A little over a year and a half has passed since shortages of preservative-free methotrexate threatened the ability of oncologists to treat children with acute lymphoblastic leukemia and osteosarcoma.
As noted by Michael P. Link, MD, past president of the American Society of Clinical Oncology (ASCO), it took “heroic efforts” by the US Food and Drug Administration’s Office of Drug Shortages to help prevent “a catastrophic situation.” But, he added in an article published in the ASCO Daily News during the recent ASCO annual meeting in Chicago, “the underlying problems have not yet been addressed.”
Just how serious is the issue? Link cites an article he co-authored last year that was published in The New England Journal of Medicine, on the consequences of substituting cyclophosphamide for mechlorethamine in management of pediatric Hodgkin lymphoma. Mechlorethamine is part of the 12-week Stanford V chemotherapy regimen that evolved from the MOPP regimen for treating Hodgkin lymphoma. A shortage of mechlorethamine in 2009 forced clinicians to substitute cyclophosphamide. A subsequent retroanalysis compared the likelihood of event-free survival among 181 patients treated with the original regimen including mechlorethamine, with that of 40 patients treated with the regimen that substituted cyclophosphamide. “The study found that 88% of patients treated with the established regimen were expected to be event-free survivors at 2 years, compared to only 75% of those treated with the cyclophosphamide-containing regimen.”
Although shortages of chemotherapy agents “might have eased very slightly” in recent months, Link says oncology practices are still often forced to make substitutions. “In addition, physicians are concerned with the shortage of non-chemotherapy drugs and solutions (supportive care) that are critical for patient care,” such as anti-emetics, pain medications, basic IV fluids, and electrolytes. “When oncologists are forced to switch from standard regimens, they often have to substitute a more expensive drug for the one in short supply, adding to patient anxiety and the costs of care, and potentially resulting in inferior patient outcomes.”
And therein lies the rub. The Government Accountability Office is looking into the causes of the shortages, “and we hope its assessment will help guide future efforts to prevent shortages,” says Link. But one major cause is obvious, and perhaps it is the Achilles' heel of efforts to contain costs in the crazy quilt healthcare system of ours: Pharmaceutical companies, private hospitals, device manufacturers, and medical practices, all operate under a business model based on the necessity of making profits.
A pharmaceutical company does not spend millions upon millions of dollars to develop a new drug only to see an older, inexpensive, generic drug used instead. This is why incentives are required to encourage development of “orphan” drugs to treat diseases that affect a small part of the population.
Other factors contribute to shortages, too. ASCO, says Link, will continue to survey its members and “call on Congress to convene a blue ribbon panel that includes providers, manufacturers, suppliers, FDA representatives, and patients to develop comprehensive legislation to resolve this issue. We have made too much progress in cancer management in the past 50 years to be hindered by shortages of relatively inexpensive, mostly older drugs that have been in use from the early days of oncology.”
He is right of course. But I hope he and ASCO have some other ideas besides asking Congress to fix the problem. The way Congress is behaving now, they might just find a way to make things worse.