Rates of genetic testing in patients prescribed drugs with pharmacogenomic information in FDA-approved labeling.

This study examined rates of genetic testing in two cohorts of publicly insured individuals who have newly prescribed medication with FDA pharmacogenomic labeling guidance. Genetic testing was rare (4.4% and 10.5% in Medicaid and Medicare cohorts, respectively) despite the fact that all participants selected were taking medications that contained pharmacogenomic labeling information. When testing was conducted it was typically done before the initial use of a target medication. Factors that emerged as predictors of the likelihood of undergoing genetic testing included White ethnicity (vs. Black), female gender, and age. Cost analyses indicated higher expenditures in groups receiving genetic testing vs. matched comparators with no genetic testing, as well as disparities between proactively and reactively tested groups (albeit in opposite directions across cohorts). Results are discussed in terms of the possible reasons for the low base rate of testing, mechanisms of increased cost, and barriers to dissemination and implementation of these tests.

PARC report: a perspective on the state of clinical pharmacogenomics testing.

In this Perspective, the authors discuss the state of pharmacogenomics testing addressing a number of advances, challenges and barriers, including legal ramifications, changes to the regulatory landscape, coverage of testing and the implications of direct-to-consumer genetic testing on the provision of care to patients. Patient attitudes toward pharmacogenomics testing and associated costs will play an increasingly important role in test acquisition and subsequent utilization in a clinical setting. Additional key steps needed include: further research trials demonstrating clinical utility and cost-effectiveness of pharmacogenetic testing, evidence review to better integrate genomic information into clinical practice guidelines in target therapeutic areas to help providers identify patients that may benefit from pharmacogenetic testing and engagement with payers to create a path to reimbursement for pharmacogenetic tests that currently have sufficient evidence of clinical utility. Increased adoption of testing by payers and improved reimbursement practices will be needed to overcome barriers, especially as the healthcare landscape continues to shift toward a system of value-based care.

Labeling Changes and Costs for Clinical Trials Performed Under the US Food and Drug Administration Pediatric Exclusivity Extension, 2007 to 2012.

Importance: Pharmaceutical manufacturers can receive 6 additional months of market exclusivity for performing pediatric clinical trials of brand-name drugs widely used in adults. Congress created this incentive in 1997 because these drugs were being used off-label in children without such trials. Objective: To review updates to drug labeling and the cost to consumers of extending market exclusivity related to the pediatric exclusivity program. Design: From government records, we identified 54 drugs that earned the pediatric exclusivity incentive between 2007 and 2012. We evaluated labeling changes from the pediatric studies. We then extracted trial details from clinical review documents and used industry estimates of trial costs on a per-patient basis to estimate cost of investment for trials (with a 10% cost of capital). To calculate the net return and cost to consumers during the 6-month exclusivity period, we estimated additional revenue for the 48 drugs with available information. Main Outcomes and Measures: For each drug, we evaluated labeling changes and costs associated with pediatric trials under the Best Pharmaceuticals for Children Act and the cost to consumers of 6-month market exclusivity extensions. Results: The 141 trials in our sample enrolled 20 240 children (interquartile range [IQR], 2-3 trials and 127-556 patients per drug). These trials led to 29 extended indications and 3 new indications, as well as new safety information for 16 drugs. Median cost of investment for trials was $36.4 million (IQR, $16.6 to $100.6 million). Among 48 drugs with available financial information, median net return was $176.0 million (IQR, $47.0 million to $404.1 million), with a median ratio of net return to cost of investment of 680% (IQR, 80% to 1270%). Conclusions and Relevance: Clinical trials conducted under the US Food and Drug Administration's pediatric exclusivity program have provided important information about the effectiveness and safety of drugs used in children. The costs to consumers have been high, exceeding the estimated costs of investment for conducting the trials. As an alternative, policymakers should consider direct funding of such studies.

Conformity of package inserts information to regulatory requirements among selected branded and generic medicinal products circulating on the East African market.

BACKGROUND: Availability of correct and adequate information about medicines is an important aspect in ensuring rational use of medicines and hence facilitating safety and expected efficacy of medicines during therapy. Package inserts have proven to be a good source of information to the prescribers and patients whereby they have been useful in highlighting important information pertaining proper use and handling of the medicines. The present study was aimed at establishing the extent to which package inserts of medicines circulating on the markets of the East African Community (EAC) Partner States conform to medicines information requirements as established in the harmonized guidelines as well as national guidelines. METHODS: A total of 99 package inserts from six (6) types of medicines namely Albendazole, Artemether/Lumefantrine (ALu), Ciprofloxacin, Paracetamol, Amoxicillin and Metronidazole were purposefully collected from three EAC Partner States: Kenya, Tanzania and Uganda. The medicines were selected based on their indications as first line treatments, high rates of utilization within the medicines supply system and their positions in treatment of diseases of public importance across EAC Partner States. The inserts were evaluated on the availability of information regarding fifteen (15) parameters as extracted from the EAC harmonized guidelines for registration of medicines. Moreover, comparisons were made between the percentage conformity of the branded versus generic products, markets from which the samples were collected, origin of the manufacturer and type of medicine. RESULTS: Majority (93.9-100%) of the medicines' package inserts highly conformed to the inclusion of the information regarding the description and composition of the medications, indications, dosage and methods of administration, warnings and precautions, contraindications and storage conditions. However, the information on handling and disposal, container package description, excipients used, clinical pharmacology of the medicines, and directions regarding overdose ranked the least in conformance with conformity ranging from 13.1-52.5%. The parameter with the lowest observed percentage conformity among the branded products scored 50% as compared to 10.8% among the generic products. Moreover, there was no significant difference (P<0.05) in the percentage conformity of the package inserts collected from each of the three Partner States as compared to the average from studied medicines. A generally good conformity was observed among medicines manufactured by European based manufacturers as compared to those based in Asia and EAC Partner States. In addition, PIs of Albendazole, Ciprofloxacin, Amoxicillin and Artemether/Lumefantrine did show overall high conformity across most of the product information requirements. CONCLUSION: Our study revealed the existence of a significant number of medicinal products circulating on the markets of EAC Partner States without necessary compliance with all product information requirements. We therefore recommend that NMRAs ensure thorough pre-market assessment of product information as well as strengthening their post marketing surveillance to ensure that medicines circulating on the market comply to medicines information requirements at all times. Emphasis should also be given to manufacturers on the importance of inclusion of appropriate and adequate product information for the safety of patients, including advocating for inclusion of patient-friendly and easy to understand medicines information.

The Japanese Postmarketing Adverse Event Relief System: A Confluence of Regulatory Science, the Legal System, and Clinical Pharmacology.

The Japanese Postmarketing Relief System provides for compensation to patients with adverse reactions, based on the acknowledgment that unpredicted adverse events occur inevitably once a drug is marketed. The system also provides new knowledge about the benefit-risk profile of a drug that may be incorporated into product labeling. The system relies on causality assessments that are based on sound clinical pharmacology principles. The system may serve as a model for other countries' healthcare systems.

The economics of polypharmacology: fixed dose combinations and drug cocktails.

The history of Fixed Dose Combination (FDC) oral drug products has been tumultuous over its history. Some FDCs were prepared for marketing purposes and others for clinical improvements. Often, the products prepared for marketing advantage ended up causing negative outcomes. However, in recent years, there has been a resurgence of FDCs as clinicians have found them adventitious for treatment of AIDS/HIV and for oral contraceptives, just to name two examples. International regulatory Agencies and most major drug regulatory agencies have established guidelines along with regulations concerning preparation, labeling and marketing for FDCs. The advantages of FDCs are said to be in the clinical realm where simplified therapy regimens are thought to enhance patient's medication taking compliance. On the financial side, health insurers and other payers normally save money from a decreased number of dispensing fees, the use of fewer bottles, labels, etc., and from the possible situation where the price of the FDC is less than the medication price of the two separate ingredients dispensed individually. Overall, there is a great deal of evidence in favor of appropriate FDCs.

Measuring the patient health, societal and economic benefits of US pediatric therapeutics legislation.

Through at least the mid-1990s, children were often referred to as 'therapeutic orphans' for whom many treatments were administered without the benefit of appropriate studies to guide drug labeling for dosing and other critical therapeutic decisions. At that time, there were no incentives for manufacturers to pursue such work, nor regulatory requirements to compel these studies. Congress addressed this by including an important provision titled the Best Pharmaceuticals for Children Act (BPCA) in the 1997 Food and Drug Administration Modernization and Accountability Act. This was complemented by another key piece of legislation, the Pediatric Research Equity Act (PREA) in 2003. The former Act and its successors created an incentive for firms to study on-patent drugs in pediatric populations by extending the market exclusivity of a medicine by 6 months. The latter was a requirement that provided the US FDA with the authority to require studies of drugs in children if an adult indication also occurs in children. In the current paper, we consider the effects of both pieces of legislation in terms of the health, societal, and economic benefits they have likely imparted and will continue to provide in the future. We conclude that the gains have been substantial - both in terms of safer and more effective use of medicines in children and in terms of new research that has been incentivized by the BPCA exclusivity provision. We estimate the gross economic benefits from the latter alone to be approximately $US360 billion.

The impact of federal warnings on publically funded desmopressin utilization among children in Ontario.

OBJECTIVE: To determine whether safety warnings issued by health regulatory agencies regarding desmopressin treatment influenced treatment rates among children. PATIENT POPULATION AND METHODS: We conducted a time-series analysis using health administrative data from Ontario, Canada, between January 1, 2003 and March 31, 2010. We examined desmopressin prescribing rates among children (<13 years) and investigated the impact of a United States Food and Drug Administration warning (December 2007) and a subsequent Health Canada warning (July 2008) on these rates. A secondary analysis stratified rates according to route of administration. RESULTS: On average, quarterly desmopressin treatment rates were 29.8% lower following the two warnings (4.7 per 1000 population) compared with the period prior to warnings being issued (6.7 per 1000 population). Structural break analyses identified a significant decrease in overall desmopressin prescribing rates in Q3 2008, with the 95% confidence interval (CI) spanning both safety warnings (Q4 2007 to Q1 2009). A secondary analysis of prescribing rates for oral formulations found consistent results (structural break Q4 2008, 95% CI Q2 2007 to Q2 2009). The average quarterly prescribing rate of intranasal formulations declined by 73.1% following the warnings compared with the period preceding the warnings. CONCLUSION: Safety warnings issued by regulatory agencies dramatically influenced desmopressin use among Ontario's children.

Investigation of RFID tag readability for pharmaceutical products at item level.

BACKGROUND: The applications of radio frequency identification (RFID) technology carry a tremendous potential for pharmaceutical industry. There is a pressing need to analyze the performance of RFID tags attached to various pharmaceutical dosage forms. METHOD: The readability of RFID-tagged pharmaceutical products is, for the first time, systematically investigated by experiments. Factors considered include dosage forms, ion concentration in solution, angle of rotation, and distance between the RFID tag and the interrogator. RESULTS: Compared with empty container, the filling of any representative dosage forms causes deteriorated readability for the tag attached to container. Analysis of variance reveals that the effects of dosage forms, angle of rotation, and their interaction are statistically significant. In addition, an increase in distance (equivalent to higher RF attenuation level) and higher ion concentration in solution beyond a certain level have detrimental effect on tag readability. CONCLUSION: The analysis shows that the RFID tag readability is strongly dependent on the factors that are experimented with. The level of the factors for optimum RFID system performance should be adjusted based on the particular application.

From off-label prescribing towards a new FDA.

Once a drug has been FDA-permitted for some use it can be prescribed for any use. New uses for old drugs are often discovered so a significant fraction of all prescriptions are for uses which were not tested in the FDA permitting process. The prevalence of 'off-label' prescribing has generated concern that prescribing is not scientifically sound or in the patient interest. A better understanding and appreciation of the off-label system suggests that additional FDA regulation is not warranted but that reform of the FDA towards a Consumer Reports model may substantially benefit patients.

Repackaged pharmaceuticals in the California workers' compensation system: from distribution and pricing options to physician and retail dispensing.

OBJECTIVE: The California Workers' Compensation (WC) pharmaceutical pricing system cannot price 60% of National Drug Codes (NDCs) (mostly repackaged pharmaceuticals). This study will estimate the lost savings due to repackaged pharmaceuticals and potential cost savings associated with alternative pharmacy fee schedules for repackaged pharmaceuticals. In addition, we will determine what characteristics explain repackaged costs to identify reasons for repackaged pharmaceutical use. METHODS: All pain-related repackaged pharmaceuticals were identified by NDC using claims data from the California Workers' Compensation Institute (CWCI) database during 2002. RESULTS: Repackaged pharmaceuticals represented 55% of all NDCs and 92% of all Medi-Cal non-equivalent NDCs, but only 22% ($8,494,297/$38,968,233) of total pharmacy costs. Total repackaged pharmaceutical costs could be reduced by 36% ($3,059,177) using an alternative formula based on Medi-Cal. Compared with Medi-Cal priced manufacturer-packaged pharmaceuticals, repackaged pharmaceuticals are approximately 85% more expensive on a cost-per-pill basis. CONCLUSION: We propose limiting the generous pricing of repackaged pharmaceuticals. However, Medi-Cal payment rates may be extreme, and more moderate repricing might compensate physician-dispensing time more fairly and preserve patient access.

Obstruction of critical information on over-the-counter medication packages by external tags.

BACKGROUND: Over-the-counter (OTC) medication packages are important sources of information for consumers during product selection and use. Consumers may not be able to access information from OTC packages if external tags, namely price or anti-theft tags, are improperly placed. OBJECTIVE: To determine the amount and type of information concealed by anti-theft tags and price tags affixed on OTC drug packages. METHODS: A field study was performed by evaluating packages containing acetaminophen and combinations of acetaminophen in stores located in Houston. Five packages for 4 products selected from each store after an initial survey for presence of an external tag were examined. A data collection sheet was prepared that extracted the type and amount of information concealed by these tags. Data were analyzed by performing descriptive analyses to provide an understanding of the information obscured. RESULTS: A total of 24 stores were considered in the study, and 67 products and 285 packages were evaluated. External tags, both anti-theft and price tags, obscured significant amounts of information on the principal display panel (53.4%) and the Drug Facts panel (47.7%) of OTC packages. These tags concealed crucial information on various aspects of labels such as brand names (42.3%), product description (36.3%), warnings (51.5%), uses (10.4%), and purposes (7.2%). CONCLUSIONS: Results suggest that improper use of external tags clearly obscured important information on OTC medication packages necessary for consumers to make informed decisions regarding product selection and use. Tagging practices should be altered to allow consumers full access to drug information on the product.

Labeling requirements for systemic antibacterial drug products intended for human use. Final rule.

The Food and Drug Administration (FDA) is amending its regulations to require that the labeling for all systemic antibacterial drug products (i.e., antibiotics and their synthetic counterparts) intended for human use include certain statements about using antibiotics in a way that will reduce the development of drug-resistant bacterial strains. The final rule reflects a growing concern in FDA and the medical community that unnecessary use of systemic antibacterials has contributed to a dramatic increase in recent years in the prevalence of drug-resistant bacterial infections. The final rule is intended to encourage physicians to prescribe systemic antibacterial drugs only when clinically necessary. The final rule is also intended to encourage physicians to counsel their patients about the proper use of such drugs and the importance of taking them exactly as directed.

Over-the-counter human drugs; labeling requirements. Food and Drug Administration, HHS. Final rule.

The Food and Drug Administration (FDA) is issuing a final rule establishing a standardized format and standardized content requirements for the labeling of over-the-counter (OTC) drug products. This final rule is intended to assist consumers in reading and understanding OTC drug product labeling so that consumers may use these products safely and effectively. This final rule will require all OTC drug products to carry the new, easy-to-read format and the revised content requirements within prescribed implementation periods.

Sunscreen drug products for over-the-counter human use; final monograph. Food and Drug Administration, HHS. Final rule.

The Food and Drug Administration (FDA) is issuing a final rule in the form of a final monograph establishing conditions under which over-the-counter (OTC) sunscreen drug products are generally recognized as safe and effective and not misbranded as part of FDA's ongoing review of OTC drug products. FDA is issuing this final rule after considering public comments on the agency's proposed regulation, which was issued in the form of a tentative final monograph, and new data and information on sunscreen drug products that have come to the agency's attention. FDA is also issuing final rules regarding the labeling of certain cosmetic products to inform consumers that these products do not provide protection from the sun.