Edited by: Sandor Kerpel-Fronius, Semmelweis University, Hungary
Reviewed by: Frits Lekkerkerker, Consultant, Netherlands; Segundo Mariz, European Medicines Agency, United Kingdom
This article was submitted to Regulatory Science, a section of the journal Frontiers in Medicine
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
The impact on patient morbidity and mortality as a result of medicine shortages is well-recognized by all key stakeholder groups including national regulatory authorities globally (
Changing treatment when a shortage occurs brings about uncertainties as the order, preparation or dispensing procedures that are needed may also change, which may lead to medication errors (
A number of surveys have been conducted and individual cases reported to help document the extent of patient harm stemming from changes in treatment as a result of drug shortages. In the USA and Canada, the Institute for Safe Medication Practices (ISMP) provides comprehensive data reports on patient harm caused by shortages (
As a consequence, medication errors caused by shortages need to be thoroughly documented, reviewed, analyzed, and reported as part of safety procedures (
Risk assessment is also seen in medicine-shortage reporting systems, not only to assess the critical need for a medicine when there are shortages but also for the institution's ability to continue to provide patient care. This is illustrated by the system in Australia where the criticality of a medicine in a possible shortage situation correlates to its impact on patient's health and accordingly registered in the Medicine's Watch List (
Currently, apart from processes involving blood transfusion, chemotherapy, aspects of surgery, medical devices as well as medicine distribution and prescription, prospective risk assessment appears uncommon in healthcare (
With medicine shortages on the rise (
Before initiation of this study, the authors received ethical approval from the Institutional Review Board (IRB) of the University of Belgrade, Faculty of Pharmacy for the verbal consent procedure (Nb. 1221/2). Verbal agreement from all interviewees was also obtained.
This interviewing process built on a previous survey on prospective risk assessment conducted within the COST Action 15105 among 34 HCPs from 26 European countries (
An interview guide was designed for the in-depth interviews. The questions were based on the results from a preceding survey on prospective risk assessment (
Interview transcripts were analyzed through framework analysis (
Interviews were carried out with 17 pharmacists and 1 pharmacologist (
Interviewees' hospital characteristics.
<500 | 7 (50%) |
500–1,000 | 0 |
1,000–1,500 | 3 (21.4%) |
1,500–2,000 | 3 (21.4%) |
>2,000 | 1 (7.1%) |
1 | 4 (28.6%) |
2 | 3 (21.4%) |
3 | 3 (21.4%) |
5 | 2 (14.3%) |
≥10 | 2 (14.3%) |
All supply | 4 (28.6%) |
Mostly supply | 8 (58.1%) |
Supply and demand | 2 (14.3%) |
Never | 0 |
Rarely | 2 (14.3%) |
Sometimes | 5 (35.7%) |
Often | 3 (21.4%) |
Very often | 4 (28.6%) |
Never | 1 (7.1%) |
Rarely | 3 (21.4%) |
Sometimes | 7 (50%) |
Often | 1 (7.1%) |
Very often | 2 (14.3%) |
When developing risk assessment strategies, a majority of interviewees do report using primary methodological data sources that consisted of: (i) consulting existing materials on the Internet, which serves as a tool for accessing scientific publications on risk stratification and therapeutic guidelines; (ii) official websites of national medicine-regulatory bodies in Europe and the USA; (iii) healthcare-professional associations; and (iv) quality and safety information in healthcare departments. However, the interviewees repeatedly underscored that although the guiding principles and data used for risk assessment need to be accurate, independent and objective, this is not always the case: “For the risk assessment, you need to have reliable information, otherwise it's guessing. So, in many fields we are guessing, because either there is no clear information, or the responsible authorities are not willing to give them. Or they have other aims.” (Hospital Pharmacist, Austria).
By and large, interviewees regard the procedure of risk assessment as time-consuming and not appropriate for all shortages. Whereas, a sufficient number of available generic alternatives do not elicit much need for risk assessment; it is typically reserved for those situations with the greatest clinical impact on patients (including anti-infectives and cancer medicines) when deciding on an alternative treatment is more complex.
Time constraints also limit risk assessment resulting in a multidisciplinary approach not always being feasible. Albeit alerts regarding possible drug-drug interactions must be done conservatively to highlight risk and not over-alert (
Based on their experience, interviewees also report financial restraints as being a further obstacle to applying risk assessment more frequently: “Increasingly getting attention with risk assessments as an incident reporting. Still underfunded—manual lifting issues get more funding. The risk assessment is considered as part of the overall change management documentation (who needs to know, who needs to be consulted).” (Hospital Pharmacist, Ireland).
Training to be able to access, analyze and use data still seems to be an issue. Interviewees from Croatia, Bosnia and Herzegovina, and Hungary emphasized a lack of HCPs possessing sufficient knowledge on risk assessment to be able to adequately perform risk assessment. An interviewee from Ireland also commented that HCPs need better training on handling data for risk assessment and risk assessment itself.
The timeliness of data availability is also a concern. Even when access to data becomes available, it is often too late, as emphasized by an interviewee from Switzerland. This is borne out by the fact that only when reaching out for medicine data on drug availability does such data become accessible. Doubts have also been conveyed on the ability to conduct risk assessment. As underscored by an interviewee from Serbia in particular, essential information on the duration of shortages, as provided by updates from wholesalers and the industry, is often unavailable.
The importance of risk assessment and its benefits for patients, helping to achieve a better state of preparedness for potential shortages, needs to be explained more fully to HCPs. As reported by interviewees from Estonia and Belgium: “I think awareness of the fact and the knowledge of the risk assessment, that's crucial to me. […] as soon as you have people that are aware of risk assessment and see the benefit of it, so that you can use your scarce resources for the best, it's just bringing people together.” (Hospital Pharmacist, Belgium). Moreover, it was also specifically noted that awareness should be extended beyond the pharmacists themselves to the health authorities in charge: “If we are the only ones who think that this is important, this is not going to lead anywhere. We can only discuss this about it among ourselves.” (Hospital Pharmacist, Austria).
Even though there may be a general understanding of the need for risk assessment in mitigating medicine shortages, “the evidence on the impact of shortage of a drug and its extent is missing, there is no data” (Hospital Pharmacist, Hungary). Data on the effectiveness of applied risk assessment procedures is therefore found to be lacking, thereby complicating the evaluation of the real impact that risk assessment has as a mitigation tool. As a result, even communicating the effective results of implementing risk assessment based on data is a challenge, as “it should be done in writing, so actual impact can be seen and prevented” (Hospital Pharmacist, Croatia).
There is a distinct opinion expressed and shared among interviewees concerning an apparent gap in responsibility for “what to do and when you are empowered to make an assessment and then take the action” (Hospital Pharmacist UK). Generally, as reported, hospital pharmacists perceive all HCPs as needing better training on handling data for risk assessment and the risk assessment itself. In Belgium, Bosnia and Herzegovina, Cyprus and Romania, no information is available in this area. Given this feedback, either the data is missing or the guiding documents on shortage mitigation plans and supporting actions are not clearly stated by the stakeholders, both of which are concerns to be addressed.
Interviewees also view a lack of a systematic approach and the option of using electronic databases in performing risk assessment to be a concern: “risk assessment is made individually, based on experience, SmPC (e.g., indications), availability of drugs, prices and outcomes (side effects). It is not documented and follow up rarely happens.” (Hospital Pharmacist, Hungary). Furthermore, the need for IT support is essential for assessment and data dissemination as noted by one interviewee from Austria: “When you have electronic prescribing, implemented in your hospital, you have much more opportunities to control. If you don't it's more difficult you know. You have to talk to everybody, to have more meetings, then you have to say, please do this and you hope that they do that, but you are not sure, you have no technical instruments to help you in the process.” (Hospital Pharmacist. Austria).
As highlighted by an interviewee from Italy, the reactive nature of a retrospective risk assessment—such as with Root Cause Analysis (RCA)—seems to be not as preventative for shortages when compared to the prospective form as Failure Mode and Effects Analysis (FMEA). It is therefore possible to better comprehend and prioritize risks in time and promptly react. In particular, prospective risk assessment is also viewed as a tool which creates faster pathways for medicine substitution before an actual shortage occurs, thereby bringing about tangible clinical benefits for patients. Although interviewees report risk assessment needing to be done in advance, in order to be pro-actively ready with possible solutions and the risks of providing a substitute to patients: “risk assessment needs to happen before an alternative goes to the wards” (Hospital Pharmacist, UK), it is still widely reported that risk assessment is carried out only when the shortage and the need do so occurs.
Interviewees asserted that the risk assessment needs “to be some kind of independent [sic]” and not tailored in the sense that “everyone conducts the assessment for him/herself while it should be the other way around” (Hospital Pharmacist, Germany). Moreover, they point out that risk assessment should be conducted in a systematic and standardized manner in order to not merely solve current problems related to shortages, but to help minimize future problems and equip HCPs as well with the necessary skills to act more efficiently the next time a shortage does occur.
A noted concern that needs to be specifically addressed is that applied risk assessment seems not always to follow scientific rigor: “My experience is that many people use the risk assessment in the way they want to use it so it's in many cases it's more politics than really, what is should [sic] be like science.” (Hospital Pharmacist, Germany). On this basis, as an interviewee from Finland commented, the risks not only need to be clearly defined, but multidisciplinary teams must take the patient's perspective into account throughout the assessment process.
Depending on the complexity of the substitution, interviewees from Belgium and Germany reported that a structured decision making process occurs concerning medicine substitution within Drug and Therapeutics Committees (DTCs). Whereas, in Italy, procedures appear to be more applied to compounding, as well as automated production and dispensing systems compared to medicine shortages. When a generic substitution occurs, pharmacists provide data quickly on an alternative into electronic prescribing systems. Similar to the situation in Estonia, if a therapeutic alternative is needed, physicians are involved into the discussion within DTCs and nurses are fully informed of the substitute's administration patterns.
In Croatia, Cyprus, Estonia, Hungary, Serbia and Switzerland, risk assessment is conducted in everyday practice on a case-by-case basis. In Belgium, Hungary, and Serbia and Belgium risk assessment takes on differing forms depending on the severity of the medicine shortage. In Serbia, for example, the healthcare system performs assessments quickly but only if an appropriate alternative exists at the immediate healthcare-facility level; if not, the Serbian Ministry of Health and National Health Insurance Fund intervene and propose measures based on their own risk assessment. Depending on the patient population size affected and the duration of the shortage, DTCs in Hungary take differing measures to cope with carrying out a quick risk assessment that provides outputs in terms of whether the needed generic substitution is feasible. Otherwise, the DTCs and national task force must be involved, including a more complex analysis and therapeutic proposals. Risk assessment is incorporated into a healthcare facility's accreditation and certification system in Bosnia and Herzegovina as part of the overall safety management plan, while health, safety and quality officers in Cyprus provide training on risk assessment applications in hospital.
An interviewee from Austria (HCP and clinical risk manager) applies a clinical incident reporting (CIR) system based on general risk assessment procedures (such as FMEA) in the overall quality management via electronic tools, but not in the area of medicine shortages. The belief was also expressed that risk assessment is currently linked more to procurement and should be performed prior to tendering procedures in order to incorporate issues such as the criticality of a medicine, increasing safety stocks and possible case-by-case analysis, as part of decision making going forward: “I think pharmacy is in a very good position to make these decisions, but that should be done in conjunction with the managers of the hospital.” (Hospital Pharmacist, UK).
Interviewees expressed their concern in relation to not sharing data on risk assessment outcomes or results among key stakeholders, viewing it as another challenge in spreading a culture of performing risk assessment.
Interviewees from Germany and Malta particularly expressed their concern in relation to not sharing data on risk assessment outcomes or results among stakeholders. Whilst currently not in place, an incident reporting system has been noted as being necessary in Italy in order that HCPs from all healthcare facilities may share data among themselves, as to be able to perform risk assessment accordingly. In the context of having a transparent process of risk assessment, it was noted that “if you want to reduce risks, you need to disclose them and present existing risks to the stakeholders, which calls for action” (Hospital Pharmacist, Switzerland).
Communicating the risk assessments performed appeared to be conducted via various routes. Most of the interviewees stated that the internal communication dealing with medicine shortages, including potential risks, is usually carried out via the intranet, emails, electronic prescribing systems/Computerized Physician Order Entry (CPOE), and sometimes via phone calls. These included email, calls, websites, and other official means of information exchange, which is currently not perceived as efficient by a majority of the interviewees. Nevertheless, it is seen as an important tool in managing shortages successfully due to the time-sensitive nature of the information being communicated. Being of this opinion, however, does not mean that all information is shared equally across cultural lines: “I think we share a lot, but not everyone shares the same information, but we are sharing. I'm not sure if this a culture thing.” (Hospital Pharmacist, Malta) and “It's not really exchange. Maybe, it's still somehow old culture, not to tell, not to say…” (Hospital Pharmacist, Latvia). It was also stated in Italy that the regular exchange of information among stakeholders on incidents provoked by shortages is mandatory and is integrated into their quality assurance systems and enforced through policy measures.
There are also ongoing initiatives by HCP bodies to organize separate channels of communication to better suit their needs building on current concerns and challenges: “I think you have to share the information, that's not discussion about that. However, not everybody needs every information. You need to choose a different language.” (Hospital pharmacist, Austria). Initiatives include organizing lectures for patients in order to provide them with more information on their medical treatment. Overall, the way all stakeholders share information and communicate with each other on detected risks due to shortages should be carried out in a more transparent and structured way.
Interviewees cite a number of reasons to implement risk assessment; chiefly among these include (i) providing as many patients as possible with adequate medical treatment; (ii) assuring the treatment's continuity; and (iii) avoiding medical errors and increasing the patient's safety through incorporating risk assessment into quality measurement systems.
The principal factors determining the success rate of risk assessments in a medicine shortage were knowledge of risk assessment techniques, data reliability, and communicating risk assessment output among stakeholders. The barriers also faced when applying risk assessment were identified throughout the interviews in
Barriers along the process of risk assessments.
Challenges and solutions for overcoming barriers in applying risk assessment in shortages.
Financial resources | Difficulties in obtaining funding for hiring experts in risk assessment, train healthcare professionals in this field and provide additional working hours specifically dedicated to shortages | Provide sufficient funds to carry out risk assessment in order to prevent more costly drug adverse effects that need to be mitigated due to improperly mitigated shortages |
Human resources | Lack of experts in the field of risk assessment among healthcare professionals | Provide training on risk assessment techniques with real case examples in shortages |
Data accessibility and sharing | Not having timely, precise and reliable information and feedback from all stakeholders involved in shortages processes | Provide means for open and transparent communication across healthcare sectors including local healthcare setting environment |
Retrospective risk assessment | Reactively treating emerging risks | Using retroactive approach only for recording trends and not for overall risk analysis |
Prospective risk assessment | Not being able to incorporate all potential risks that might occur within a holistic risk assessment process | Involve a thorough sub-processes analysis in order to capture an overall risk assessment |
Multidisciplinary/multi-stakeholder perspective in risk assessment | Lack of willingness for healthcare professionals to take the role in multidisciplinary work on shortages including insufficient stakeholder engagement | Increase safety culture and provide educational incentives |
Internal risk assessment output communication | Lack of IT infrastructure and internal standard operating procedures in place | Introduce clear SOPs and improve IT infrastructure |
External risk assessment output communication | Separate risk assessments conducted by stakeholder | Coordinated multi-stakeholder task group activities with shared risk outputs |
Risk assessment output communication to patients and/or caregivers | Insufficient or no transfer of information on a substitute's efficiency or adverse events profile to patients | Introduce clear SOPs and educate healthcare professionals on communication strategies with patients and/or caregivers during shortages |
Most interviewees (particularly from Latvia, Belgium, and Croatia) recognized risks related to overdosing, or sub-dosing of patients, after substitution taking place due to differences in the alternative's strength and the pharmaco-technological form applied. Furthermore, interviewees agreed that new drug-drug interactions may emerge after introducing a substitute. As stated by an interviewee from Serbia, inappropriate medicine substitution that is solely led by availability may result in worsening health outcomes in general or increased antimicrobial resistance, which is a global concern (
Beyond placing undue financial burdens on a healthcare system and its patients, medicine shortages also bear a significant impact on patient treatment, affecting their health outcomes via delaying or interrupting treatment or enforcing application of less efficient treatment (
Overall, the findings point to the need for wider multi-stakeholder engagement and guidance concerning ways to mitigate shortages in the future. This includes risk assessment in line with guidance from key groups in the US to manage the impact and forces that drive shortages (
It would appear that even mandatory (i.e., enforced by the law) information to be shared on shortages are not equally and timely disseminated among stakeholders (
Moreover, there is a distinct concern regarding medicine shortages when detailed management and mitigation guidance is lacking from higher authorities (
Risk assessment, as a concept in increasing preparedness for medicine shortages and ameliorating their health impact, is usually conducted by the manufacturers addressing production and quality control risks (
Doing so should also be within the remit of the NCAs that should closely coordinate via addressing issues related to data sharing, conducting best practices, and developing strategies, all in order to provide a safe environment for medicine application across Europe and throughout the European regulatory system for medicines (
The ASHP guidelines state that pharmacists should carry out available stock assessment in relation to usage patterns and duration of shortages as well as undertake impact assessments embodying all the elements of risk assessment (
A typically distinct lack of time and financial resources is an ongoing issue when seeking to apply risk assessment strategies in hospitals, which is hindered by a lack of publications characterizing and quantifying the impact of shortages on HCP practices, patient health, and overall costs as well as practices leading to them (
One of the most important aspects of prospective risk assessment emphasized by the interviewees is communication between the stakeholders and HCPs involved in this process, which is currently subject to variation. DTCs and dedicated shortage task force teams are considered essential in trying to communicate data efficiently in healthcare settings and avoid problems encountered by outdated information (
There is also the evident critical need to share the outputs of risk assessment to enhance uptake of such strategies along with general communication regarding shortages in accordance with numerous mitigation guidelines across countries (
There has been growing demand among hospital pharmacists for more timely and accurate information on shortages to better support patient treatment. In order to attain more reliable and accurate information, it would be recommendable that all actors in the supply chain incorporate their own data on shortages into a whole that would better foresee potential shortages on the horizon and communicate them with one another. The immediate advantages of such a measure would be that the individual actors would be able to detect a shortage as it appears (
Ultimately, risk assessment performed on medicine shortages should reach the public in a comprehensive manner and address their concerns. One of the biggest patient concerns is when a medicine will be available in order not to have their care compromised or delayed, especially if a substitute intended to be used may ultimately prove less effective (
Although this study is qualitative in nature and reports chiefly on the current views and perceptions of those who are working as hospital pharmacists in how they mitigate medicine shortages and where they could see improvement in practices, the study does not incorporate other viewpoints from a wider variety of stakeholders involved in addressing medicine shortages on European scale. As such, there is a predefined limitation of what the study may conclude. More comprehensive studies that seek to address risk assessment in order to mitigate medicine shortages must include a wider range of stakeholders; however, such a limitation also points to the path that multi-stakeholder engagement should take in future.
Prospective risk assessment gained more attention in recent years with patient safety set as a priority. Whilst HCPs are aware of the importance of risk assessment as well as available official sources of information regarding methodology, there is currently a lack of knowledge and skills on how to apply risk assessment in everyday practice. Moreover, the data needed for a proper assessment of the risks posed by medicine shortages is currently not provided in a timely-enough manner, which is essential should successful mitigation be achieved. In future, risk assessment should be carried out more in a prospective fashion so that emerging risks from shortages may be better prevented before they even occur. Notwithstanding, this concept of assessing risk is still not widely practiced in the area of shortages and needs to be urgently addressed to better equip HCPs with the tools they need to manage growing medicine shortages worldwide.
Although the process of prospective risk assessment is often considered to be time-consuming and not appropriate for every single shortage, it is necessary, especially for emergency medicines. In addition, the impact of shortages is not very well-documented. Both these challenges need to be addressed as being able to quickly react to an emerging shortage is considered one of the benefits of prospective risk assessment.
All datasets generated for this study are included in the article/
Ethical approval was obtained from the Institutional Review Board (IRB) of the University of Belgrade, Faculty of Pharmacy including the use of the verbal consent procedure (Nb. 1221/2). Verbal agreement from all interviewees was also obtained.
NM designed and carried out the interviews and compiled the first draft and the subsequent iterations of the manuscript. NM and EO performed data analysis and interpretation needed for the manuscript. AA, BG, BM, EO, IH, MK, and TB contributed to critical analysis and interpretation of data as well as revised the manuscript. All authors read, commented on and contributed to the manuscript.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
This research was facilitated throughout the collaboration within COST Action CA 15105 [European Medicines Shortages Research Network—addressing supply problems to patients (Medicines Shortages) and European Association of Hospital Pharmacists (EAHP)]. We would also like to thank to all the interviewees for their active involvement and contributions during this research.
The Supplementary Material for this article can be found online at: