Failure of international translation

International reporting and learning comparable with other high-risk industries has long been the goal of patient safety.18 Realising a system that allows fast and translatable knowledge to prevent error is common in aviation and other services where risk is a daily quantifiable experience. However, healthcare has yet to live up to this standard.

In 1994, 26 years after the first intrathecal vincristine death, the first international advisory was issued by the World Health Organization.19 This followed the Food and Drug Administration of the USA notifying the WHO of multiple case reports that had been accumulating internationally. The WHO reported that these events had been eliminated in the USA since 1991 due to improved labelling requirements recommended by the FDA. The UK Medicines Control Agency implemented a safety scheme involving a colour-coding mechanism after a death in 1990.

The next case in the USA in 1995 became the first reported long-term survivor (a 6-year-old boy who suffered permanent neurological dysfunction of the bladder),20 although one previous case had survived to 3 months and died from their illness rather than the error.14

The next published case in the UK in 1997 was the second long-term survivor (likely because of aggressive neurosurgical treatment). She was a 10-year-old girl left with lower-limb paraplegia.21 Other international reports around this time came from Australia and Singapore as recorded in a chronological summary in 2005 by the Society of Hospital Pharmacists of Australia.22

Failure to achieve compliance with safety guidance

In the mid 1990s, the patient safety movement expanded in some countries' health systems. The publication of the report: To Err is Human by the Institute of Medicine in the USA was a landmark.23 This report scoped the scale of medical error, explained the underlying concepts and encouraged systems thinking as well as setting goals for harm reduction. It attracted public as well as professional interest.

In 1998, a Medication Safety Alert on intrathecal medication was released by the Institute for Safe Medication Practices,24 a body devoted to patient safety and which had previously issued advice related to vincristine in the early 1990s. This was in response to another death in the USA following the FDA guidelines in 1991.25

Despite the advent of patient safety alerts, four more incidents occurred in Canada, Saudi Arabia, Korea and the USA.26–28 Another alert was issued by the ISMP in 2000.29 They announced that the FDA and ISMP would be intensifying efforts to prevent this error in the USA. Two more deaths were reported in the USA in 2003 and 2005.30

Failure of investigations and enquiries

The UK report, An Organisation with a Memory, featured as one of its case studies the intrathecal vincristine error.31 However, before the implications of this initiative were to be fully realised, an 18-year-old boy, Wayne Jowett, died in Nottingham, England in 2001. This led to the largest and most innovative investigation of an intrathecal vincristine incident.

In the Nottingham case, a skilled non-medical accident investigator was called in. He catalogued over 40 weaknesses in the hospital system that led to the fatal error.32 This report remains the most authoritative investigation of such an incident anywhere in the world and reveals this source of catastrophic error as a classic multifactorial system failure. This validated the prevailing scientific theory of patient safety—that medical error is largely due to system failure. A separate UK report to specifically prevent the error was produced by a specialist in the field later the same year.33

In the UK, the intrathecal medication protocols require multiple safeguards to be put in place, reflecting the system nature of the error. The UK also analysed the real stories of harm caused to patients and their families; this included the stories of the first and last patients to die due to intrathecal vincristine in the UK, Lee Duggins in 1976 and Wayne Jowett in 2001.34 A similar approach was adopted by the WHO.35

However, despite this renewed focus on the ‘system error,’ the promotion of a ‘no blame’ culture and the galvanising of patient champions, deaths continued, and individual doctors faced consequences. Following the death of Wayne Jowett, the supervising doctor was suspended and charged with manslaughter.36 37 This was not the first time legal action had been taken against doctors. Two doctors had been charged with manslaughter in 1991,38 their actions described as: ‘momentary, but untypical recklessness.’ An appeal in 1993 failed. The medicolegal aspects appeared in a brief discussion following the death of a women in Singapore in 1996.39

Failure of solutions

Wrong route delivery medication errors can be prevented in three principal ways (box 1).

First, learning from previous adverse events has been slow and has not abated the frequency of error. Issuing drug alerts both nationally and internationally has failed to reliably drive improvements. It raises awareness but lacks the power to enforce change.

Second, although a protocol-driven approach to preventing intrathecal vincristine has defined the 21st-century approach to delivery, this has not halted the error. Multiple government agencies and bodies, nationally and internationally, have published extensive protocols and guidance on safe vincristine delivery as well as debate in medical literature covering multiple health professions.5 22 29–33 40–50 However, incidents have continued to occur on a regular basis, including Spain and Germany.51 52

In 2004, in the UK, implementation of the guidance for the safe administration of vincristine was reviewed.53 Three years after revised protocols and guidance were issued and widely disseminated, all hospitals reported compliance with national guidelines. Yet, an independent review revealed that only 50% were actually compliant. Guidelines and protocols offer healthcare institutions and medical practitioners the opportunity to reduce risk by using professionally agreed and industry-standard operating procedures, but responsibility and management are required by the user to change practice.

Third, there have been attempts to create delivery systems whereby intravenous and intrathecal drugs can only physically be given by their designated routes. Yet, international standards and a mosaic of different tubal connection possibilities within and between countries have kept this seemingly simple solution at bay. The WHO has set the challenge to make it: ‘physically impossible to attach an intravenous syringe containing vincristine to a spinal needle (‘lock and key design’).’49 This represents a forcing function making it virtually physically impossible to take the wrong action. This has had success in other areas—for example, the antihypoxic connections and devices for anaesthetic machines. The Spinal Injection Safety System developed in Canada has shown some promise but has not yet been used widely.47

The luer multicompatible connection system is used commonly in the UK National Health Service. The Department of Health in the UK has been pursuing a plan to implement a system to eliminate all Luer connections associated with spinal delivery systems. This initiative has progressed slowly due to the complexities of designing an entirely new connection system.54 Manufacturers have also been reluctant to invest in development when they believe there is little demand and no major market for a new product. To date, to our knowledge, no data exist comparing the cost of implementing a design solution throughout an entire health system versus the costs of continued medication errors. Yet, it has been reported that in Japan, following the death of a patient, a significant change was made to connectors on syringes in under a year.48

In recent years, the use of a minibag to deliver vincristine has become increasingly discussed and advocated.22 30 40 41 43 44 46 49 50 This is not a full physical design solution or forcing function but offers an attractive interim measure. It involves not using syringes to deliver vincristine at all and instead diluting the drug in a minibag, working on the premise that it would be virtually impossible to deliver this to a patient through a spinal needle. An alert issued by the National Patient Safety Agency in 2008 discovered that no incidents had been reported where a minibag had been used.50 The ISMP conducted a survey attracting 418 responses in December 2005. It determined that a quarter of respondents used minibags.55 However, as the error remains rare, it cannot be regarded as a definitive solution.

The WHO, in its latest drug alert on safe delivery of vincristine, has recommended using the minibag to prevent errors in the absence of a formal design solution which separates intravenous and intrathecal routes physically.49 The WHO published the alert immediately following the death of a patient in Hong Kong in July 2007. The Hong Kong Hospital Authority held an enquiry and later changed its policy to use the minibag for vincristine delivery.5 However, the minibag is not yet used everywhere.

Emergence of a new source of harm

Error-prone situations always continue to elude and surprise. In China, in 2007, the drug company Shanghai Pharmaceutical Group contaminated, at the factory level, methotrexate and cytarabin hydrochloride (drugs normally given intrathecally) with vincristine.56–60 The Chinese government recalled the drugs and closed the plant. At first, a few children in Shanghai and Guangxi Zhuang Autonomous Region suffered neurological symptoms. Eventually the outbreak was believed to have led to 193 patients nationwide having intrathecal vincristine unintentionally as part of their normal medication plans. Paralysis was common, and these incidents increased the world total from 58 to 251 overnight. The company has previously exported drugs to 70 countries worldwide.

Unusual events like this are outwith the scope of any existing error reporting system, and even the best design solution would not prevent such an unpredicatble and ‘upstream’ form of error. Yet, these events keep us alert to the inherent dangers in every healthcare establishment and add another vulnerability to this long-running story of unsafe care.