Hello, everyone. My name is Gretchen Sasha. I'm a critical care pharmacist at the Cleveland Clinic, where I practice in the medical ICU. Today I'm going to continue the discussion on medication shortage mitigation and prevention by discussing the specific aspects of mitigating medication shortages. You may not realize that there are actually guidelines that pertain to this question, and I'm going to give credit where credit is due and state that the discussion we will be having today follows the recommendations of the American Society of Health Systems Pharmacists, or ASHP's, 2018 guidelines on managing drug product shortages, which are published in their corresponding journal in AJHP. Now the goal of this talk is that by the end you will be able to list factors leading to medication shortages in hospital systems, discuss the impact of medication shortages at the patient level, and then finally discuss methods to mitigate medication shortages. I'm sure most, if not all, of us listening in today have been impacted in some capacity by drug shortages and are not surprised to hear that this is an unfortunately large issue. You can see the rate of active drug shortages by quarter starting at quarter four of 2015. It is disheartening to see that this number has increased over the years, albeit with some variation, but in the last quarter of 2021 there were 246 active drug shortages. Additionally, you can see the number of new drug shortages presented here annually beginning in 2001. This number has also varied, but exceeds 100, with 114 new drug shortages reported in 2021 alone. What is noted with the different colors on this graph is the percent of new drug shortages that are injectable drugs, and overall through the years, on average, 55.6% of new drug shortages are of injectable products, with 66% of the new drug shortages in 2021 being injectable drugs. So this issue does not just impact outpatient prescriptions, but heavily impacts our inpatient injectable agents. I won't belabor the discussion on what precipitates drug shortages as Dr. Lee focused on this piece in the prior session, but as a refresher, and as I'm sure you recall, medication shortages can occur for many reasons, the most common factor being manufacturing and quality problems or a failure of quality management at the final product's manufacturing site. Additionally, production delays and overall lack of capacity can occur particularly when there is a single manufacturer of a drug product and others don't have the capacity to make up for this difference. The fact that the market for drug products is unique and does not follow the typical principle of supply and demand can impact supply if any of the above occurs. Additionally, there can be shortages of active pharmaceutical ingredients or raw materials, there may be restricted distribution and allocation of drug products, and finally, poor ordering practices like stockpiling and hoarding can result in and worsen drug shortages. Drug shortages in themselves have far-reaching consequences, including the impact on patient care, the strain on healthcare providers and institutions, and they can result in significant financial implications. And I want to briefly touch on each of these pieces. The collateral damages that drug shortages create includes excessive frustration with providers in which they perceive a significant impact on patient care, frustration regarding the lack of communication and information on current and upcoming drug shortages, as well as the cause and duration of shortages. Additionally, there are significant resources that are utilized to mitigate and plan for shortages. Lastly, shortages increase the cost of delivering patient care, largely through the personnel costs required to manage multiple pharmacy automation systems and electronic medical record or EMR changes that must be adjusted in the face of these drug shortages. In fact, it is estimated that the annual labor cost for all U.S. health systems to manage drug shortages is $216 million, a statistic that was reported in 2011, so you can imagine how this number has done nothing but increase over time. From the patient perspective, drug shortages result in increased out-of-pocket costs, increased adverse drug events, increased drug errors, and increased frustration and complaints by patients. Lastly, although I would argue that the above are all examples of patient outcomes, some data may indicate that clinical outcomes like mortality may be impacted as well. However, other than survey data, there are few trials that evaluated the impact of drug shortages on patient-specific clinical outcomes, at least in the realm of critical care medicine. But the one study I do want to briefly address evaluated the 2011 shortage of norepinephrine because of production interruptions at three different drug manufacturers, which then persisted for one year. This evaluation utilized the Premier Healthcare Database to assess hospital and patient-level utilization of vasopressors in patients with septic shock at hospitals which were impacted by the shortage, and then compared their use in quarters impacted by the shortage to quarters not impacted by the shortage. And you can see this data here on the slide for you. Not surprisingly, norepinephrine utilization decreased during the shortage quarters by about 30% compared to non-shortage quarters. And in that time, and what is assumed in response to the shortage, phenylephrine use increased by over 18%, as well as dopamine and vasopressin use, but to a lesser degree. What this study also showed utilizing a patient-level mixed effects logistic regression analysis is that being admitted to a hospital impacted by the norepinephrine shortage during the norepinephrine shortage quarters was associated with a 15% increased odds of death compared to being admitted during quarters outside of the norepinephrine shortage. Now this study is not able to determine causality between the shortage and mortality, but it does leave one to conclude and wonder whether the shortage and utilization of alternative agents could be culpable. Now responding to and mitigating drug shortages is an extremely important and timely process that needs a thoughtful and strategic plan to execute successfully. However, for that to occur, institutions should establish a well-defined management strategy to address patient shortages when they occur. Ideally, this should be in place before drug shortages occur in patient care and risk patient care. These pieces consist of identifying a drug shortage team to help monitor drug shortages, as well as plan and develop response activities. Depending on the size of the institution and the facility, as well as the degree and number of pertinent drug shortages that are current and expected, this may need to be a pretty robust team. Secondly, to develop a resource allocation committee to directly oversee the allocation of scarce resources or those drugs that are in short supply, and this should include representation from the various service areas that are implicated by the drug shortage. Third, a formalized process for approving alternative therapies should be established. Now whether this includes C-suite approval or P&T formulary committee development and buy-in, it may vary depending on the drug shortage and the institution. And then lastly, a process for addressing ethical considerations needs to be interwoven in this process to ensure the needs of individual patients are being balanced with the needs of the institution as a whole. Now when a shortage is identified, the drug product shortage team should conduct an operational and a therapeutic assessment to evaluate the downstream implications of the shortage. Operationally, what this can and should be done by designated members of the pharmacy department include validating the shortage details as well as the timing and duration of either directly through the product manufacturer and distributors or using the ASHP or FDA databases that are detailed on the slide. An evaluation of the current supply on hand and inventory should be conducted including all stock both in the pharmacy as well as that on the floor and in automating dispensing cabinets and this should be used to determine the duration of supply on hand. A true use history should also be conducted to determine how much supplies actually used and how much will actually be needed to get through the shortage timeframe. And then finally, availability of the implicated drug and alternative agents should be assessed through the institution's distributor to see how long they will be able to supply the shortage drug and if alternatives are available and in stock. These pieces are necessary to determine how the institution will get through this first phase of the shortage in which you start to use up your own supply and then begin the development of a plan to mitigate it. At the same time as the aforementioned analysis is conducted, dedicated members of the drug shortage team should be assessing the primary patient populations affected and identifying therapeutic alternatives and overall developing a plan to mitigate the shortage. Prioritization by the resource allocation committee should be done to identify patients who should be triaged to receive the drug in question and which populations may be suitable to receive alternative agents. For example, during a shortage of an IV medication, is there an oral alternative available and can the IV formulation that is short be conserved for patients who are unable to take oral medications? The second part of this step is then to actually identify therapeutic alternatives that have ample availability and can maintain availability with increased demand. This may require key stakeholder input as well as approval by P&T formulary and their evaluation and approval to logistically implement this. All of these factors should be done in conjunction to determine a definitive plan for the shortage, now be that subbing to alternatives like we've discussed, adding a restriction criteria and getting the necessary approval, utilizing the EMR and clinical decision support to create alerts about the drug shortage or recommending alternatives, conserving drug by limiting or adjusting PAR quantities, centralizing inventory. You can either also encourage or enforce IV to PO conversions of medications. And then finally, if it's feasible and realistic at your institution, compounding the affected drug. Also realize that a combination of these efforts and strategies will likely be necessary. To actually implement the plan, it is extremely important not to forget the communication and transparency aspect of implementation. Clear communication with all affected parties, physicians, providers, nurses, pharmacists, pharmacy technicians, et cetera, should be established to convey the status of the shortage, its duration, the proposed and soon to be implemented plan, and then any action items for them. Multiple communication methods are always better than one. Don't just send an email that may go unread and be lost in an inbox of hundreds of emails, but rather send an email, add an alert in the EMR, send out institution bulletins, discuss the change and shortage at service area huddles and meetings, and ensure this communication goes out in a timely manner in relation to when your institution becomes affected by the shortage. Encourage providers and specialty areas to assist in communication dissemination. For example, if you have critical care pharmacists, have them assist in communication to their teams or the nursing leadership in their areas. And lastly, which we have been hedging at now, is implement the plan. Set your go-live date and make the changes we have discussed throughout this talk. To provide some real-world examples of mitigation strategies that have occurred in the past, I'll start with the recent metronidazole shortage at the end of 2021. Options for mitigation of this shortage could include implementing a drug shortage alert in the EMR, alerting providers to the shortage, and then directing them to alternative anaerobic covering agents, and conserving use for patients with severe anaerobic infections that may not be suitable for alternative agents like severe fulminant C. diff or patients who can't receive oral alternatives. Additionally, removing IV metronidazole from pertinent order sets can and should be considered. A second example is the IV post-econazole shortage that occurred earlier this year. Strategies can be developed for this agent in that post-econazole tablets can be considered for patients who tolerate oral administration or the suspension if patients have feeding tubes. An IV isavuconazole or voriconazole can be IV alternatives for patients unable to take oral agents depending on the indication for post-econazole. Epinephrine 1mg and 10mL syringes have been intermittently on shortage for some time now, and these are the syringes typically stocked in code boxes or code carts. Consideration for mitigation of these shortages include creating kits of epinephrine 1mg vials with appropriate diluent, and even including syringes, needles, and a card with instructions, and then putting these kits as a substitute in code boxes and code carts, so that during a code or emergent situation, the provider preparing medications has all the necessary supplies to compound epinephrine syringes on site. Additionally, if epinephrine syringes are included as floor stock in automated dispensing cabinets, consider pulling these back to conserve supply only for code boxes and carts, and if you include, say, six epinephrine syringes in code boxes, consider limiting this to three or four syringes. And then finally, the recent IV heparin shortage. A few solutions could be to encourage the transition of heparin to low molecular weight heparins or the direct oral anticoagulant agents when available and able, and if this is something that is feasible at your institution, consider compounding heparin infusions from heparin vials. Now, I utilized non-COVID examples, as I'm sure we're all very much burnt out from COVID, but I do acknowledge that drug shortages were a very real and big scare at the beginning of the pandemic, specifically in regards to sedative agents, and alternative agents were heavily utilized as a result, but I wanted to provide some real-life examples of how these shortages can be mitigated. The last piece I want to address are some other mitigation and planning strategies that can be successful and may be attractive for your institution. This includes developing a core committee with regularly scheduled meetings to discuss active shortages, their status, the status of any mitigation plans that have been rolled out, and any other outstanding items that may be needed. This team should include key stakeholders from various service areas and departments. You can also schedule monthly or even quarterly meetings for physicians and frontline providers for enhanced transparency and communication of active shortages and any changes that may impact their standard workflow. And then a final consideration would be to develop an internal database with active shortages, including detailed drug supply and mitigation strategies for each impacted drug. To conclude, drug shortages have a direct impact on providers as well as patient care and patient outcomes. In order to successfully plan for drug shortages, a drug shortage team with key stakeholders should be created to address future shortages, and when they are identified, both an operational and therapeutic assessment are key to developing an appropriate plan to mitigate the shortage. And finally, communication is absolutely vital to ensure all parties affected are aware of the shortage and the plan for mitigation. Thank you to everyone joining in and listening to this talk today, and thank you to SCCM for inviting me to present on this very prevalent topic. Have a great day, everyone.

medication shortages

active drug shortages

manufacturing problems

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mitigation strategies