with injectable medication is suspected, and prompt reporting to enforcement agencies.
See also press release: CDC Report: Patients Harmed After Health Care Providers Steal Patients’ Drugs