Special Issue: Drug shortages: National Survey Reveals High Level of Frustration, Low Level of Safety
An exhaustive account of frustrations, difficulties, and patient safety concerns came across loud and clear from more than 1,800 healthcare practitioners (68% pharmacists) who participated in our July-September 2010 survey on drug shortages.1 Many respondents stated that the conditions associated with drug shortages during the past year have been the worst ever, without a glimmer of hope for any improvement in the near future. They feel unsupported by the Food and Drug Administration (FDA) and perplexed regarding why the US is experiencing drug shortages of epic proportion that are often associated with third-world countries. Respondents clearly believe the public is severely impacted by this issue, and several suggest that the problem has risen to the level of a national public health crisis.
By far, respondents were most alarmed by: the ever-increasing volume of critically important medications in short supply; the use of less desirable, often expensive, unfamiliar alternative drugs—if even available; the potential for errors and poor patient outcomes caused by absent or delayed treatment or preventable adverse drug events associated with alternative drugs or dosage forms; the lack of advanced warning about an impending shortage; and precious clinical hours lost to time-consuming activities required to manage drug shortages.
Frequency of drug shortage difficulties
During the past year, more than half of the respondents reported frequently or always encountering every one of the potential difficulties associated with drug shortages identified in our survey, which are listed in the next column in descending order starting with the most frequently encountered difficulty:
- Little or no information available about the duration of a drug shortage (85%)
- Lack of advanced warning from manufacturers or FDA to alert practitioners to an impending drug shortage and suggested alternatives (84%)
- Little or no information about the cause of the drug shortage (83%)
- Substantial resources spent investigating the shortage and developing a plan of action (82%)
- Difficulty obtaining a suitable alternative product (80%)
- Experience a significant financial impact (78%)
- Lack of a suitable alternative product (70%)
- Substantial resources spent preparing and/or administering the alternative products (69%)
- Risk of adverse patient outcomes (64%)
- Internal hoarding of medications associated with impending shortages (58%)
- Physician anger towards pharmacists/nurses/hospital in response to a drug shortage (55%).
Physicians and pharmacists, particularly pharmacy managers and directors, reported encountering the above-listed problems more frequently than nurses, especially in areas such as spending resources to investigate shortages, developing a plan of action, hoarding medications in short supply, obtaining a suitable alternative, and experiencing the financial impact of purchasing drugs off contract or through secondary markets, or higher rushed delivery costs. While all professional disciplines clearly reported grave concerns regarding the risk of adverse patient outcomes during drug shortages, physicians reported encountering this risk more frequently than others, preceded in frequency only by lack of information about the causes and duration of shortages and lack of advanced warning from manufacturers or FDA.
Near misses, errors, adverse outcomes
Approximately one in three (35%) respondents reported that their facility had experienced a near miss during the past year due to a drug shortage. About one in four reported actual errors and one in five reported adverse patient outcomes during the past year due to drug shortages. More staff level practitioners (21%) reported adverse patient outcomes than administrative staff or directors/managers (18%), and as many as one in three (33%) physicians reported an adverse outcome caused by drug shortages this past year, more than pharmacists (21%) or nurses (16%). However, many respondents repeatedly commented that errors and adverse patient outcomes were not shared with them on a routine basis, were based on sporadic voluntary reporting, or were difficult to quantify. Thus, many felt the frequency of errors and adverse outcomes due to drug shortages is much greater than reported, and that not being aware of events did not mean they were not happening.
Respondents provided disquieting details regarding actual near misses, errors, and adverse patient outcomes associated with more than 50 drugs that had abruptly become unavailable, often without adequate notice. Table 1 provides just a glimpse at the many—more than 1,000!—near misses, errors, and adverse outcomes reported by respondents that occurred during the past year due to drug shortages. Especially troubling is that many of the drugs involved in the shortages are high-alert medications, such as propofol, heparin, epinephrine, morphine, neuromuscular blocking agents, chemotherapy, 50% dextrose, and parenteral electrolyte supplements; if not a high-alert medication, many other drugs in short supply are essential and lifesaving, such as antibiotics, IV fat emulsion, and fosphenytoin.
Lack of alternative medications
Some drug shortages result in situations where a viable alternative is not available. For example, according to respondents, the shortage of amikacin and acyclovir has contributed to patient deaths from infections that were only sensitive to amikacin or treatable with acyclovir. Alternative antibiotics and antiviral medications were of little help in these situations. The shortage of various chemotherapeutic agents and adjunct therapy is another prime example. One respondent reported that stem cell transplantations were on hold because etoposide is not available. Another respondent said that important investigational drug studies have been put on hold because an adequate supply of adjunct medications required in the protocol could not be assured. Some hospitals and outpatient surgical centers have been forced to postpone surgeries indefinitely due to shortages of propofol and neuromuscular blocking agents; some have transferred patients to facilities that still have a supply of these crucial medications.
Issues with alternative medications
In other cases, alternative drugs or dosage forms/strengths are available when a drug shortage occurs, although the purchase price is often high. But even when alternatives can be identified, three serious problems were repeatedly voiced by survey respondents.
First, an alternative medication is often just that: an alternative to a drug with superior efficacy and/or a lower risk profile. For example, according to our survey respondents, alternative agents used in place of propofol for deep sedation have resulted in higher incidences of agitation and self-extubation in ventilated patients, and postoperative nausea and vomiting (related to the sedative, not analgesics) in surgical patients, which often led to extended hospitalization. To cite another example, an alternative medication may pose greater risk to patients with renal impairment than the drug in short supply. Certain diseases and conditions can be compromised when alternative products produce less than optimal treatment outcomes. In some instances, patients have allergies or a history of adverse reactions to the alternative medication and are left without an effective treatment option.
The next issue survey respondents raised is that the supply of alternative products can quickly become exhausted, leading to a secondary shortage of the alternative medication. For example, supplies of HYDROmorphone, a commonly used alternative during the morphine shortage, have become increasingly more difficult to obtain, particularly lower dose unit-of-use HYDROmorphone syringes. Thus, HYDROmorphone injection now joins morphine injection on the drug shortage list. The demand for an alternative drug may outpace the current supply, and companies that manufacture the product may not be prepared to address the sudden increased demand. The practice of hoarding drugs and viable alternatives in short supply by facilities places further demand on manufacturers.
The third pressing issue raised by respondents is the risk of an error or adverse outcome when being asked to use unfamiliar alternative drugs. What is the correct dosage range and dosing frequency of the alternative drug? How is it prepared, stored, and administered? Are there untoward side effects that require patient monitoring? With so many drugs in short supply, several respondents admitted to increasing difficulty in just remembering which products are involved and what the suitable alternatives are—let alone how to safely prescribe, prepare, dispense, and administer the alternative drugs.
Physicians are asked to prescribe unfamiliar alternative drugs on the spot when called about an order for a drug in short supply; pharmacists are asked to safely dispense alternative medications, which often require additional unplanned time to prepare; nurses report that they never know what to expect when gathering medications. Will it be hydromorphone 1 mg/mL syringes in the automated dispensing cabinet? 2 mg/mL syringes? A 10 mg/mL vial? Will a totally different drug be required as an alternative? One nurse respondent stated, “I have lost count of how many times I have caught or witnessed another nurse catch a dosing error associated with hydromorphone since we never know what to expect.”
Respondents also touched upon the ethical dilemma they face when trying to prioritize use of any remaining stock of drugs involved in a shortage. Who gets the desirable medication, and who gets what may be a less desirable alternative drug? The stress of making such decisions can be seen in the brutally honest and emotional responses from the survey participants. As noted by one respondent, when a suitable alternative for a lifesaving drug is no longer available, “I guess patients just have to die.” Another respondent asked, “What do I tell our breast and lymphoma patients? You had a curable disease but not anymore because there is no drug available?”
Lack of notification about shortages
Respondents expressed significant concern regarding the lack of prior notification regarding an impending drug shortage. Most pharmacists (40%) and pharmacy technicians (51%) learn about a drug shortage the hard way—when the pharmacy department fails to receive an ordered product from a wholesaler or manufacturer. The next most frequently cited sources (24-32%) for learning about shortages included internal purchasing staff, word of mouth from other hospitals or professional listserves, secondary market contacts, and the American Society of Health-System Pharmacists (ASHP) website. Some respondents told us they often feel the impact of the shortage before it is officially communicated as a shortage.
Very few (6-15%) pharmacists, pharmacy technicians, nurses, and physicians rely on the FDA website or an advanced notice from a wholesaler, distributor, buying group, or drug manufacturer to learn about drug shortages. Among these entities, practitioners found the buying groups and wholesaler/distributors more helpful than FDA and the manufacturer. Some respondents suggested that drug manufacturers and distributors intentionally withhold information about an impending shortage until the last moment to prevent hoarding. This delay poses a significant threat to safety because practitioners have little time to prepare for the shortage.
Half of the physicians (50%) reported learning about drug shortages from pharmacists who call them after they have prescribed a drug in short supply, or from colleagues and the literature. Likewise, most nurses (52%) told us they learn about drug shortages primarily from the pharmacy department staff or unit manager; about 30% first learn about a drug shortage when pharmacy fails to dispense a prescribed medication.
Respondents also expressed their frustrations with drug companies that fail to disclose the cause of the shortage and underestimate how long the shortage will last. The disparity between information provided by drug companies and actual resolution of the shortage was called “unacceptable” by many.
Problems with secondary markets
Respondents voiced a growing concern that secondary markets (often called gray or black markets) seem to be able to gain access to drugs that are no longer available to healthcare providers through usual sources. These secondary markets contact pharmacists to advertise availability of scarce drugs, often at exorbitant prices. Some pharmacists expressed worry about the quality of products from secondary sources and felt that the exorbitant prices breach ethical lines, particularly when the drug in short supply is an essential lifesaving medication. Further conflict between healthcare providers and drug companies arises from what appears to be allowing select groups of individuals to still have access the drug or to be given a preferential warning about impending shortages so they can stockpile the drugs.
The impact of drug shortages has taken an enormous toll on healthcare providers who are responsible for dealing with the problem, and the patients who are on the receiving end of the shortage. The man-hours alone spent on planning for the shortage, educating staff, restocking and coding the alternative products, dealing with secondary market vendors, and fielding calls from healthcare practitioners consumes a large portion of the pharmacists’ time, stealing valuable resources from clinical activities. Some respondents believe a full-time position will be needed in the future to manage drug shortages if the situation does not improve. Overall, survey respondents conveyed a real sense of crisis and are clearly looking for external support to reduce the burden and harm associated with drug shortages.
As mentioned in our article Drug shortages threaten patient safety, in our July 29, 2010 issue, ISMP and ASHP are interested in co-convening a public meeting with FDA and other key stakeholders representing the pharmaceutical industry, healthcare practitioners, regulatory authorities, and medication safety experts to explore and articulate the scope of this problem, and to develop a plan to reduce the occurrence of drug shortages and better manage them when they occur. More effective FDA oversight, a comprehensive early warning system, and patient safety and outcomes placed ahead of anyone’s profit margins are goals we hope to begin to explore at this meeting. ISMP and ASHP will keep readers apprised of progress to this end. Meanwhile, in a subsequent newsletter, we plan to provide guidelines for managing drug shortages on a local level within healthcare organizations.
Neuromuscular Blocking Agents
- ISMP. ISMP survey on drug shortages. ISMP Medication Safety Alert! 2010;15(15):4.