Keeping Cures on the Shelf

Regulatory action has been taken to address the problem of drug shortages for pediatric cancer patients. However, there is still more work to be done.

During 2010 and 2011, the news headlines were filled with chilling stories of drug shortages. Patients and physicians were fearful that critical medications would be unavailable, pharmacists were rationing supplies, and regulators were combing the globe for additional stocks. During this crisis, policymakers around the world were trying to understand the reasons for this phenomenon and respond appropriately.
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In an attempt to address the problem, the White House issued an executive order to require early notification of disruptions by producers in 2011.1 That was followed by a more rigorous response in 2012, with the enactment of the Food and Drug Administration Safety and Innovation Act (FDASIA),2 which required increased notifications. Then in 2013, the FDA developed a drug shortage strategic plan to coordinate early notification and response among a wide array of domestic and international stakeholders and devoted more of its resources to monitoring and managing the problem.3 Regulators now have in place supply line tripwires that provide for early notification by manufacturers and distributors as well as priority structures to fill gaps. The result of these efforts have been significant. Whereas there were 251 shortages reported in 2011 and 117 in 2012, only 26 were reported in 2015.4

The causes of shortages are varied and difficult to anticipate or address. Many have been quality and manufacturing issues, such as problems with sterility and contamination. Some have been simply production run problems, but many have also been marketplace dislocations, for example, companies making commercial decisions about the most profitable drugs to produce. If a company manufactures a drug and has developed and won approval for another drug that costs more, there is every reason to stop producing the older, cheaper drug.

Consequently, drug shortages continue to plague the health care system. One of the most vulnerable populations to these occurrences has been that of pediatric cancer patients. The types of drugs that have been susceptible to shortage are invariably generics. They have also tended to be sterile injectable drugs, many of which are used in chemotherapy, anesthesia, injectable nutritional medications, and other acute medications.5 Because the backbone regimen of treating pediatric patients consists of older drugs, which have become either low price or generic, the threat of shortage is serious and potentially life-threatening for these patients.

Additionally, because there are only ~15,000 childhood cancer patients per year,6 manufacturers have little interest in producing new specialized drugs for such a limited market. Precision medicine has yet to penetrate childhood oncology to the extent that it has for adults.

Drug availability also influences whether clinical trials can be conducted successfully. Childhood cancer patients are vulnerable to variations in protocols because a large percentage of children are treated in National Cancer Institute–sponsored or institutional clinical trials.

The prospect of a physician having to tell desperate parents that there is a shortage of a critical drug needed for the treatment of their child is a difficult and traumatic dilemma. With limited stocks, physicians managing a number of patients are faced with ethical choices that ultimately require selective rationing. Doctors in the pediatric cancer community have begun to frame a matrix for balancing these choices. But these are choices that are unique to the United States among nations in the developed world, and they continue to challenge doctors, administrators, industry, regulators, and families.

The Children’s Cause for Cancer Advocacy (www.childrenscause.org), which is solely focused on policy solutions to improve the treatment and care of childhood cancer patients and survivors, has been intimately involved in this issue. The organization has actively promoted provisions in the FDASIA that addressed drug shortages and has worked to incentivize the development of new treatments for children with cancer. Children’s Cause promoted early notification by industry to potential supply disruptions as well as policies to ensure that wholesalers and hospital pharmacies monitor and report on inventories, and importantly, that patients and the public be given the opportunity to report shortages that have affected them or their families.

Ultimately, however, the mitigation of drug shortages will be the result of vigilance on the part of all stakeholders. Maintaining that awareness and managing a quick response system requires that doctors and families become involved in the policy process that makes it work and the rapid reporting of individual instances. Children’s Cause offers families a way to become effective advocates and to improve the policy process by participating in the Kids Action Network (http://www.childrenscause.org/kan/) and encourages childhood cancer advocates, families, survivors, and doctors to join with us to ensure that the best treatments for kids are fully stocked and accessible. 

For another perspective on this issue, read the Viewpoint, "Chemotherapy Shortages: When is Enough, Enough?," by Yoram Unguru, MD, MS, MA. 

References

1.    Executive Order 13588 – Reducing Prescription Drug Shortages. October 31, 2011. https://www.gpo.gov/fdsys/granule/CFR-2012-title3-vol1/CFR-2012-title3-vol1-eo13588

2.    Food and Drug Administration Safety and Innovation Act. Public Law 112-144. 112th Congress. July 9, 2012. https://www.gpo.gov/fdsys/pkg/PLAW-112publ144/pdf/PLAW-112publ144.pdf

3.    US Food and Drug Administration. Strategic plan for preventing and mitigating drug shortages. October 2013. http://www.fda.gov/downloads/Drugs/DrugSafety/DrugShortages/UCM372566.pdf

4.    Jensen V. Preventing and mitigating drug shortages—FDA’s and manufacturers’ roles. fda.gov website. http://www.fda.gov/downloads/Drugs/NewsEvents/UCM493617.pdf. Accessed April 19, 2016.

5.    US Food and Drug Administration. Drug Shortages Infographic. fda.gov website. http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm441579.htm. Updated April 10, 2015. Accessed April 19, 2016.

6.    CureSearch for Children’s Cancer. Number of Diagnoses. CureSearch website. http://curesearch.org/Number-of-Diagnoses#. Accessed April 19, 2016.

7.    Unguru Y, Fernandez CV, Bernhardt B, et al. An ethical framework for allocating scarce life-saving chemotherapy and supportive care drugs for childhood cancer [published online ahead of print January 29, 2016]. J Natl Cancer Inst. doi: 10.1093/jnci/djv392.