August 11, 2011 — In nearly one third of cancer patients receiving erythropoiesis-stimulating agents (ESAs) in the United States, the use of the blood-cell-boosting agents was either too short or too long, according to the authors of a study that used data from the Surveillance, Epidemiology, and End Results–Medicare database from 1995 to 2005.
The findings, published online August 1 in the Journal of Clinical Oncology, raise concerns about inappropriate use, wasted healthcare resources, and patient safety, given the black-box warning that accompanies these drugs, say the authors, led by Jason Wright, MD, from Columbia University Medical Center in New York City.
ESAs are indicated for the treatment of anemia in cancer patients receiving myelosuppressive chemotherapy that is not curative; US Food and Drug Administration (FDA) approval of both epoetin alfa and darbepoetin was based on clinical trials that assessed 12 weeks of treatment.
Of the 21,091 patients the study authors analyzed, 5,099 (24.2%) received ESAs for 1 week or less, which the authors called "misuse," and 1,601 (7.6%) received ESAs for more than 14 weeks, which was termed "prolonged use."
The study authors say their goal was to document such "clearly inappropriate" use of ESAs by American clinicians.
However, an expert not involved with the study believes the analysis misses its mark.
"Preventing transfusions is the only criteria for judging inappropriate or appropriate use," said David Kuter, MD, chief of hematology at the Massachusetts General Hospital in Boston.
Dr. Kuter explained that FDA labeling is based on initial studies and does not always meet all clinical circumstances. For instance, the 3-month maximum use for ESAs might fall short of an individual patient's needs. "Many patients require longer-term therapy — more than 3 months," he told Medscape Medical News. "Some chemotherapy is 6 months long," he added. "Prolonged use is not necessarily inappropriate."
Furthermore, the use of ESAs for a week or less may "reflect the inability to secure payment," a "patient's desire not to be injected," or other difficulties, he said. "You have to ask why that situation arose," explained Dr. Kuter about such short-term use. The study does not do that, he added. "Doctors realize this is a chronic therapy," he noted, suggesting that some portion of what the study authors call misuse reflects circumstances outside the scope of the analysis.
Off-Label Use
The study also reveals the dimensions of off-label use of ESAs. The authors found that the administration of ESAs after chemotherapy has ended, which is not indicated in the labeling, occurred in 2,876 patients (13.6% of the total studied). Once again, Dr. Kuter noted that such use "might be justified if it could avoid transfusions."
Finally, Dr. Kuter suggested that the study period (1995 to 2005) skews the findings. The safety risks, which include shortened overall survival and disease recurrence/progression in a variety of cancers, "were not apparent at the time of the study," he said.
The study authors acknowledge this limitation. "Given the widespread recognition of the safety concerns of ESAs, patterns of use have likely shifted in the past 5 years. More studies are clearly warranted to examine the influence of new regulations on ESA use," they write.
Another Concern: Conflict of Interest
The use of ESAs in the United States increased by 340% from 2001 to 2006, say the authors. The estimated annual Medicare expenditure is more than $1 billion, they add. Thus, there are both cost and safety concerns with these agents.
To get a better handle on patterns of use among oncologists, the investigators looked at Medicare patients who had breast, nonsmall-cell lung, or colon cancer. "These cancers were thought to represent common cancers for which ESAs are frequently used," write Dr. Wright and colleagues.
They then matched treating physicians with ESA claims, and attempted to characterize the physicians who were more or less likely to be inappropriately using the drugs.
Their findings include the facts that:
"It also seems likely that economic considerations play a role in the allocation of ESAs," they write. Citing a survey of oncologists (Am J Med. 2004;116:28-34), the authors say that 37% of physicians in the United States reported that financial considerations affect their decision to use ESAs. "The current system in which private-practice physicians purchase ESAs and generate profit from their administration has raised concerns regarding conflicts of interest," they summarize.
Dr. Kuter has similar concerns. "Doctors have been aggressive because you could make money off each injection," he explained. But he also said that the study is not proof of that. "The paper doesn't provide strong evidence that money was a strong motivator."
The FDA is attempting to improve evidence-based use of ESAs, say the authors, with efforts that include a risk evaluation and mitigation strategy that is unique to these drugs. Also, they note that ESA reimbursement "has been limited in the United States" in an effort to control costs.
The study was supported by a grant from the National Cancer Institute. One of the coauthors reports serving as a consultant or advisor to Amgen.
J Clin Oncol. Published August 1, 2011. Abstract
The findings, published online August 1 in the Journal of Clinical Oncology, raise concerns about inappropriate use, wasted healthcare resources, and patient safety, given the black-box warning that accompanies these drugs, say the authors, led by Jason Wright, MD, from Columbia University Medical Center in New York City.
ESAs are indicated for the treatment of anemia in cancer patients receiving myelosuppressive chemotherapy that is not curative; US Food and Drug Administration (FDA) approval of both epoetin alfa and darbepoetin was based on clinical trials that assessed 12 weeks of treatment.
Of the 21,091 patients the study authors analyzed, 5,099 (24.2%) received ESAs for 1 week or less, which the authors called "misuse," and 1,601 (7.6%) received ESAs for more than 14 weeks, which was termed "prolonged use."
The study authors say their goal was to document such "clearly inappropriate" use of ESAs by American clinicians.
However, an expert not involved with the study believes the analysis misses its mark.
"Preventing transfusions is the only criteria for judging inappropriate or appropriate use," said David Kuter, MD, chief of hematology at the Massachusetts General Hospital in Boston.
Dr. Kuter explained that FDA labeling is based on initial studies and does not always meet all clinical circumstances. For instance, the 3-month maximum use for ESAs might fall short of an individual patient's needs. "Many patients require longer-term therapy — more than 3 months," he told Medscape Medical News. "Some chemotherapy is 6 months long," he added. "Prolonged use is not necessarily inappropriate."
Furthermore, the use of ESAs for a week or less may "reflect the inability to secure payment," a "patient's desire not to be injected," or other difficulties, he said. "You have to ask why that situation arose," explained Dr. Kuter about such short-term use. The study does not do that, he added. "Doctors realize this is a chronic therapy," he noted, suggesting that some portion of what the study authors call misuse reflects circumstances outside the scope of the analysis.
Off-Label Use
The study also reveals the dimensions of off-label use of ESAs. The authors found that the administration of ESAs after chemotherapy has ended, which is not indicated in the labeling, occurred in 2,876 patients (13.6% of the total studied). Once again, Dr. Kuter noted that such use "might be justified if it could avoid transfusions."
Finally, Dr. Kuter suggested that the study period (1995 to 2005) skews the findings. The safety risks, which include shortened overall survival and disease recurrence/progression in a variety of cancers, "were not apparent at the time of the study," he said.
The study authors acknowledge this limitation. "Given the widespread recognition of the safety concerns of ESAs, patterns of use have likely shifted in the past 5 years. More studies are clearly warranted to examine the influence of new regulations on ESA use," they write.
Another Concern: Conflict of Interest
The use of ESAs in the United States increased by 340% from 2001 to 2006, say the authors. The estimated annual Medicare expenditure is more than $1 billion, they add. Thus, there are both cost and safety concerns with these agents.
To get a better handle on patterns of use among oncologists, the investigators looked at Medicare patients who had breast, nonsmall-cell lung, or colon cancer. "These cancers were thought to represent common cancers for which ESAs are frequently used," write Dr. Wright and colleagues.
They then matched treating physicians with ESA claims, and attempted to characterize the physicians who were more or less likely to be inappropriately using the drugs.
Their findings include the facts that:
- Private-practice physicians (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.72 to 0.84) and high-volume physicians (OR, 0.78; 95% CI, 0.72 to 0.85) were less likely to use 1 week or less of ESA treatment.
- Treatment by high-volume oncologists (OR, 1.33; 95% CI, 1.14 to 1.55) and by oncologists who graduated from American medical schools (OR, 1.26; 95% CI, 1.12 to 1.42) predicted prolonged-duration ESA use, whereas female oncologists (OR, 0.79; 95% CI, 0.68 to 0.93) were less likely to prescribe prolonged ESA treatment.
- Private-practice physicians (OR, 1.18; 95% CI, 1.02 to 1.38) and high-volume providers (OR, 1.58; 95% CI, 1.33 to 1.87) were more likely to prescribe more than 24 weeks of ESA treatment.
"It also seems likely that economic considerations play a role in the allocation of ESAs," they write. Citing a survey of oncologists (Am J Med. 2004;116:28-34), the authors say that 37% of physicians in the United States reported that financial considerations affect their decision to use ESAs. "The current system in which private-practice physicians purchase ESAs and generate profit from their administration has raised concerns regarding conflicts of interest," they summarize.
Dr. Kuter has similar concerns. "Doctors have been aggressive because you could make money off each injection," he explained. But he also said that the study is not proof of that. "The paper doesn't provide strong evidence that money was a strong motivator."
The FDA is attempting to improve evidence-based use of ESAs, say the authors, with efforts that include a risk evaluation and mitigation strategy that is unique to these drugs. Also, they note that ESA reimbursement "has been limited in the United States" in an effort to control costs.
The study was supported by a grant from the National Cancer Institute. One of the coauthors reports serving as a consultant or advisor to Amgen.
J Clin Oncol. Published August 1, 2011. Abstract
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