Post COVID availability of oncology drugs – Is this the new normal on both sides of the Atlantic?

The World Health Organisation describes medicine shortages as an ongoing health crisis where there is a lack of access to medicines in both hospitals and pharmacies affecting all countries independent of their income level. ¹ Although drug shortages are not a new phenomenon, their prevalence has significantly increased over the last 5 years, particularly during and post the COVID-19 pandemic. ¹ This has triggered international concern over the long-term supply of drugs. Any class of therapeutics can be liable to shortage, such as emergency medicines, antineoplastic agents, antimicrobials, analgesics, cardiovascular drugs, hormone replacement therapies (HRTs), radiopharmaceuticals and parenteral products. ² The rationale for worldwide medicine shortages is multifaceted. This has in turn created a highly pressurised environment where the demand for essential medicines exceeds the supply.^2,3 Insufficient quantities of raw materials, legislative barriers, low-profit margins/reimbursement, manufacturing and procurement issues are all reasons why drug shortages can occur. ² Current issues with stockpiling of drugs due to uncertain availability have been compounded by funding complications and the inability to procure adequate quantities of medicines from international markets. ¹ The United Kingdom has been faced with worsening HRT shortages whilst the United States Food and Drug Administration reports supply chain issues with liquid ibuprofen and platinum-based oncology drugs.^4,5 Although global mitigation strategies have been developed to overcome these shortages, patients, pharmacists, clinicians and other healthcare professionals are still affected worldwide.^2,6,7

Drug shortages have been further exacerbated by the long-lasting effects of the COVID-19 pandemic. The pandemic has caused significant supply chain issues for pharmaceutical manufacturers those in the generic drug market. As many anticancer drugs are only available as the generic version, the disruption within this supply chain has affected a substantial number of oncology patients worldwide.^8,9 This sector of the pharmaceutical industry relies heavily upon sourcing the main generic drug or active pharmaceutical ingredients from countries such as Asia, India and China. ²

Often termed as the ‘production bottlenecks’, any supply chain interruptions in these countries will have global consequences. ⁶ The acetaminophen (paracetamol) shortage seen worldwide in 2020 is a clear example of the fractured supply chain that has resulted from China's border closures and India's exportation limitations.

In addition to exhausted reserve inventories the ‘bullwhip effect’ also wreaked havoc on supply chains during and after the pandemic, where unanticipated spikes in demand led to amplified demand variability upstream. ¹⁰ Double-ordering and overstocking have been solutions used by pharmaceutical companies to respond to the rebound in global demand post COVID-19 lockdowns. External factors seen at a local level such as Brexit, the devaluation of the sterling in the United Kingdom and the long-standing US–China trade war have added additional stress to an already fragile system.^11,12

One area of healthcare that has been significantly impacted is cancer care. Access to medicines for cancer patients is crucial for providing ongoing quality care. ¹³ Shortages of cancer drugs in the United States and the United Kingdom have led to challenges in patient care and treatment outcomes. According to a report by the American Society of Clinical Oncology (ASCO), drug shortages have become increasingly prevalent, affecting the availability of critical medications for cancer treatment. ¹⁴ The US Senate Committee on Homeland Security and Governmental Affairs reported in March 2023 that drug shortages are at a record high. ¹⁵ Between 2021 and 2022 new medicine shortages had increased by approximately 30%, with 295 active drug shortages recorded at the end of 2022. ¹⁵ Similar figures have been witnessed in the United Kingdom. As of April 2023, there were 301 drug shortages reported, 100 more than in 2018. ¹⁶ With this number increasing, the topic of drug supply and availability was debated in Parliament on 14th June 2023 where ministers confirmed that the Government will take the necessary steps to guarantee the continued supply and availability of prescription and non-prescription drugs into the United Kingdom. ¹⁶

Current shortages in platinum-based drugs (cisplatin and carboplatin) are amongst the most significant to be affecting cancer patients in the United States; both of which are essential medicines used to treat a diverse range of malignancies including head and neck, gynaecological and gastrointestinal cancers. ¹⁷ The Society of Gynecologic Oncology and ASCO recently issued disease-specific documents (urothelial, breast, gastrointestinal, gynaecologic, head and neck and small cell lung cancer) with evidence-based recommendations for alternative treatment options as a result of these shortages. Unsurprisingly the worrisome scarcity of cisplatin has now reached the United Kingdom. The Department of Health & Social Care issued a tier 2 Medicines Supply Notice on the 13th July 2023 informing pharmacy procurement teams of the shortage, forcing urgent supplies to be obtained through unlicensed imports in order to prevent catastrophic repercussions to patient care.

Furthermore, The Medicines and Healthcare products Regulatory Agency in the United Kingdom released a national notification of product shortage for paclitaxel–albumin in January 2023 which left oncologists in an acute moral dilemma; how to fairly manage or ration pharmacological intervention whilst in a position of lack. ¹⁸ Many clinicians were forced to look for suitable alternatives for both breast and pancreatic cancers. As a result, healthcare providers and patients are now facing ongoing difficulties in accessing essential anticancer drugs leading to modified treatment plans, delayed treatment starts and potentially serious consequences to patient outcomes and survival.^19,20

Concerns over patient safety have also been reported. In the United States, there has been an increase in clinical risk associated with prescribing alternative cancer treatment as a result of drug shortages. ⁹ A national survey completed by hospital oncology and haematology pharmacists reported that the prescribing of alternative agents has led to medication near-misses and errors (16% and 6%, respectively). ⁹ In the United Kingdom, in July 2022, 54% of pharmacists responding to a survey carried out by The Pharmaceutical Journal said that medicine shortages were now putting patient safety at risk. ²¹

While recommended pre-pandemic, the Haematology Oncology Pharmacy Association Standards Committee organised a working group of oncology pharmacist specialists to examine the safety and value of dose rounding of biologic and cytotoxic anticancer agents. This committee concluded that each institution should develop their own dose-rounding policies, with the consideration that both monoclonal antibodies and traditional cytotoxic agents can be dose rounded within 10% of the prescribed dose. ²² This enables cancer centres to maximise the number of patients who are able to receive treatment and reduce waste while inventory is limited. Although the United Kingdom has a national dose banding variance of 6% for traditional cytotoxic agents, if cancer drug shortages continue then the adoption of the US methodology may need to be considered.

The consequences of such cancer drug shortages in both the United Kingdom and US healthcare systems are extensive. Oncology teams are frequently faced with ethical dilemmas where they are expected to make difficult decisions regarding treatment regimens based on drug availability. Physicians are in the ‘unconscionable position’ of being forced to choose who receives the scarce resource and who doesn’t. ²³ This can lead to suboptimal therapy choices and delayed treatments, or the need for drug substitutions with potentially different efficacy or increased toxicities. ¹⁴

Moreover, these shortages place an additional burden on healthcare providers. Pharmacy teams have to invest significant time and resources in managing the logistics of drug allocation and substitution, further straining their workload.^6,24 As described in ‘The NHS SACT capacity crisis: Challenges and Solutions’, hospitals within the United Kingdom have been forced to create capacity by developing innovative ways of utilising a limited workforce to cope with the ever-growing demand for cancer care. ²⁴ Additionally, many US-based healthcare providers have followed the advice of ASCO and enacted Drug Shortage Allocation Committees in the hope of creating a system to meet each new shortage in a fair, equitable and reproducible way. ²⁵ These committees are multidisciplinary in nature and use an ethical framework to guide decision-making for the short-term rationing of drugs. They can override practice-based formulary restrictions and in some circumstances ultimately decide which patients receive treatment.

The impact of cancer drug shortages on patient outcomes is an increasing fear for many healthcare professionals. A study published in the Journal of Oncology Practice examined the effect of drug shortages on patient care and identified that they were associated with increased treatment costs, treatment delays and compromised clinical trial enrolment.^9,26 If healthcare providers fail to deliver curative treatments or defer chemotherapy as a result of drug shortages it can have profound implications for patient outcomes including survival rates and quality of life.^19,20 Patients may also experience heightened psychological distress and anxiety due to uncertainty surrounding their treatment plans.^9,26

The shortage of essential medicines is a growing emergency that requires concerted action at a global level. Critical medicines used to treat cancer are becoming increasingly difficult to source resulting in devastating effects for cancer patients worldwide. The examples highlighted in this paper showcase the United States and United Kingdom market, but these issues are not unique to just these countries. A continued collaborative approach between key stakeholders including international health organisations, manufacturers, wholesalers, pharmacists and other healthcare professionals is vital if long-term strategies to prevent and manage global drug shortages are to be developed and successfully implemented. ¹³