Child-Resistant Packaging for E-Liquid: A Review of US State Legislation

This article delved into the issue of a lack of child-resistant packaging for liquid nicotine used in electronic cigarettes, otherwise known as e-liquid.  The use of e-liquid has increased dramatically over the past five years, and along with this increase, there has been a rise in poisonings of children from ingesting or having skin exposure of e-liquid.  There has been no legislation at the federal level passed to enforce the use of child-resistant packaging on e-liquid.  Many states over the past three years have taken the initiative to create their own legislation regarding child-resistant packaging of e-liquid, but there is much variance between the policies of different states, and many of the state laws on this subject are not being enforced.  A review was conducted on the laws in each state that have been proposed and/or passed concerning child-resistant packaging of e-liquid.  The authors set four benchmarks to determine if the legislation of each state is effective.  They include having broad definitions that will allow for flexibility as e-cigarette technology and trends advance and change, packaging standards based on the Consumer Product Safety Commission guidelines, clearly defined penalties for violation of the law, and a clear grant to a certain authority to enforce the law.  Only three states were determined by this review to meet these four benchmarks for efficacy.  The FDA has voiced their concern on this topic, but federal legislation will not likely be put into effect until 2017 or later.  As states recognize the e-liquid child-resistant packaging situation as an issue and begin to implement their own legislation during the wait for federal legislation on the subject, the states should base their laws on the successful legislation of those three states, Indiana, Minnesota, and Washington.

I believe this problem arose because of the marketing that goes into e-cigarettes and e-liquid.  Instead of e-liquid manufacturers treating e-liquid like the drug that it is, they treat it as a trendy, popular product.  E-liquid did not have child-resistant packaging from the beginning of its production because child-resistant packaging does not fit into the fun, attractive image of e-liquid and use of e-cigarettes.  Do you think there should be more regulation put into place on how e-liquid is advertised in addition to how it is packaged?

Frey LT, Tilburg WC. Child-Resistant Packaging for E-Liquid: A Review of US State Legislation. Am J Public Health. 2016;106(2):266-8.

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Sharing Clinical Trial Data: A Proposal From the International Committee of Medical Journal Editors

Have you ever wondered what happens to individual-patient data (IPD) from a clinical study after the results of that study are published?  It turns out that much of the IPD is stored privately and not shared with other researchers or individuals that could benefit from the data.  This lack of data sharing is why the International Committee of Medical Journal Editors wrote this article.  This committee includes representatives from many of the big names in medical journals including JAMA, Annals of Internal Medicine, New England Journal of Medicine, and the British Medical Journal.  The committee proposes a new set of requirements for researchers who wish to publish their findings in any of the member journals of the committee.  These requirements are still a work in progress, and the ICMJE is actually accepting feedback on them through April 18, 2016.  The requirements include agreeing to sharing all of the IPD garnered from a study at the time of application submission for the study, and agreeing to giving credit where credit is due when the IPD from a past study is used in a review or a future study.  The new requirements would require researchers to make available IPD from a study no later than 6 months after the publication of study results.  The committee purports that this data sharing will lead to increased collaboration, increased transparency of trial results, and as a result increased trust and confidence in results of clinical trials.  Data sharing on a broad scale will also help researchers and the medical community in general to maximize the usefulness of data from patients, helping to ensure participants in studies that their information has the potential to make a difference beyond the results of just one study.

I am a big supporter of this data sharing movement and the newly proposed requirements for data sharing from the ICMJE.  I had not given data sharing much thought in the past, but it seems like the ethical choice in terms of what should be done with de-identified IPD after the conclusion of a study.  Research, after all, should not be done for the sake of money or credit, but for the sake of the advancement of medicine and the health of patients, and data sharing has the potential to help immensely in these efforts.

Taichman DB, Backus J, Baethge C, et al. Sharing Clinical Trial Data: A Proposal From the International Committee of Medical Journal Editors. JAMA. 2016;315(5):467-8.

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Drug Discontinuation and Follow-up Rates in Oral Antithrombotic Trials

A common issue concerning the validity of trial results is the rate of follow-up and the completeness of follow-up within the study.  If follow-up is incomplete, there is missing data that cannot contribute to the results of the study.  This research letter examines the difference between the reported values of follow-up rates in trials in published material versus the FDA-calculated follow-up rates for a variety of oral antithrombotic drugs.  23 of 25 trials were discussed; two were excluded because they did not include follow-up information.  270,089 patients were randomized and the trials ranged in duration from 8-43 months.  The mean for individuals who were “lost” to follow-up was 0.4% in published material, whereas the FDA-calculated rates for incomplete follow-up had a mean of 12%.  This difference is quite large, and could have consequences impacting the validity of trial results.  The difference in end point rate was examined for the trials, and the mean end point rate difference was 1.3%.  The FDA-calculated incompleteness of follow-up rates were much larger than the end point rate difference.  This all suggests that the differences in end point rate may be due to differences in follow-up rather than differences in the actual effects of the antithrombotic drugs in the trials.  The mean drug discontinuation rate in the trails was 24.9%, which explains why there would be high rates of incompleteness of follow-up.  Some loss of follow-up is inevitable, but implementing a standard of follow-up assessment and reporting would increase the validity of drug trial results.

It could be argued that the results of trials could be interpreted the same despite inconsistencies in reported follow-up rates.  How important do you think standardizing assessment and reporting of follow-up rates is to the validity of drug trials?

Marciniak TA, Cherepanov V, Golukhova E, et al. Drug Discontinuation and Follow-up Rates in Oral Antithrombotic Trials. JAMA Intern Med. 2016; 176(2):257-9.

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U.S. Poison Control Center Calls for Infants 0-6 Months Old

This article concerned a retrospective study on poison control center calls about infants aged 0 to 6 months.  The study used data from the National Poison Data System that combines all the electronic records of all the United States Poison Control Centers.  The study was conducted to explore the reason behind the majority of poison center calls made for infants in the first six months of their lives.  Infants at that stage of development have very little mobility, reducing the possibility of poisoning by exploration, a common cause for poisoning of infants and toddlers older than six months of age.  This rationale would indicate that poisoning caused by a mistake of a caregiver is more common in younger infants than it is in infants and toddlers older than six months of age.  Many programs for young parents that address the issue of poisoning focus on the need to keep dangerous substances out of reach of children, but the instances of caregiver mistakes in poisoning events of infants 0-6 months old would not be prevented by keeping medicines inaccessible to the infants.  Also, most of these programs do not begin poison education before children reach six months of age anyways.  The results of the study presented a couple key takeaways.  One of the results was that 97.5% of poisoning events for this age group originated in people’s homes, whereas only 85.2% of the phone calls made about these events originated in people’s homes, with others originating from health care facilities, meaning some caregivers travelled to a health care facility before contacting a Poison Control Center.  Additionally, the percentage of calls made for unintentional poisonings by the caregiver for this early infant age range was a large proportion of the total poisonings for this age range, of which there were numerous recorded over the 10-year (2004-2013) period of the study.

I believe that early education of parents about the resource of Poison Control Centers and about how to properly use medications in infants would prevent many of the poisoning events that occur in the age group of infants 0-6 months old.  The study also concluded that increased education concerning PCC’s and proper infant medical care to parents before they leave the nursery at the hospital would eradicate many of the poisoning occurrences in this age group.  What do you think the best approach to reducing poisoning of infants aged 0-6 months in the United States is?

Kang AM, Brooks DE. US Poison Control Center Calls for Infants 6 Months of Age and Younger. Pediatrics. 2016;137:1-7.

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Overtreatment of Osteoporosis in a Health System

This article concerns a study that addresses the overtreatment of osteoporosis in a health system.  The study was conducted at UC Davis health system from 2006 to 2011.  It analyzed electronic health records to assess the rate of initial DXA screening for osteoporosis and the rate of new prescriptions prescribed based on the T scores reported from these initial DXA screenings.  Women aged 40-85 were included in the study, and it was determined if they had any or all of six risk factors associated with osteoporosis.  The study purported that there is overtreatment of osteoporosis largely in part because T scores indicating osteopenia or osteoporosis from non-diagnostic anatomical sites were used to determine the need for osteoporosis treatment.  Some areas of bone are suggested for diagnosis of osteoporosis by the International Society for Clinical Densitometry guidelines, while other anatomical bone areas are not.  The study determined that appropriately, most women of the 6150 women in the study with main-site osteoporosis according to their screening and T scores received new treatment for osteoporosis.  However, less appropriately, 47.7% of the women with non—main-site osteoporosis also received new drug treatment.  That means that 47.7% of the women in the study were potentially prescribed osteoporosis treatment not in accordance with the International Society for Clinical Densitometry guidelines.  The study also suggested that furthermore, some of these prescriptions were inappropriate because some of the younger women in the study were recommended to undergo the DXA screening not in accordance with the international guidelines about who should be screened.  These findings are not necessarily generalizable to health systems beyond UC Davis, and more research needs to be done.

I believe that there are a variety of ways to combat this issue of overtreatment within a health system, one of them being that radiologists who report the T scores should only report the scores from the main sites for osteoporosis diagnosis as provided by the international guidelines.  This suggestion amongst others was provided by the article.  What do you think are other ways overtreatment of osteoporosis could be combatted in health systems?

Fenton JJ, Robbins JA, Amarnath AD, Franks P. Osteoporosis Overtreatment in a Regional Health Care System. JAMA Intern Med. doi:10.1001/jamainternmed.2015.6020 (published 4 January 2016).

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FDA’s Role in Regulating Generic Drug Affordability

This article from The Journal of the American Medical Association makes some suggestions to the FDA on how to manage the affordability of off-patent pharmaceuticals.  Historically and currently the FDA stays away from making decisions based on the economics surrounding drugs and drug-pricing.  However, this has led to exacerbated issues when it comes to drug cost for generics in non-competitive markets.  The article details how in a competitive market if one generic manufacturer dramatically increases the price of their product, another manufacturer can sell the product at a much lower cost and do well in the market.  However, in a non-competitive market, if the sole manufacturer of a generic drug decides to increase the price, people have to pay the price set by the manufacturer in order to get the medication.  Additionally, when there have only been one or two manufacturers of a drug historically, a drug shortage can easily occur.  If those one or two manufacturers fail temporarily or increase their prices drastically, the United States is unable to obtain their specific drug product and get it to patients affordably except by importation from other countries.  The article asserts that it would do the drug industry good in the U.S. if the FDA began involving itself in issues of drug-pricing regulation and management.  Suggestions from the article include changing the FDA’s generic drug application review process by prioritizing drugs that would fall into a non-competitive market if approved, temporarily permitting compounding of drugs that are facing shortage issues due to manufacturer failure or dramatic price increase, and permitting importation of drugs from reputable sources in the instance of a shortage.

I believe I am of the same opinion as the article: that it is the FDA’s duty to protect the public, and the service of regulating drug-costs falls under that category.  If a life-saving drug’s price skyrockets for the benefit of the manufacturer and a patient is no longer able to purchase the ridiculously high-cost medication, the FDA has failed in one way.  If the FDA were to change their ways it could have an incredible impact on the drug market in the United States, for better or for worse.  Do you think the FDA should play a role in drug price regulation?  Or do you tend to think that drug companies are companies like any other and should be able to price drugs how they please?

Greene JA, Anderson G, Sharfstein JM. Role of the FDA in Affordability of Off-Patent Pharmaceuticals. JAMA. 2016;315:461-462.

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Examining Acuity Adjustment Metrics and Which Is Best for Monitoring Long-term Medication Expense

This article examined and compared two acuity adjustment metrics for monitoring medication expense over time in a health system.  The health system used for the study was the Ohio State University Wexner Medical Center.  The two metrics evaluated were case-mix index (CIS) and pharmacy intensity score (PIS) based on the markers relative weight (RW) and pharmacy intensity weight (PIW) respectively.  These acuity adjustment metrics are used to estimate the cost of medications for different diagnosis-related groups within a health system.  CIS and PIS provide guidelines for budgeting for medication within a health system, based on what diagnosis-related groups are present in the health system and how large those groups are.  It has long been debated which metric is better for predicting accurate medication expenses over time, and the differences between and accuracy of the two metrics have not been well-studied.  Determining which metric is more accurate is important because a large portion of a health system’s budget often goes towards medication, and even a small percentile difference in cost of medication expenses over time can mean a large difference in dollars for a health system.  The study was only conducted at one center, but the researchers attempted to make the results more generalizable by focusing on the data of medication expenses over time for only the top ten diagnosis-related groups nationally.  This way, the results were not skewed towards the diagnosis-related groups that the Wexner Medical Center sees more of than other health systems, such as cancer patients.  The results of the study indicated that the pharmacy intensity score (PIS) provided on average a more accurate estimate of medication expenses over time for all the diagnosis-related groups included in the nine-month study.  The article detailed that for some diagnosis-related groups with high variability in medication expense on an individual patient basis, neither metric was very good for estimating average medication expense over time.  However, overall, the conclusion was that PIW correlated more strongly with true medication expense than did RW, meaning that PIS is overall a better acuity adjustment metric, keeping in mind that there is still much research to be done in this area.

This article is not an article I would normally read based purely on the dryness of the title, but after reading it I have a greater understanding of and appreciation for the business aspect of managing medications in a health system.  Personally as a student pharmacist I find it easy to get wrapped up in the patient care aspect of pharmacy, and to forget that everything has a price.  With medications in particular, that price can be quite large, and can quickly multiply when the total medication expenditure of a health system is analyzed as a whole.  I am glad I read this article because I learned something new about how health systems can better budget for medications, which is a topic I had never considered before.

Brink HL, Naseman RW, Porter K, et al. An evaluation of acuity adjustment metrics to track medication expense over time. Am J Health-Syst Pharm. 2015;72:2157-65.

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Use of Stimulants in Children of Mentally Ill, Increased Risk of Psychotic Symptoms

This article concerned a study showing that children aged 6-21 with one or more parents with a severe mental illness had a higher likelihood of experiencing psychotic symptoms when taking stimulants.  It was once thought that psychotic symptoms, including hallucinations, delusions, and psychotic-like experiences, were rare side effects of stimulants in children.  This study demonstrated that it might not be the case that they are such rare side effects, especially in children of one or more parent with a severe mental illness.  In the study, the children of parents with mental illnesses including major depressive disorder, bipolar disorder, and schizophrenia were tested for ADHD, a common indication for use of stimulants in children.  Of the children with ADHD, those that had taken stimulants had a much higher rate of experiencing psychotic symptoms than those who had not taken stimulants.  The study showed that there was a temporal relationship between taking stimulants and experiencing psychotic symptoms.  It also ruled out the possibility that the real cause of the psychotic symptoms was ADHD and not the use of stimulants.  The study used multiple sophisticated instruments for assessing psychotic symptoms, and the results were statistically significant.  Additional studies are necessary to confirm that there is indeed a causal relationship between stimulants and psychotic symptoms in children of parents with mental illnesses.  Further studies will also be necessary to determine of the stimulant methylphenidate, the most frequently seen in the study, produces results that can be generalized to other stimulants.  However, the results of this study alone are enough to encourage doctors and psychiatrists to consider familial history of severe mental illnesses when considering prescribing stimulants for children with ADHD.

I was happy to see this article because I think it is important to continue testing in the field of mental illnesses and medications for learning disabilities and mental illnesses.  There has always been a stigma attached to mental illness, and it is possible that this stigma has affected how mental illness and medications for mental problems have been studied and presented to the public.  Further studies in this area will help to clear any misconceptions that have formed and to improve medical practice in this area.

MacKenzie LE, Abidi S, Fisher HL, et al. Stimulant Medication and Psychotic Symptoms in Offspring of Parents With Mental Illness. Pediatrics. 2016;137:1-10.

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