Elizabeth Mechcatie

The Food and Drug Administration on Nov. 7 approved cetuximab as an initial treatment of late-stage head and neck cancer in combination with chemotherapy.

Cetuximab, marketed as Erbitux by Bristol-Myers Squibb, is an epidermal growth factor receptor (EGFR) antagonist, administered as an intravenous infusion. Previously, it was approved in combination with radiation therapy for the initial treatment of locally or regionally advanced squamous cell carcinoma. It was also approved for use alone in patients with recurrent locoregional disease or metastatic disease whose disease has progressed following platinum-based chemotherapy.

The newly approved indication is for the treatment of these recurrent or metastatic patients as an initial therapy in combination with platinum-based therapy with 5-fluorouracil (5-FU), a BMS spokesperson said. (At press time, the company had not yet issued a statement on the approval.)

Erbitux was initially approved in 2004 to treat EGFR-positive late-stage colon cancer after patients stopped responding to chemotherapy and was approved in 2006 for the treatment of head and neck cancer. The newly approved indication is for "recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based therapy with 5-FU," according to the revised label, posted on the FDA Web site.

The two previously approved indications for head and neck cancer were for "locally or regionally advanced squamous cell carcinoma of the head and neck in combination with radiation therapy," and for "recurrent or metastatic squamous cell carcinoma of the head and neck progressing after platinum-based therapy.

"Erbitux’s ability to extend the lives of patients with head and neck cancers is an important tool for oncologists who often rely on a multitreatment approach for patients," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research said in the statement. "Given the aggressive nature of head and neck cancers that cannot be treated with surgery and radiation, it is important that patients have as many treatment options available as possible," he added.

The approval was based on a multicenter study of 442 patients who had metastatic or recurrent head and neck cancer, which was inoperable or widespread, and of those who had not been treated with chemotherapy. The study was conducted outside of the United States and used a version of cetuximab that is not approved in the United States, the statement said.

The median overall survival among patients who were treated with cetuximab and chemotherapy (cisplatin or carboplatin and 5-fluorouracil) combination was 10.1 months, compared with 7.4 months among those who received chemotherapy alone cisplatin or carboplatin and 5-fluorouracil, the FDA statement said.

The most common adverse events reported by patients in the cetuximab plus chemotherapy arm were rash; pruritus; nail changes; headache; diarrhea; and respiratory, skin, and mouth infections, according to the FDA.

Other adverse effects that have been associated with cetuximab include low serum levels of magnesium, potassium, and calcium; and potentially fatal infusion reactions and myocardial infarctions. Sun exposure should be limited during treatment.

Cetuximab available in the United States provides about 22% greater exposure than the European Union–approved cetuximab that was used in this study, but this pharmacokinetic data along with the results of this study "and other clinical trial data establish the efficacy of Erbitux at the recommended dose," according to the revised prescribing information posted on the FDA Web site.

The Food and Drug Administration on Nov. 7 approved cetuximab as an initial treatment of late-stage head and neck cancer in combination with chemotherapy.

Cetuximab, marketed as Erbitux by Bristol-Myers Squibb, is an epidermal growth factor receptor (EGFR) antagonist, administered as an intravenous infusion. Previously, it was approved in combination with radiation therapy for the initial treatment of locally or regionally advanced squamous cell carcinoma. It was also approved for use alone in patients with recurrent locoregional disease or metastatic disease whose disease has progressed following platinum-based chemotherapy.

The newly approved indication is for the treatment of these recurrent or metastatic patients as an initial therapy in combination with platinum-based therapy with 5-fluorouracil (5-FU), a BMS spokesperson said. (At press time, the company had not yet issued a statement on the approval.)

Erbitux was initially approved in 2004 to treat EGFR-positive late-stage colon cancer after patients stopped responding to chemotherapy and was approved in 2006 for the treatment of head and neck cancer. The newly approved indication is for "recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based therapy with 5-FU," according to the revised label, posted on the FDA Web site.

The two previously approved indications for head and neck cancer were for "locally or regionally advanced squamous cell carcinoma of the head and neck in combination with radiation therapy," and for "recurrent or metastatic squamous cell carcinoma of the head and neck progressing after platinum-based therapy.

"Erbitux’s ability to extend the lives of patients with head and neck cancers is an important tool for oncologists who often rely on a multitreatment approach for patients," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research said in the statement. "Given the aggressive nature of head and neck cancers that cannot be treated with surgery and radiation, it is important that patients have as many treatment options available as possible," he added.

The approval was based on a multicenter study of 442 patients who had metastatic or recurrent head and neck cancer, which was inoperable or widespread, and of those who had not been treated with chemotherapy. The study was conducted outside of the United States and used a version of cetuximab that is not approved in the United States, the statement said.

The median overall survival among patients who were treated with cetuximab and chemotherapy (cisplatin or carboplatin and 5-fluorouracil) combination was 10.1 months, compared with 7.4 months among those who received chemotherapy alone cisplatin or carboplatin and 5-fluorouracil, the FDA statement said.

The most common adverse events reported by patients in the cetuximab plus chemotherapy arm were rash; pruritus; nail changes; headache; diarrhea; and respiratory, skin, and mouth infections, according to the FDA.

Other adverse effects that have been associated with cetuximab include low serum levels of magnesium, potassium, and calcium; and potentially fatal infusion reactions and myocardial infarctions. Sun exposure should be limited during treatment.

Cetuximab available in the United States provides about 22% greater exposure than the European Union–approved cetuximab that was used in this study, but this pharmacokinetic data along with the results of this study "and other clinical trial data establish the efficacy of Erbitux at the recommended dose," according to the revised prescribing information posted on the FDA Web site.

The Food and Drug Administration on Nov. 7 approved cetuximab as an initial treatment of late-stage head and neck cancer in combination with chemotherapy.

Cetuximab, marketed as Erbitux by Bristol-Myers Squibb, is an epidermal growth factor receptor (EGFR) antagonist, administered as an intravenous infusion. Previously, it was approved in combination with radiation therapy for the initial treatment of locally or regionally advanced squamous cell carcinoma. It was also approved for use alone in patients with recurrent locoregional disease or metastatic disease whose disease has progressed following platinum-based chemotherapy.

The newly approved indication is for the treatment of these recurrent or metastatic patients as an initial therapy in combination with platinum-based therapy with 5-fluorouracil (5-FU), a BMS spokesperson said. (At press time, the company had not yet issued a statement on the approval.)

Erbitux was initially approved in 2004 to treat EGFR-positive late-stage colon cancer after patients stopped responding to chemotherapy and was approved in 2006 for the treatment of head and neck cancer. The newly approved indication is for "recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based therapy with 5-FU," according to the revised label, posted on the FDA Web site.

The two previously approved indications for head and neck cancer were for "locally or regionally advanced squamous cell carcinoma of the head and neck in combination with radiation therapy," and for "recurrent or metastatic squamous cell carcinoma of the head and neck progressing after platinum-based therapy.

"Erbitux’s ability to extend the lives of patients with head and neck cancers is an important tool for oncologists who often rely on a multitreatment approach for patients," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research said in the statement. "Given the aggressive nature of head and neck cancers that cannot be treated with surgery and radiation, it is important that patients have as many treatment options available as possible," he added.

The approval was based on a multicenter study of 442 patients who had metastatic or recurrent head and neck cancer, which was inoperable or widespread, and of those who had not been treated with chemotherapy. The study was conducted outside of the United States and used a version of cetuximab that is not approved in the United States, the statement said.

The median overall survival among patients who were treated with cetuximab and chemotherapy (cisplatin or carboplatin and 5-fluorouracil) combination was 10.1 months, compared with 7.4 months among those who received chemotherapy alone cisplatin or carboplatin and 5-fluorouracil, the FDA statement said.

The most common adverse events reported by patients in the cetuximab plus chemotherapy arm were rash; pruritus; nail changes; headache; diarrhea; and respiratory, skin, and mouth infections, according to the FDA.

Other adverse effects that have been associated with cetuximab include low serum levels of magnesium, potassium, and calcium; and potentially fatal infusion reactions and myocardial infarctions. Sun exposure should be limited during treatment.

Cetuximab available in the United States provides about 22% greater exposure than the European Union–approved cetuximab that was used in this study, but this pharmacokinetic data along with the results of this study "and other clinical trial data establish the efficacy of Erbitux at the recommended dose," according to the revised prescribing information posted on the FDA Web site.

The Food and Drug Administration has asked manufacturers of tumor necrosis factor blockers to enhance their follow-up of pediatric and young adult patients who develop malignancies while on these treatments.

The agency also is advising health care professionals to “remain vigilant” for malignancies in these patients, according to a statement issued by the FDA Nov. 4.

Manufacturers of TNF blockers have been asked by the FDA to report cases of malignancies in children, adolescents, and adults aged 30 years and younger treated with TNF blockers and to conduct in-depth follow-up of them. They also are asked to provide the agency with annual summaries and assessments of malignancies and data on the use of TNF blockers in these age groups.

“This type of safety surveillance is important for our improved understanding of malignancies in pediatric and young adult patients treated with TNF blockers, because it will allow FDA to more completely capture and analyze all reported malignancies based on more complete and consistent reports,” the agency said in its statement.

The FDA statement updates the agency’s ongoing safety review of TNF blockers and malignancies in children, adolescents, and young adults, and does not include any new cases or previously unrecognized risks associated with TNF blockers in this patient population.

The agency has previously issued reports about the increased risk of lymphomas and other cancers associated with the use of TNF blockers and malignancies in children and young adults in June 2008, August 2009, and most recently, April 2011.

TNF blockers are used to treat Crohn’s disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, and/or juvenile idiopathic arthritis. TNF blockers used in the United States are infliximab (Remicade), etanercept (Enbrel), adalimumab (Humira), certolizumab pegol (Cimzia), and golimumab (Simponi).

Health care professionals also should report these cases to the FDA’s Medwatch program.

The Food and Drug Administration has asked manufacturers of tumor necrosis factor blockers to enhance their follow-up of pediatric and young adult patients who develop malignancies while on these treatments.

The agency also is advising health care professionals to “remain vigilant” for malignancies in these patients, according to a statement issued by the FDA Nov. 4.

Manufacturers of TNF blockers have been asked by the FDA to report cases of malignancies in children, adolescents, and adults aged 30 years and younger treated with TNF blockers and to conduct in-depth follow-up of them. They also are asked to provide the agency with annual summaries and assessments of malignancies and data on the use of TNF blockers in these age groups.

“This type of safety surveillance is important for our improved understanding of malignancies in pediatric and young adult patients treated with TNF blockers, because it will allow FDA to more completely capture and analyze all reported malignancies based on more complete and consistent reports,” the agency said in its statement.

The FDA statement updates the agency’s ongoing safety review of TNF blockers and malignancies in children, adolescents, and young adults, and does not include any new cases or previously unrecognized risks associated with TNF blockers in this patient population.

The agency has previously issued reports about the increased risk of lymphomas and other cancers associated with the use of TNF blockers and malignancies in children and young adults in June 2008, August 2009, and most recently, April 2011.

TNF blockers are used to treat Crohn’s disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, and/or juvenile idiopathic arthritis. TNF blockers used in the United States are infliximab (Remicade), etanercept (Enbrel), adalimumab (Humira), certolizumab pegol (Cimzia), and golimumab (Simponi).

Health care professionals also should report these cases to the FDA’s Medwatch program.

The Food and Drug Administration has asked manufacturers of tumor necrosis factor blockers to enhance their follow-up of pediatric and young adult patients who develop malignancies while on these treatments.

The agency also is advising health care professionals to “remain vigilant” for malignancies in these patients, according to a statement issued by the FDA Nov. 4.

Manufacturers of TNF blockers have been asked by the FDA to report cases of malignancies in children, adolescents, and adults aged 30 years and younger treated with TNF blockers and to conduct in-depth follow-up of them. They also are asked to provide the agency with annual summaries and assessments of malignancies and data on the use of TNF blockers in these age groups.

“This type of safety surveillance is important for our improved understanding of malignancies in pediatric and young adult patients treated with TNF blockers, because it will allow FDA to more completely capture and analyze all reported malignancies based on more complete and consistent reports,” the agency said in its statement.

The FDA statement updates the agency’s ongoing safety review of TNF blockers and malignancies in children, adolescents, and young adults, and does not include any new cases or previously unrecognized risks associated with TNF blockers in this patient population.

The agency has previously issued reports about the increased risk of lymphomas and other cancers associated with the use of TNF blockers and malignancies in children and young adults in June 2008, August 2009, and most recently, April 2011.

TNF blockers are used to treat Crohn’s disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, and/or juvenile idiopathic arthritis. TNF blockers used in the United States are infliximab (Remicade), etanercept (Enbrel), adalimumab (Humira), certolizumab pegol (Cimzia), and golimumab (Simponi).

Health care professionals also should report these cases to the FDA’s Medwatch program.

Prescribers and other stakeholders may submit comments about the Food and Drug Administration’s draft document outlining the main messages to be included in educational programs that will be required for prescribing certain opioid products, the agency announced in the federal register on Nov. 4.

An education program for prescribers and patients is the central component of the Risk Evaluation and Mitigation Strategy (REMS) now required for brand-name and generics of long-acting (LA) and extended-release (ER) formulations of buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone, oxymorphone, and tapentadol. The REMS addresses the risk of abuse and misuse of these products, which has become a major public health problem in recent years. This week, the Centers for Disease Control and Prevention released a report saying the number deaths due to overdoses of prescription pain medications is now greater than is the number of deaths due to heroin and cocaine combined.

REMS is required by the FDA for certain products to ensure that the benefits of a drug continue to outweigh its risks.

Health care professionals who prescribe these products "are in a key position to balance the benefits of prescribing ER/LA opioids to treat pain against the risks of serious adverse outcomes including addiction, unintentional overdose, and death," according to the document, titled "Blueprint for Prescriber Continuing Education."

The blueprint includes sections on assessing patients for treatment; initiating treatment, modifying dosing, and discontinuing treatment; and counseling patients and caregivers on how to use these drugs safely.

The federal register notice says that the agency expects that prescriber training should be provided to prescribers at no cost by "accredited, independent, continuing education providers," funded by "unrestricted grants" from the drug manufacturers.

The deadline for comments on the blueprint is Dec. 4, 2011.

Comments can be submitted electronically or by writing to Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, Md., 20852.

Prescribers and other stakeholders may submit comments about the Food and Drug Administration’s draft document outlining the main messages to be included in educational programs that will be required for prescribing certain opioid products, the agency announced in the federal register on Nov. 4.

An education program for prescribers and patients is the central component of the Risk Evaluation and Mitigation Strategy (REMS) now required for brand-name and generics of long-acting (LA) and extended-release (ER) formulations of buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone, oxymorphone, and tapentadol. The REMS addresses the risk of abuse and misuse of these products, which has become a major public health problem in recent years. This week, the Centers for Disease Control and Prevention released a report saying the number deaths due to overdoses of prescription pain medications is now greater than is the number of deaths due to heroin and cocaine combined.

REMS is required by the FDA for certain products to ensure that the benefits of a drug continue to outweigh its risks.

Health care professionals who prescribe these products "are in a key position to balance the benefits of prescribing ER/LA opioids to treat pain against the risks of serious adverse outcomes including addiction, unintentional overdose, and death," according to the document, titled "Blueprint for Prescriber Continuing Education."

The blueprint includes sections on assessing patients for treatment; initiating treatment, modifying dosing, and discontinuing treatment; and counseling patients and caregivers on how to use these drugs safely.

The federal register notice says that the agency expects that prescriber training should be provided to prescribers at no cost by "accredited, independent, continuing education providers," funded by "unrestricted grants" from the drug manufacturers.

The deadline for comments on the blueprint is Dec. 4, 2011.

Comments can be submitted electronically or by writing to Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, Md., 20852.

Prescribers and other stakeholders may submit comments about the Food and Drug Administration’s draft document outlining the main messages to be included in educational programs that will be required for prescribing certain opioid products, the agency announced in the federal register on Nov. 4.

An education program for prescribers and patients is the central component of the Risk Evaluation and Mitigation Strategy (REMS) now required for brand-name and generics of long-acting (LA) and extended-release (ER) formulations of buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone, oxymorphone, and tapentadol. The REMS addresses the risk of abuse and misuse of these products, which has become a major public health problem in recent years. This week, the Centers for Disease Control and Prevention released a report saying the number deaths due to overdoses of prescription pain medications is now greater than is the number of deaths due to heroin and cocaine combined.

REMS is required by the FDA for certain products to ensure that the benefits of a drug continue to outweigh its risks.

Health care professionals who prescribe these products "are in a key position to balance the benefits of prescribing ER/LA opioids to treat pain against the risks of serious adverse outcomes including addiction, unintentional overdose, and death," according to the document, titled "Blueprint for Prescriber Continuing Education."

The blueprint includes sections on assessing patients for treatment; initiating treatment, modifying dosing, and discontinuing treatment; and counseling patients and caregivers on how to use these drugs safely.

The federal register notice says that the agency expects that prescriber training should be provided to prescribers at no cost by "accredited, independent, continuing education providers," funded by "unrestricted grants" from the drug manufacturers.

The deadline for comments on the blueprint is Dec. 4, 2011.

Comments can be submitted electronically or by writing to Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, Md., 20852.

SILVER SPRING, MD. – With their increasing prevalence, drug shortages in the United States have led to delays in treatment, forced the use of less effective alternatives, and encouraged a burgeoning gray market that sells tough-to-obtain medications at highly inflated prices, according to stakeholders gathered at a recent FDA meeting.

Shortfalls in drug supply have increased in the United States, with 178 shortages of products reported in 2010, up from 61 in 2005, according to Dr. Edward Cox, coordinator of the FDA's drug shortage program. Disproportionately affected are generic drugs and sterile injectable products; the latter accounted for two-thirds of the shortages last year.

About half of the injectable shortages were caused by problems with product quality, followed by manufacturing delays (21%) and discontinuations (11%), and other issues including an increase in demand created by another shortage, he said at the meeting.

As with older generic drugs, there's little financial incentive to produce older sterile injectables such as propofol, which sell for as little as 48 cents for a 20-mL vial. In such cases, manufacturing glitches can often convince companies to pull the plug on a product, creating shortages.

Most hospitals aren't immune. A June 2011 survey of 820 nonfederal, short-term, acute care hospitals by the American Hospital Association found that almost 99% had experienced one or more drugs shortages in the first 6 months of 2011; 44% reported at least 21 shortages during that time. In addition, nearly half reported experiencing drug shortages on a daily basis, 40% on a weekly basis, and 13% on a monthly basis.

Almost all these hospitals (96%) had experienced shortages of anesthesia for surgery, followed by drugs used for emergency care (91%), cardiovascular care (90%), GI/nutrition (89%), pain management (88%), infectious disease (83%), and oncology (66%).

Drug shortages have hit the fields of oncology and anesthesiology particularly hard, often causing the delay or postponement of clinical trials of cancer treatments.

Shortages of propofol and succinylcholine have been common. Dr. Frederick Blum, past president of the American College of Emergency Physicians, who practices in Morgantown, W. Va., described being told there was no succinylcholine available when he recently requested it as he was about to intubate a trauma patient. When he asked for the next best drug, it wasn't available either because supply had been depleted from the succinylcholine shortage. A third, less-than-ideal alternative was found. But Dr. Blum said that after 30 years of practice, during which time he probably has used succinylcholine thousands of times, he left that shift shaking his head about the need to resort to using a third-choice drug.

Before the shortage of succinylcholine was resolved earlier this year, shortages of the agent also resulted in postponed surgeries at Veterans Administration Medical Centers.

Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society, noted that many generic cancer drugs are in short supply. Such drugs, developed years ago, often are inexpensive and “remain mainstays of many currently available and effective cancer treatment programs,” he said.

Generic cancer drugs that are in short supply include fluorouracil (5-FU), paclitaxel, daunorubicin, cytarabine, bleomycin, and cisplatin.

In many cases, such shortages are causing patients to have to travel further to get the drugs they need. Alternatively, they are treated with second- and third-line therapies that are not necessarily as effective, Dr. Lichtenfeld said. Many adult and pediatric trials of cancer treatments have been suspended when supply of the active control drug is no longer available, he added, and ACS is regularly contacted by patients and families who are looking for medications in short supply.

Exacerbating a shortage situation is the emergence of gray markets that trigger hoarding, he said.

Dr. Laura Porter of the Colon Cancer Alliance said that there have been shortages of 5 of 22 drugs used to treat for colon cancer, including 5-FU and leucovorin. Of the five, four are generic drugs. Last year, there were eight manufacturers of irinotecan, another drug used to treat colon cancer; today, there are only two, and the FDA has asked another company to start manufacturing the colon cancer agent.

At St. Jude Children's Research Hospital, Memphis, 1-4 drug shortages were reported every month in 2009, but in 2011, an average of 22 shortages have been reported every month, peaking at 28 in July. Notable shortages over the past year have included every component of total parenteral nutrition (TPN) and multivitamin injections, with the latter resulting in a hospitalization of a patient who could not take oral multivitamins and developed neurotoxicity and a thiamine deficiency, said James Hoffman, Pharm. D., the hospital's medication outcomes and safety officer.

Shortages of chemotherapy drugs have increased over the past 2 years. At St. Jude, where 85% of the cancer patients are enrolled in clinical trials, enrollment in acute myeloid leukemia protocols were suspended because of a shortage of cytarabine and lymphoma protocols were modified because of the shortage of mechlorethamine (nitrogen mustard). He pointed out that with 10 drugs, about 90% of patients with childhood acute lymphoblastic leukemia, the most common childhood cancer, can be cured, but over the last decade, 8 of these 10 drugs have been temporarily unavailable.

Substitute drugs can often be more expensive and involve additional labor costs, adding up to an estimated $415 million annually, according to Bryant Mangum, vice president of pharmacy services at Premier Healthcare Alliance, a network of over 2,500 hospitals in the United States.

An analysis of 636 unsolicited sales offers from gray-market vendors conducted by Premier found that the average markup of a drug price was 650%. Almost half the drugs were marked up by at least 1,000%, more than 25% were marked up by at least 2,000% – and a drug used to treat hypertension that usually costs $25.90 was being offered at $1,200, “a staggering increase,” he said at the meeting.

The greatest markups were for drugs used to treat patients in the areas of critical care sedation and surgery, chemotherapy, emergency care, and anti-infective drugs, he said.

Currently, the FDA's approach to drug shortages involves encouraging companies that make a product that is in short supply to ramp up manufacturing. The FDA also works with firms to address problems behind the shortage, such as manufacturing or quality issues. In rare cases, the FDA allows a product from an unapproved source to be imported into the U.S. temporarily, which was the case in 2010 for propofol and in 2011 for foscarnet, norepinephrine, leucovorin, and capecitabine.

Manufacturers have been giving the agency earlier notification about the potential for supply issues, a strategy that the FDA claims has successfully headed off some shortages. Such reports have helped prevent 99 shortages so far this year, an increase from 38 in 2010, Dr. Cox said at the meeting. Most of the prevented shortages (84) were derailed by expediting FDA review of new manufacturing sites, suppliers, and other issues that affected production of the drugs.

Other recommendations for resolving, preventing, and alleviating drug shortages now and in the future include creating stockpiles of certain drugs, similar to vaccine stockpiles; developing guidelines on treatment alternatives when there is a shortage of a drug, such as an antibiotic; and improving communications about drug shortages between FDA and stakeholders.

Clinicians need to be notified faster about shortages so they can be better prepared, according to several practicing physicians who spoke at the meeting. Of the hospitals that were surveyed by the AHA, 70% responded that the available information on how to manage drug shortages was not adequate.

Sources for such information include the American Society of Health-System Pharmacists, the FDA drug shortage website, and direct communication with manufacturers.

Dr. Blum, Dr. Cox, and Mr. Mangum had no disclosures. Dr. Lichtenfeld disclosed that he owns Johnson & Johnson stock and that the ACS receives grants from pharmaceutical companies and the foundations they oversee. Disclosure statements for Mr. Hoffman and Dr. Porter were not available.

FDA information on drug shortages, including current and resolved shortages, is available at www.fda.gov/drugs/drugsafety/drugshortages/default.htmdrugshortages@fda.hhs.govwww.fda.gov/Drugs/DrugSafety/DrugShortages/ucm142398.htmCBERshortages@fda.hhs.gov

To see a video about drug shortages and an interview with Michael R. Cohen, president of the Institute for Safe Medication Practices, scan the QR code below.

Source Elsevier Global Medical News

SILVER SPRING, MD. – With their increasing prevalence, drug shortages in the United States have led to delays in treatment, forced the use of less effective alternatives, and encouraged a burgeoning gray market that sells tough-to-obtain medications at highly inflated prices, according to stakeholders gathered at a recent FDA meeting.

Shortfalls in drug supply have increased in the United States, with 178 shortages of products reported in 2010, up from 61 in 2005, according to Dr. Edward Cox, coordinator of the FDA's drug shortage program. Disproportionately affected are generic drugs and sterile injectable products; the latter accounted for two-thirds of the shortages last year.

About half of the injectable shortages were caused by problems with product quality, followed by manufacturing delays (21%) and discontinuations (11%), and other issues including an increase in demand created by another shortage, he said at the meeting.

As with older generic drugs, there's little financial incentive to produce older sterile injectables such as propofol, which sell for as little as 48 cents for a 20-mL vial. In such cases, manufacturing glitches can often convince companies to pull the plug on a product, creating shortages.

Most hospitals aren't immune. A June 2011 survey of 820 nonfederal, short-term, acute care hospitals by the American Hospital Association found that almost 99% had experienced one or more drugs shortages in the first 6 months of 2011; 44% reported at least 21 shortages during that time. In addition, nearly half reported experiencing drug shortages on a daily basis, 40% on a weekly basis, and 13% on a monthly basis.

Almost all these hospitals (96%) had experienced shortages of anesthesia for surgery, followed by drugs used for emergency care (91%), cardiovascular care (90%), GI/nutrition (89%), pain management (88%), infectious disease (83%), and oncology (66%).

Drug shortages have hit the fields of oncology and anesthesiology particularly hard, often causing the delay or postponement of clinical trials of cancer treatments.

Shortages of propofol and succinylcholine have been common. Dr. Frederick Blum, past president of the American College of Emergency Physicians, who practices in Morgantown, W. Va., described being told there was no succinylcholine available when he recently requested it as he was about to intubate a trauma patient. When he asked for the next best drug, it wasn't available either because supply had been depleted from the succinylcholine shortage. A third, less-than-ideal alternative was found. But Dr. Blum said that after 30 years of practice, during which time he probably has used succinylcholine thousands of times, he left that shift shaking his head about the need to resort to using a third-choice drug.

Before the shortage of succinylcholine was resolved earlier this year, shortages of the agent also resulted in postponed surgeries at Veterans Administration Medical Centers.

Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society, noted that many generic cancer drugs are in short supply. Such drugs, developed years ago, often are inexpensive and “remain mainstays of many currently available and effective cancer treatment programs,” he said.

Generic cancer drugs that are in short supply include fluorouracil (5-FU), paclitaxel, daunorubicin, cytarabine, bleomycin, and cisplatin.

In many cases, such shortages are causing patients to have to travel further to get the drugs they need. Alternatively, they are treated with second- and third-line therapies that are not necessarily as effective, Dr. Lichtenfeld said. Many adult and pediatric trials of cancer treatments have been suspended when supply of the active control drug is no longer available, he added, and ACS is regularly contacted by patients and families who are looking for medications in short supply.

Exacerbating a shortage situation is the emergence of gray markets that trigger hoarding, he said.

Dr. Laura Porter of the Colon Cancer Alliance said that there have been shortages of 5 of 22 drugs used to treat for colon cancer, including 5-FU and leucovorin. Of the five, four are generic drugs. Last year, there were eight manufacturers of irinotecan, another drug used to treat colon cancer; today, there are only two, and the FDA has asked another company to start manufacturing the colon cancer agent.

At St. Jude Children's Research Hospital, Memphis, 1-4 drug shortages were reported every month in 2009, but in 2011, an average of 22 shortages have been reported every month, peaking at 28 in July. Notable shortages over the past year have included every component of total parenteral nutrition (TPN) and multivitamin injections, with the latter resulting in a hospitalization of a patient who could not take oral multivitamins and developed neurotoxicity and a thiamine deficiency, said James Hoffman, Pharm. D., the hospital's medication outcomes and safety officer.

Shortages of chemotherapy drugs have increased over the past 2 years. At St. Jude, where 85% of the cancer patients are enrolled in clinical trials, enrollment in acute myeloid leukemia protocols were suspended because of a shortage of cytarabine and lymphoma protocols were modified because of the shortage of mechlorethamine (nitrogen mustard). He pointed out that with 10 drugs, about 90% of patients with childhood acute lymphoblastic leukemia, the most common childhood cancer, can be cured, but over the last decade, 8 of these 10 drugs have been temporarily unavailable.

Substitute drugs can often be more expensive and involve additional labor costs, adding up to an estimated $415 million annually, according to Bryant Mangum, vice president of pharmacy services at Premier Healthcare Alliance, a network of over 2,500 hospitals in the United States.

An analysis of 636 unsolicited sales offers from gray-market vendors conducted by Premier found that the average markup of a drug price was 650%. Almost half the drugs were marked up by at least 1,000%, more than 25% were marked up by at least 2,000% – and a drug used to treat hypertension that usually costs $25.90 was being offered at $1,200, “a staggering increase,” he said at the meeting.

The greatest markups were for drugs used to treat patients in the areas of critical care sedation and surgery, chemotherapy, emergency care, and anti-infective drugs, he said.

Currently, the FDA's approach to drug shortages involves encouraging companies that make a product that is in short supply to ramp up manufacturing. The FDA also works with firms to address problems behind the shortage, such as manufacturing or quality issues. In rare cases, the FDA allows a product from an unapproved source to be imported into the U.S. temporarily, which was the case in 2010 for propofol and in 2011 for foscarnet, norepinephrine, leucovorin, and capecitabine.

Manufacturers have been giving the agency earlier notification about the potential for supply issues, a strategy that the FDA claims has successfully headed off some shortages. Such reports have helped prevent 99 shortages so far this year, an increase from 38 in 2010, Dr. Cox said at the meeting. Most of the prevented shortages (84) were derailed by expediting FDA review of new manufacturing sites, suppliers, and other issues that affected production of the drugs.

Other recommendations for resolving, preventing, and alleviating drug shortages now and in the future include creating stockpiles of certain drugs, similar to vaccine stockpiles; developing guidelines on treatment alternatives when there is a shortage of a drug, such as an antibiotic; and improving communications about drug shortages between FDA and stakeholders.

Clinicians need to be notified faster about shortages so they can be better prepared, according to several practicing physicians who spoke at the meeting. Of the hospitals that were surveyed by the AHA, 70% responded that the available information on how to manage drug shortages was not adequate.

Sources for such information include the American Society of Health-System Pharmacists, the FDA drug shortage website, and direct communication with manufacturers.

Dr. Blum, Dr. Cox, and Mr. Mangum had no disclosures. Dr. Lichtenfeld disclosed that he owns Johnson & Johnson stock and that the ACS receives grants from pharmaceutical companies and the foundations they oversee. Disclosure statements for Mr. Hoffman and Dr. Porter were not available.

FDA information on drug shortages, including current and resolved shortages, is available at www.fda.gov/drugs/drugsafety/drugshortages/default.htmdrugshortages@fda.hhs.govwww.fda.gov/Drugs/DrugSafety/DrugShortages/ucm142398.htmCBERshortages@fda.hhs.gov

To see a video about drug shortages and an interview with Michael R. Cohen, president of the Institute for Safe Medication Practices, scan the QR code below.

Source Elsevier Global Medical News

SILVER SPRING, MD. – With their increasing prevalence, drug shortages in the United States have led to delays in treatment, forced the use of less effective alternatives, and encouraged a burgeoning gray market that sells tough-to-obtain medications at highly inflated prices, according to stakeholders gathered at a recent FDA meeting.

Shortfalls in drug supply have increased in the United States, with 178 shortages of products reported in 2010, up from 61 in 2005, according to Dr. Edward Cox, coordinator of the FDA's drug shortage program. Disproportionately affected are generic drugs and sterile injectable products; the latter accounted for two-thirds of the shortages last year.

About half of the injectable shortages were caused by problems with product quality, followed by manufacturing delays (21%) and discontinuations (11%), and other issues including an increase in demand created by another shortage, he said at the meeting.

As with older generic drugs, there's little financial incentive to produce older sterile injectables such as propofol, which sell for as little as 48 cents for a 20-mL vial. In such cases, manufacturing glitches can often convince companies to pull the plug on a product, creating shortages.

Most hospitals aren't immune. A June 2011 survey of 820 nonfederal, short-term, acute care hospitals by the American Hospital Association found that almost 99% had experienced one or more drugs shortages in the first 6 months of 2011; 44% reported at least 21 shortages during that time. In addition, nearly half reported experiencing drug shortages on a daily basis, 40% on a weekly basis, and 13% on a monthly basis.

Almost all these hospitals (96%) had experienced shortages of anesthesia for surgery, followed by drugs used for emergency care (91%), cardiovascular care (90%), GI/nutrition (89%), pain management (88%), infectious disease (83%), and oncology (66%).

Drug shortages have hit the fields of oncology and anesthesiology particularly hard, often causing the delay or postponement of clinical trials of cancer treatments.

Shortages of propofol and succinylcholine have been common. Dr. Frederick Blum, past president of the American College of Emergency Physicians, who practices in Morgantown, W. Va., described being told there was no succinylcholine available when he recently requested it as he was about to intubate a trauma patient. When he asked for the next best drug, it wasn't available either because supply had been depleted from the succinylcholine shortage. A third, less-than-ideal alternative was found. But Dr. Blum said that after 30 years of practice, during which time he probably has used succinylcholine thousands of times, he left that shift shaking his head about the need to resort to using a third-choice drug.

Before the shortage of succinylcholine was resolved earlier this year, shortages of the agent also resulted in postponed surgeries at Veterans Administration Medical Centers.

Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society, noted that many generic cancer drugs are in short supply. Such drugs, developed years ago, often are inexpensive and “remain mainstays of many currently available and effective cancer treatment programs,” he said.

Generic cancer drugs that are in short supply include fluorouracil (5-FU), paclitaxel, daunorubicin, cytarabine, bleomycin, and cisplatin.

In many cases, such shortages are causing patients to have to travel further to get the drugs they need. Alternatively, they are treated with second- and third-line therapies that are not necessarily as effective, Dr. Lichtenfeld said. Many adult and pediatric trials of cancer treatments have been suspended when supply of the active control drug is no longer available, he added, and ACS is regularly contacted by patients and families who are looking for medications in short supply.

Exacerbating a shortage situation is the emergence of gray markets that trigger hoarding, he said.

Dr. Laura Porter of the Colon Cancer Alliance said that there have been shortages of 5 of 22 drugs used to treat for colon cancer, including 5-FU and leucovorin. Of the five, four are generic drugs. Last year, there were eight manufacturers of irinotecan, another drug used to treat colon cancer; today, there are only two, and the FDA has asked another company to start manufacturing the colon cancer agent.

At St. Jude Children's Research Hospital, Memphis, 1-4 drug shortages were reported every month in 2009, but in 2011, an average of 22 shortages have been reported every month, peaking at 28 in July. Notable shortages over the past year have included every component of total parenteral nutrition (TPN) and multivitamin injections, with the latter resulting in a hospitalization of a patient who could not take oral multivitamins and developed neurotoxicity and a thiamine deficiency, said James Hoffman, Pharm. D., the hospital's medication outcomes and safety officer.

Shortages of chemotherapy drugs have increased over the past 2 years. At St. Jude, where 85% of the cancer patients are enrolled in clinical trials, enrollment in acute myeloid leukemia protocols were suspended because of a shortage of cytarabine and lymphoma protocols were modified because of the shortage of mechlorethamine (nitrogen mustard). He pointed out that with 10 drugs, about 90% of patients with childhood acute lymphoblastic leukemia, the most common childhood cancer, can be cured, but over the last decade, 8 of these 10 drugs have been temporarily unavailable.

Substitute drugs can often be more expensive and involve additional labor costs, adding up to an estimated $415 million annually, according to Bryant Mangum, vice president of pharmacy services at Premier Healthcare Alliance, a network of over 2,500 hospitals in the United States.

An analysis of 636 unsolicited sales offers from gray-market vendors conducted by Premier found that the average markup of a drug price was 650%. Almost half the drugs were marked up by at least 1,000%, more than 25% were marked up by at least 2,000% – and a drug used to treat hypertension that usually costs $25.90 was being offered at $1,200, “a staggering increase,” he said at the meeting.

The greatest markups were for drugs used to treat patients in the areas of critical care sedation and surgery, chemotherapy, emergency care, and anti-infective drugs, he said.

Currently, the FDA's approach to drug shortages involves encouraging companies that make a product that is in short supply to ramp up manufacturing. The FDA also works with firms to address problems behind the shortage, such as manufacturing or quality issues. In rare cases, the FDA allows a product from an unapproved source to be imported into the U.S. temporarily, which was the case in 2010 for propofol and in 2011 for foscarnet, norepinephrine, leucovorin, and capecitabine.

Manufacturers have been giving the agency earlier notification about the potential for supply issues, a strategy that the FDA claims has successfully headed off some shortages. Such reports have helped prevent 99 shortages so far this year, an increase from 38 in 2010, Dr. Cox said at the meeting. Most of the prevented shortages (84) were derailed by expediting FDA review of new manufacturing sites, suppliers, and other issues that affected production of the drugs.

Other recommendations for resolving, preventing, and alleviating drug shortages now and in the future include creating stockpiles of certain drugs, similar to vaccine stockpiles; developing guidelines on treatment alternatives when there is a shortage of a drug, such as an antibiotic; and improving communications about drug shortages between FDA and stakeholders.

Clinicians need to be notified faster about shortages so they can be better prepared, according to several practicing physicians who spoke at the meeting. Of the hospitals that were surveyed by the AHA, 70% responded that the available information on how to manage drug shortages was not adequate.

Sources for such information include the American Society of Health-System Pharmacists, the FDA drug shortage website, and direct communication with manufacturers.

Dr. Blum, Dr. Cox, and Mr. Mangum had no disclosures. Dr. Lichtenfeld disclosed that he owns Johnson & Johnson stock and that the ACS receives grants from pharmaceutical companies and the foundations they oversee. Disclosure statements for Mr. Hoffman and Dr. Porter were not available.

FDA information on drug shortages, including current and resolved shortages, is available at www.fda.gov/drugs/drugsafety/drugshortages/default.htmdrugshortages@fda.hhs.govwww.fda.gov/Drugs/DrugSafety/DrugShortages/ucm142398.htmCBERshortages@fda.hhs.gov

To see a video about drug shortages and an interview with Michael R. Cohen, president of the Institute for Safe Medication Practices, scan the QR code below.

Source Elsevier Global Medical News

SILVER SPRING, MD. – A Food and Drug Administration advisory panel unanimously agreed that there was not enough evidence to support approval of rasagiline for slowing the clinical progression of Parkinson's disease, although they believed the data were promising.

The FDA's Peripheral and Central Nervous System Drugs Advisory Committee voted 17-0 that the manufacturer of rasagiline had not provided substantial evidence that the drug was effective in delaying clinical progression of the disease in patients. Rasagiline was approved in 2006 in the United States for treating the signs and symptoms of Parkinson's disease, as initial monotherapy and as adjunct therapy to levodopa; it is marketed as Azilect by Teva Pharmaceuticals.

“The data are promising, they are just not compelling…it's crucial that there be compelling data for us to really move forward,” said Dr. Pooja Katri, one of the panelists and a neurologist at the University of Cincinnati.

Currently, no treatment is approved for slowing the clinical progression of Parkinson's disease.

Teva based its request for adding an indication for slowing clinical progression to the 1-mg dose of the monoamine oxidase B inhibitor on the results of two “delayed start” studies of patients with early Parkinson's: the ADAGIO (Attenuation of Disease Progression with Agilect/Azilect Once Daily) study, and the TEMPO (TVP-1012 in Early Monotherapy for PD Outpatient) study, which was part of the original approval application for rasagiline.

The ADAGIO study evaluated the drug's effects on clinical progression in about 1,100 patients with early, mild Parkinson's, who were not on other medications for the disease (N. Engl. J. Med. 2009;361:1268-78). The patients (mean age 62 years) were enrolled a mean of 138 days after diagnosis and were treated with 1 mg or 2 mg of rasagiline per day or placebo for 36 weeks, at which point those on placebo were switched to 1-mg or 2-mg doses. Progression of disease was measured with the Unified Parkinson's Disease Rating Scale (UPDRS).

At 72 weeks, the increase in mean UPDRS scores from baseline was smaller among patients who had been treated with the 1-mg dose from the start of the study than it was in those who had started the 1-mg dose at 36 weeks, indicating less disease progression in the former. The difference was statistically significant.

However, there was no difference in the UPDRS scores from baseline to the end of the study among those who had started the 2-mg dose at the start of the study and those who started the 2-mg dose at 36 weeks.

“This is the closest we have come to showing a drug slows clinical progression,” said Dr. C. Warren Olanow, the director of the Robert and John N. Bendheim Parkinson and Movement Disorder Center, Mount Sinai School of Medicine, New York. He spoke on behalf of Teva at the meeting.

In the TEMPO study, about 400 patients (mean age 61 years) in the United States and Canada, who had had PD for a mean of 12 years, were randomized to 1 mg, 2 mg, or placebo for 26 weeks, at which time those on placebo were switched to the 2-mg dose (the delayed start group). Clinical outcomes, as measured by the impact on UPDRS scale changes, was better among those who started treatment early: the difference was 1.8 among those on 1 mg (P value of 0.05) and with 2 mg, the difference was 2.3 (P value of 0.01). At 52 weeks, those on 2 mg from the beginning of the study showed less deterioration, based on UPDRS scores, than did those whose treatment was delayed.

Dr. Olanow, the lead investigator of ADAGIO, said that patients in TEMPO had higher baseline UPDRS scores than those in ADAGIO, and that a post hoc analysis of ADAGIO data found that the 2-mg dose was associated with benefits among the patients with the highest baseline UPDRS scores. “We speculate that the UPDRS floor effect might have masked our ability to detect a difference between early and delayed start groups with this higher dose in such a mild population of patients,” he added, noting that the concept of a floor effect is “well-known” in Parkinson's disease and has been observed in previous trials where more prominent treatment effects have been observed in patients with higher UPDRS scores at baseline.

The failure of the 2-mg dose in the ADAGIO study was “the most troubling issue” with the data and there was “no robust finding for either dose,” said Tristan Massie, Ph.D., an FDA statistician who presented the agency's statistical analysis of the data at the meeting. The absence of an effect in the 2-mg group “raised questions about the biological plausibility of the 1 mg,” he added.

The panel agreed, cited other issues with the data, and voted unanimously that the study did not provide compelling evidence that the 1-mg, once-daily dose was effective. While they agreed that there was an unmet need for a treatment that slowed progression and that the data were promising and showed a signal for a disease-modifying effect, they said the evidence did not meet the high bar that should be set for proving such an effect, considering the enormous public health implications of a neuroprotection claim for a Parkinson's disease treatment.

The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.

In addition to Teva, the companies on Dr. Olanow's conflict of interest disclosure statement included Ceregene, Novartis, Lundbeck, and Merck Serono.

SILVER SPRING, MD. – A Food and Drug Administration advisory panel unanimously agreed that there was not enough evidence to support approval of rasagiline for slowing the clinical progression of Parkinson's disease, although they believed the data were promising.

The FDA's Peripheral and Central Nervous System Drugs Advisory Committee voted 17-0 that the manufacturer of rasagiline had not provided substantial evidence that the drug was effective in delaying clinical progression of the disease in patients. Rasagiline was approved in 2006 in the United States for treating the signs and symptoms of Parkinson's disease, as initial monotherapy and as adjunct therapy to levodopa; it is marketed as Azilect by Teva Pharmaceuticals.

“The data are promising, they are just not compelling…it's crucial that there be compelling data for us to really move forward,” said Dr. Pooja Katri, one of the panelists and a neurologist at the University of Cincinnati.

Currently, no treatment is approved for slowing the clinical progression of Parkinson's disease.

Teva based its request for adding an indication for slowing clinical progression to the 1-mg dose of the monoamine oxidase B inhibitor on the results of two “delayed start” studies of patients with early Parkinson's: the ADAGIO (Attenuation of Disease Progression with Agilect/Azilect Once Daily) study, and the TEMPO (TVP-1012 in Early Monotherapy for PD Outpatient) study, which was part of the original approval application for rasagiline.

The ADAGIO study evaluated the drug's effects on clinical progression in about 1,100 patients with early, mild Parkinson's, who were not on other medications for the disease (N. Engl. J. Med. 2009;361:1268-78). The patients (mean age 62 years) were enrolled a mean of 138 days after diagnosis and were treated with 1 mg or 2 mg of rasagiline per day or placebo for 36 weeks, at which point those on placebo were switched to 1-mg or 2-mg doses. Progression of disease was measured with the Unified Parkinson's Disease Rating Scale (UPDRS).

At 72 weeks, the increase in mean UPDRS scores from baseline was smaller among patients who had been treated with the 1-mg dose from the start of the study than it was in those who had started the 1-mg dose at 36 weeks, indicating less disease progression in the former. The difference was statistically significant.

However, there was no difference in the UPDRS scores from baseline to the end of the study among those who had started the 2-mg dose at the start of the study and those who started the 2-mg dose at 36 weeks.

“This is the closest we have come to showing a drug slows clinical progression,” said Dr. C. Warren Olanow, the director of the Robert and John N. Bendheim Parkinson and Movement Disorder Center, Mount Sinai School of Medicine, New York. He spoke on behalf of Teva at the meeting.

In the TEMPO study, about 400 patients (mean age 61 years) in the United States and Canada, who had had PD for a mean of 12 years, were randomized to 1 mg, 2 mg, or placebo for 26 weeks, at which time those on placebo were switched to the 2-mg dose (the delayed start group). Clinical outcomes, as measured by the impact on UPDRS scale changes, was better among those who started treatment early: the difference was 1.8 among those on 1 mg (P value of 0.05) and with 2 mg, the difference was 2.3 (P value of 0.01). At 52 weeks, those on 2 mg from the beginning of the study showed less deterioration, based on UPDRS scores, than did those whose treatment was delayed.

Dr. Olanow, the lead investigator of ADAGIO, said that patients in TEMPO had higher baseline UPDRS scores than those in ADAGIO, and that a post hoc analysis of ADAGIO data found that the 2-mg dose was associated with benefits among the patients with the highest baseline UPDRS scores. “We speculate that the UPDRS floor effect might have masked our ability to detect a difference between early and delayed start groups with this higher dose in such a mild population of patients,” he added, noting that the concept of a floor effect is “well-known” in Parkinson's disease and has been observed in previous trials where more prominent treatment effects have been observed in patients with higher UPDRS scores at baseline.

The failure of the 2-mg dose in the ADAGIO study was “the most troubling issue” with the data and there was “no robust finding for either dose,” said Tristan Massie, Ph.D., an FDA statistician who presented the agency's statistical analysis of the data at the meeting. The absence of an effect in the 2-mg group “raised questions about the biological plausibility of the 1 mg,” he added.

The panel agreed, cited other issues with the data, and voted unanimously that the study did not provide compelling evidence that the 1-mg, once-daily dose was effective. While they agreed that there was an unmet need for a treatment that slowed progression and that the data were promising and showed a signal for a disease-modifying effect, they said the evidence did not meet the high bar that should be set for proving such an effect, considering the enormous public health implications of a neuroprotection claim for a Parkinson's disease treatment.

The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.

In addition to Teva, the companies on Dr. Olanow's conflict of interest disclosure statement included Ceregene, Novartis, Lundbeck, and Merck Serono.

SILVER SPRING, MD. – A Food and Drug Administration advisory panel unanimously agreed that there was not enough evidence to support approval of rasagiline for slowing the clinical progression of Parkinson's disease, although they believed the data were promising.

The FDA's Peripheral and Central Nervous System Drugs Advisory Committee voted 17-0 that the manufacturer of rasagiline had not provided substantial evidence that the drug was effective in delaying clinical progression of the disease in patients. Rasagiline was approved in 2006 in the United States for treating the signs and symptoms of Parkinson's disease, as initial monotherapy and as adjunct therapy to levodopa; it is marketed as Azilect by Teva Pharmaceuticals.

“The data are promising, they are just not compelling…it's crucial that there be compelling data for us to really move forward,” said Dr. Pooja Katri, one of the panelists and a neurologist at the University of Cincinnati.

Currently, no treatment is approved for slowing the clinical progression of Parkinson's disease.

Teva based its request for adding an indication for slowing clinical progression to the 1-mg dose of the monoamine oxidase B inhibitor on the results of two “delayed start” studies of patients with early Parkinson's: the ADAGIO (Attenuation of Disease Progression with Agilect/Azilect Once Daily) study, and the TEMPO (TVP-1012 in Early Monotherapy for PD Outpatient) study, which was part of the original approval application for rasagiline.

The ADAGIO study evaluated the drug's effects on clinical progression in about 1,100 patients with early, mild Parkinson's, who were not on other medications for the disease (N. Engl. J. Med. 2009;361:1268-78). The patients (mean age 62 years) were enrolled a mean of 138 days after diagnosis and were treated with 1 mg or 2 mg of rasagiline per day or placebo for 36 weeks, at which point those on placebo were switched to 1-mg or 2-mg doses. Progression of disease was measured with the Unified Parkinson's Disease Rating Scale (UPDRS).

At 72 weeks, the increase in mean UPDRS scores from baseline was smaller among patients who had been treated with the 1-mg dose from the start of the study than it was in those who had started the 1-mg dose at 36 weeks, indicating less disease progression in the former. The difference was statistically significant.

However, there was no difference in the UPDRS scores from baseline to the end of the study among those who had started the 2-mg dose at the start of the study and those who started the 2-mg dose at 36 weeks.

“This is the closest we have come to showing a drug slows clinical progression,” said Dr. C. Warren Olanow, the director of the Robert and John N. Bendheim Parkinson and Movement Disorder Center, Mount Sinai School of Medicine, New York. He spoke on behalf of Teva at the meeting.

In the TEMPO study, about 400 patients (mean age 61 years) in the United States and Canada, who had had PD for a mean of 12 years, were randomized to 1 mg, 2 mg, or placebo for 26 weeks, at which time those on placebo were switched to the 2-mg dose (the delayed start group). Clinical outcomes, as measured by the impact on UPDRS scale changes, was better among those who started treatment early: the difference was 1.8 among those on 1 mg (P value of 0.05) and with 2 mg, the difference was 2.3 (P value of 0.01). At 52 weeks, those on 2 mg from the beginning of the study showed less deterioration, based on UPDRS scores, than did those whose treatment was delayed.

Dr. Olanow, the lead investigator of ADAGIO, said that patients in TEMPO had higher baseline UPDRS scores than those in ADAGIO, and that a post hoc analysis of ADAGIO data found that the 2-mg dose was associated with benefits among the patients with the highest baseline UPDRS scores. “We speculate that the UPDRS floor effect might have masked our ability to detect a difference between early and delayed start groups with this higher dose in such a mild population of patients,” he added, noting that the concept of a floor effect is “well-known” in Parkinson's disease and has been observed in previous trials where more prominent treatment effects have been observed in patients with higher UPDRS scores at baseline.

The failure of the 2-mg dose in the ADAGIO study was “the most troubling issue” with the data and there was “no robust finding for either dose,” said Tristan Massie, Ph.D., an FDA statistician who presented the agency's statistical analysis of the data at the meeting. The absence of an effect in the 2-mg group “raised questions about the biological plausibility of the 1 mg,” he added.

The panel agreed, cited other issues with the data, and voted unanimously that the study did not provide compelling evidence that the 1-mg, once-daily dose was effective. While they agreed that there was an unmet need for a treatment that slowed progression and that the data were promising and showed a signal for a disease-modifying effect, they said the evidence did not meet the high bar that should be set for proving such an effect, considering the enormous public health implications of a neuroprotection claim for a Parkinson's disease treatment.

The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.

In addition to Teva, the companies on Dr. Olanow's conflict of interest disclosure statement included Ceregene, Novartis, Lundbeck, and Merck Serono.

The failure of Xigris to show an effect on mortality in a clinical trial of patients with septic shock has prompted the manufacturer to withdraw the drug from the United States and other countries where it is approved, Eli Lilly & Co. announced on Oct. 25.

Xigris (drotrecogin alfa [activated]), a recombinant form of human activated protein C, was approved in the United States in 2001 for the reduction in mortality in adults with severe sepsis who have a high risk of death. It was approved in 2002 in the European Union for the treatment of adults with severe sepsis and multiple organ failure "when added to best standard care."

The PROWESS-SHOCK study, conducted as a condition for continued approval in Europe, showed that treatment with Xigris did not meet the primary end point, a significant reduction in 28 day all-cause mortality in patients with septic shock, Lilly announced in a statement.

"While there were no new safety findings, the study failed to demonstrate that Xigris improved patient survival and thus calls into question the benefit-risk profile of Xigris and its continued use," Dr. Timothy Garnett, senior vice president and chief medical officer at Lilly, said in the statement. Xigris should be stopped in patients currently being treated with it, and the drug should not be started in new patients, he added.

More details of the study were provided in a statement released by the Food and Drug Administration on the withdrawal, which said that the preliminary analyses of the data found that the 28-day all-cause mortality rate was 26.4% (223/846) among Xigris-treated patients, compared with 24.2% (202/834) among those on placebo, which was not a statistically significant difference.

In 2009, the FDA issued a statement about an ongoing safety review of Xigris, regarding the increased risk of serious bleeding events and deaths in a study of patients treated with Xigris who also had risk factors for bleeding at baseline. The increased risk of bleeding associated with Xigris treatment was a significant safety issue associated with the drug, which was contraindicated in patients with active internal bleeding and other situations in which bleeding could result in significant morbidity or death.

For questions about Xigris, the company can be contacted at 800-LillyRx or www.Lilly.com.

The failure of Xigris to show an effect on mortality in a clinical trial of patients with septic shock has prompted the manufacturer to withdraw the drug from the United States and other countries where it is approved, Eli Lilly & Co. announced on Oct. 25.

Xigris (drotrecogin alfa [activated]), a recombinant form of human activated protein C, was approved in the United States in 2001 for the reduction in mortality in adults with severe sepsis who have a high risk of death. It was approved in 2002 in the European Union for the treatment of adults with severe sepsis and multiple organ failure "when added to best standard care."

The PROWESS-SHOCK study, conducted as a condition for continued approval in Europe, showed that treatment with Xigris did not meet the primary end point, a significant reduction in 28 day all-cause mortality in patients with septic shock, Lilly announced in a statement.

"While there were no new safety findings, the study failed to demonstrate that Xigris improved patient survival and thus calls into question the benefit-risk profile of Xigris and its continued use," Dr. Timothy Garnett, senior vice president and chief medical officer at Lilly, said in the statement. Xigris should be stopped in patients currently being treated with it, and the drug should not be started in new patients, he added.

More details of the study were provided in a statement released by the Food and Drug Administration on the withdrawal, which said that the preliminary analyses of the data found that the 28-day all-cause mortality rate was 26.4% (223/846) among Xigris-treated patients, compared with 24.2% (202/834) among those on placebo, which was not a statistically significant difference.

In 2009, the FDA issued a statement about an ongoing safety review of Xigris, regarding the increased risk of serious bleeding events and deaths in a study of patients treated with Xigris who also had risk factors for bleeding at baseline. The increased risk of bleeding associated with Xigris treatment was a significant safety issue associated with the drug, which was contraindicated in patients with active internal bleeding and other situations in which bleeding could result in significant morbidity or death.

For questions about Xigris, the company can be contacted at 800-LillyRx or www.Lilly.com.

The failure of Xigris to show an effect on mortality in a clinical trial of patients with septic shock has prompted the manufacturer to withdraw the drug from the United States and other countries where it is approved, Eli Lilly & Co. announced on Oct. 25.

Xigris (drotrecogin alfa [activated]), a recombinant form of human activated protein C, was approved in the United States in 2001 for the reduction in mortality in adults with severe sepsis who have a high risk of death. It was approved in 2002 in the European Union for the treatment of adults with severe sepsis and multiple organ failure "when added to best standard care."

The PROWESS-SHOCK study, conducted as a condition for continued approval in Europe, showed that treatment with Xigris did not meet the primary end point, a significant reduction in 28 day all-cause mortality in patients with septic shock, Lilly announced in a statement.

"While there were no new safety findings, the study failed to demonstrate that Xigris improved patient survival and thus calls into question the benefit-risk profile of Xigris and its continued use," Dr. Timothy Garnett, senior vice president and chief medical officer at Lilly, said in the statement. Xigris should be stopped in patients currently being treated with it, and the drug should not be started in new patients, he added.

More details of the study were provided in a statement released by the Food and Drug Administration on the withdrawal, which said that the preliminary analyses of the data found that the 28-day all-cause mortality rate was 26.4% (223/846) among Xigris-treated patients, compared with 24.2% (202/834) among those on placebo, which was not a statistically significant difference.

In 2009, the FDA issued a statement about an ongoing safety review of Xigris, regarding the increased risk of serious bleeding events and deaths in a study of patients treated with Xigris who also had risk factors for bleeding at baseline. The increased risk of bleeding associated with Xigris treatment was a significant safety issue associated with the drug, which was contraindicated in patients with active internal bleeding and other situations in which bleeding could result in significant morbidity or death.

For questions about Xigris, the company can be contacted at 800-LillyRx or www.Lilly.com.

The risk of being hospitalized for neuropsychiatric events was similar among people treated with the smoking cessation drug varenicline and those treated with nicotine replacement therapy, the Food and Drug Administration announced Oct. 24.

The agency’s conclusions were based on two epidemiologic studies reviewed by the FDA as part of its ongoing safety review of varenicline.

However, the two retrospective cohort studies evaluated only neuropsychiatric events that resulted in hospitalizations and were not large enough to detect rare events associated with varenicline, a nicotine receptor agonist, marketed as Chantix by Pfizer, the statement said. And although the studies "did not suggest an increased risk of neuropsychiatric events that result in hospitalization, they do not rule out an increased risk of other neuropsychiatric events with Chantix."

Still, based on the assessment of currently available data, "the agency continues to believe that the drug’s benefits outweigh the risks and the current warnings in the Chantix drug label are appropriate," and health care professionals should continue to follow the recommendations in the drug’s label, the statement said.

The FDA also recommends that clinicians ask patients whether they have any history of psychiatric illness before starting varenicline treatment – and should tell them to immediately stop taking the drug and contact a health care professional "if agitation, hostility, depressed mood, or changes in behavior or thinking that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior while taking or shortly after discontinuing Chantix."

Pfizer is conducting a large clinical safety trial that is assessing neuropsychiatric events as outcomes, but the results are not expected until 2017.

Since varenicline was approved by the FDA in 2006, serious neuropsychiatric events – including changes in behavior, agitation, depressed mood and suicidal thoughts or actions – have been reported in patients during and after treatment, and are described in a boxed warning and in the warnings and precautions sections of the drug’s label. These reports also have been described in previous FDA advisories, including in 2008 and in 2009.

One of the two observational studies sponsored by the FDA was conducted by the Department of Veterans Affairs’ Center for Medication Safety. This retrospective study compared mental health hospitalizations among people who started treatment with varenicline or nicotine replacement therapy between May 2006 and September 2007. (About 14,000 people were in each group.)

The second study was conducted by the Department of Defense U.S. Army Medical Command’s Pharmacovigilance Center, which compared the rates of hospitalization for neuropsychiatric events for 20 days after starting treatment with either varenicline (almost 20,000 patients) or the nicotine replacement patch (almost 16,000 patients), who started treatment from Aug. 1, 2006, through Aug. 31, 2007.

Between May 2006 through July 2011, about 21.8 million prescriptions for varenicline were dispensed and about 8.9 million patients have received varenicline prescriptions through outpatient retail pharmacies in the United States, the statement said.

Serious adverse events related to varenicline should be reported to the FDA’s Medwatch program, or by calling 800-332-1088.

The risk of being hospitalized for neuropsychiatric events was similar among people treated with the smoking cessation drug varenicline and those treated with nicotine replacement therapy, the Food and Drug Administration announced Oct. 24.

The agency’s conclusions were based on two epidemiologic studies reviewed by the FDA as part of its ongoing safety review of varenicline.

However, the two retrospective cohort studies evaluated only neuropsychiatric events that resulted in hospitalizations and were not large enough to detect rare events associated with varenicline, a nicotine receptor agonist, marketed as Chantix by Pfizer, the statement said. And although the studies "did not suggest an increased risk of neuropsychiatric events that result in hospitalization, they do not rule out an increased risk of other neuropsychiatric events with Chantix."

Still, based on the assessment of currently available data, "the agency continues to believe that the drug’s benefits outweigh the risks and the current warnings in the Chantix drug label are appropriate," and health care professionals should continue to follow the recommendations in the drug’s label, the statement said.

The FDA also recommends that clinicians ask patients whether they have any history of psychiatric illness before starting varenicline treatment – and should tell them to immediately stop taking the drug and contact a health care professional "if agitation, hostility, depressed mood, or changes in behavior or thinking that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior while taking or shortly after discontinuing Chantix."

Pfizer is conducting a large clinical safety trial that is assessing neuropsychiatric events as outcomes, but the results are not expected until 2017.

Since varenicline was approved by the FDA in 2006, serious neuropsychiatric events – including changes in behavior, agitation, depressed mood and suicidal thoughts or actions – have been reported in patients during and after treatment, and are described in a boxed warning and in the warnings and precautions sections of the drug’s label. These reports also have been described in previous FDA advisories, including in 2008 and in 2009.

One of the two observational studies sponsored by the FDA was conducted by the Department of Veterans Affairs’ Center for Medication Safety. This retrospective study compared mental health hospitalizations among people who started treatment with varenicline or nicotine replacement therapy between May 2006 and September 2007. (About 14,000 people were in each group.)

The second study was conducted by the Department of Defense U.S. Army Medical Command’s Pharmacovigilance Center, which compared the rates of hospitalization for neuropsychiatric events for 20 days after starting treatment with either varenicline (almost 20,000 patients) or the nicotine replacement patch (almost 16,000 patients), who started treatment from Aug. 1, 2006, through Aug. 31, 2007.

Between May 2006 through July 2011, about 21.8 million prescriptions for varenicline were dispensed and about 8.9 million patients have received varenicline prescriptions through outpatient retail pharmacies in the United States, the statement said.

Serious adverse events related to varenicline should be reported to the FDA’s Medwatch program, or by calling 800-332-1088.

The risk of being hospitalized for neuropsychiatric events was similar among people treated with the smoking cessation drug varenicline and those treated with nicotine replacement therapy, the Food and Drug Administration announced Oct. 24.

The agency’s conclusions were based on two epidemiologic studies reviewed by the FDA as part of its ongoing safety review of varenicline.

However, the two retrospective cohort studies evaluated only neuropsychiatric events that resulted in hospitalizations and were not large enough to detect rare events associated with varenicline, a nicotine receptor agonist, marketed as Chantix by Pfizer, the statement said. And although the studies "did not suggest an increased risk of neuropsychiatric events that result in hospitalization, they do not rule out an increased risk of other neuropsychiatric events with Chantix."

Still, based on the assessment of currently available data, "the agency continues to believe that the drug’s benefits outweigh the risks and the current warnings in the Chantix drug label are appropriate," and health care professionals should continue to follow the recommendations in the drug’s label, the statement said.

The FDA also recommends that clinicians ask patients whether they have any history of psychiatric illness before starting varenicline treatment – and should tell them to immediately stop taking the drug and contact a health care professional "if agitation, hostility, depressed mood, or changes in behavior or thinking that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior while taking or shortly after discontinuing Chantix."

Pfizer is conducting a large clinical safety trial that is assessing neuropsychiatric events as outcomes, but the results are not expected until 2017.

Since varenicline was approved by the FDA in 2006, serious neuropsychiatric events – including changes in behavior, agitation, depressed mood and suicidal thoughts or actions – have been reported in patients during and after treatment, and are described in a boxed warning and in the warnings and precautions sections of the drug’s label. These reports also have been described in previous FDA advisories, including in 2008 and in 2009.

One of the two observational studies sponsored by the FDA was conducted by the Department of Veterans Affairs’ Center for Medication Safety. This retrospective study compared mental health hospitalizations among people who started treatment with varenicline or nicotine replacement therapy between May 2006 and September 2007. (About 14,000 people were in each group.)

The second study was conducted by the Department of Defense U.S. Army Medical Command’s Pharmacovigilance Center, which compared the rates of hospitalization for neuropsychiatric events for 20 days after starting treatment with either varenicline (almost 20,000 patients) or the nicotine replacement patch (almost 16,000 patients), who started treatment from Aug. 1, 2006, through Aug. 31, 2007.

Between May 2006 through July 2011, about 21.8 million prescriptions for varenicline were dispensed and about 8.9 million patients have received varenicline prescriptions through outpatient retail pharmacies in the United States, the statement said.

Serious adverse events related to varenicline should be reported to the FDA’s Medwatch program, or by calling 800-332-1088.

The first generic formulations of the atypical antipsychotic olanzapine have been approved by the Food and Drug Administration, the agency announced Oct. 24.

The new approvals are for olanzapine tablets and olanzapine orally disintegrating tablets.

Marketed as Zyprexa, olanzapine was first approved in 1996. It is indicated for the treatment of schizophrenia and bipolar I disorder. Like the trade version of the drug, generic olanzapine prescriptions must be dispensed with a medication guide for patients that describes the risks and adverse effects associate with the drug, which are also included in the drug’s label, the statement said.

A boxed warning on the label states that treatment with antipsychotic drugs increases the risk of death in elderly patients with dementia-related psychosis, and that olanzapine is not approved for treating patients with dementia-related psychosis, according to the FDA.

The FDA statement also refers to the serious risks associated with olanzapine, which include weight gain, hyperglycemia, and increased cholesterol and triglycerides. In addition, the statement says that "clinicians should take these effects into account when deciding to use this type of medication."

The manufacturers of generic olanzapine tablets are Dr. Reddy’s Laboratories and Teva Pharmaceuticals USA. The manufacturers of generic forms of olanzapine orally disintegrating tablets are Apotex, Dr. Reddy’s, and Par Pharmaceuticals, according to the FDA’s statement.

Olanzapine is the third atypical antipsychotic to become available in generic formulations. Clozapine was the first, followed by risperidone, according to an FDA spokesperson.

The first generic formulations of the atypical antipsychotic olanzapine have been approved by the Food and Drug Administration, the agency announced Oct. 24.

The new approvals are for olanzapine tablets and olanzapine orally disintegrating tablets.

Marketed as Zyprexa, olanzapine was first approved in 1996. It is indicated for the treatment of schizophrenia and bipolar I disorder. Like the trade version of the drug, generic olanzapine prescriptions must be dispensed with a medication guide for patients that describes the risks and adverse effects associate with the drug, which are also included in the drug’s label, the statement said.

A boxed warning on the label states that treatment with antipsychotic drugs increases the risk of death in elderly patients with dementia-related psychosis, and that olanzapine is not approved for treating patients with dementia-related psychosis, according to the FDA.

The FDA statement also refers to the serious risks associated with olanzapine, which include weight gain, hyperglycemia, and increased cholesterol and triglycerides. In addition, the statement says that "clinicians should take these effects into account when deciding to use this type of medication."

The manufacturers of generic olanzapine tablets are Dr. Reddy’s Laboratories and Teva Pharmaceuticals USA. The manufacturers of generic forms of olanzapine orally disintegrating tablets are Apotex, Dr. Reddy’s, and Par Pharmaceuticals, according to the FDA’s statement.

Olanzapine is the third atypical antipsychotic to become available in generic formulations. Clozapine was the first, followed by risperidone, according to an FDA spokesperson.

The first generic formulations of the atypical antipsychotic olanzapine have been approved by the Food and Drug Administration, the agency announced Oct. 24.

The new approvals are for olanzapine tablets and olanzapine orally disintegrating tablets.

Marketed as Zyprexa, olanzapine was first approved in 1996. It is indicated for the treatment of schizophrenia and bipolar I disorder. Like the trade version of the drug, generic olanzapine prescriptions must be dispensed with a medication guide for patients that describes the risks and adverse effects associate with the drug, which are also included in the drug’s label, the statement said.

A boxed warning on the label states that treatment with antipsychotic drugs increases the risk of death in elderly patients with dementia-related psychosis, and that olanzapine is not approved for treating patients with dementia-related psychosis, according to the FDA.

The FDA statement also refers to the serious risks associated with olanzapine, which include weight gain, hyperglycemia, and increased cholesterol and triglycerides. In addition, the statement says that "clinicians should take these effects into account when deciding to use this type of medication."

The manufacturers of generic olanzapine tablets are Dr. Reddy’s Laboratories and Teva Pharmaceuticals USA. The manufacturers of generic forms of olanzapine orally disintegrating tablets are Apotex, Dr. Reddy’s, and Par Pharmaceuticals, according to the FDA’s statement.

Olanzapine is the third atypical antipsychotic to become available in generic formulations. Clozapine was the first, followed by risperidone, according to an FDA spokesperson.

Gradually transferring diabetes care responsibilities from the parent to the teenager is among the recommendations for helping young people with diabetes make an effective, smooth transition from pediatric to adult care that are included in a position statement released by the American Diabetes Association.

But the bulk of prep work falls to pediatric health care providers, who should also start preparing teenagers and their families for this transition at least 1 year before they switch to an adult clinician, according to the statement "Diabetes Care for Emerging Adults."

The statement is a result of the ADA Transitions Working Group, which includes representatives of the American Academy of Pediatrics, American Association of Clinical Endocrinologists, Endocrine Society, Pediatric Endocrine Society, and other associations. The multidisciplinary group of experts and people with diabetes reviewed the issues related to the transition from pediatric to adult care that affect health care professionals as well as people with diabetes. The statement focuses on people aged 18-30 years, described as "emerging adults," and includes people with type 1 and type 2 diabetes.

This transition "represents a high-risk period for a person with diabetes, a perfect storm during which interruption of care is likely for multiple reasons," wrote the authors of the statement, Dr. Anne Peters of the University of Southern California, Los Angeles, and Dr. Lori Laffel of the Joslin Diabetes Center and Harvard University, Boston. "This is a critical time when patients not only assume responsibility for their diabetes self-care and interactions with the health care system but when they become more independent," and may move out of their parent’s home to go to college or start work, they wrote (Diabetes Care 2011;34:2477-85).

Tens of thousands of people in this age group with type 1 or type 2 diabetes are transitioning from pediatric to adult care every year in the United States, based on current estimates of young people with diabetes, according to the statement.

The statement points out that there are many challenges to making this transition, including gaps in health insurance coverage and gaps in health care professional training in how best to deliver care for this age group. More research is needed in this area, as well as in the training of providers who attend to the medical and psychosocial needs of young adults with diabetes.

Eight areas relevant to people in this age group are summarized in the statement. They are: differences between pediatric and adult diabetes care; poor glycemic control and other risk factors; loss to follow-up; increased risk of acute complications; psychosocial issues; sexual and reproductive health issues; alcohol, smoking, and drug abuse; and emergence of signs of chronic diabetes complications.

The statement points out that older teens and young adults are at a high risk for being disengaged from health care and, as a result, are at an increased risk for short-term complications such as hypoglycemia and long-term complications such as nephropathy and retinopathy. Interruptions in care explain some of the adverse outcomes in this age group, including an increased relative risk of death among young adults with diabetes, compared with those without diabetes. Fewer medical visits for diabetes, loss of parental supervision, and other factors such as increased alcohol consumption can also increase the risk of acute complications, they said.

Pediatric providers should give transitioning patients a written summary for them and their future adult health care provider that includes information on medications, past glycemic control, assessment of their diabetes self-care skills, and diabetes-related comorbidities, the statement said. Preparing patients for the transition should include individualized, developmentally appropriate care that gives the patient responsibilities in not only self-monitoring glucose but scheduling their own appointments. The transferring provider also should ensure that patients have a supply of medication, educate them about health insurance, evaluate and treat them for eating disorders, and provide mental health referrals.

"It is particularly important to create effective and translatable processes for the transition in care from pediatric to adult providers in order to optimize well-being and health for the near term," the authors concluded. Over the next decade, they expect to see "the emergence of evidence-based strategies that support best practice for the growing numbers of young adults with type 1 and type 2 diabetes who will be making this important transition."

The meeting of the writing group was supported with an unrestricted grant from the Jonas Brothers’ Change for the Children Foundation. Both Dr. Peters and Dr. Laffel disclosed ties to makers of diabetes drugs.

Gradually transferring diabetes care responsibilities from the parent to the teenager is among the recommendations for helping young people with diabetes make an effective, smooth transition from pediatric to adult care that are included in a position statement released by the American Diabetes Association.

But the bulk of prep work falls to pediatric health care providers, who should also start preparing teenagers and their families for this transition at least 1 year before they switch to an adult clinician, according to the statement "Diabetes Care for Emerging Adults."

The statement is a result of the ADA Transitions Working Group, which includes representatives of the American Academy of Pediatrics, American Association of Clinical Endocrinologists, Endocrine Society, Pediatric Endocrine Society, and other associations. The multidisciplinary group of experts and people with diabetes reviewed the issues related to the transition from pediatric to adult care that affect health care professionals as well as people with diabetes. The statement focuses on people aged 18-30 years, described as "emerging adults," and includes people with type 1 and type 2 diabetes.

This transition "represents a high-risk period for a person with diabetes, a perfect storm during which interruption of care is likely for multiple reasons," wrote the authors of the statement, Dr. Anne Peters of the University of Southern California, Los Angeles, and Dr. Lori Laffel of the Joslin Diabetes Center and Harvard University, Boston. "This is a critical time when patients not only assume responsibility for their diabetes self-care and interactions with the health care system but when they become more independent," and may move out of their parent’s home to go to college or start work, they wrote (Diabetes Care 2011;34:2477-85).

Tens of thousands of people in this age group with type 1 or type 2 diabetes are transitioning from pediatric to adult care every year in the United States, based on current estimates of young people with diabetes, according to the statement.

The statement points out that there are many challenges to making this transition, including gaps in health insurance coverage and gaps in health care professional training in how best to deliver care for this age group. More research is needed in this area, as well as in the training of providers who attend to the medical and psychosocial needs of young adults with diabetes.

Eight areas relevant to people in this age group are summarized in the statement. They are: differences between pediatric and adult diabetes care; poor glycemic control and other risk factors; loss to follow-up; increased risk of acute complications; psychosocial issues; sexual and reproductive health issues; alcohol, smoking, and drug abuse; and emergence of signs of chronic diabetes complications.

The statement points out that older teens and young adults are at a high risk for being disengaged from health care and, as a result, are at an increased risk for short-term complications such as hypoglycemia and long-term complications such as nephropathy and retinopathy. Interruptions in care explain some of the adverse outcomes in this age group, including an increased relative risk of death among young adults with diabetes, compared with those without diabetes. Fewer medical visits for diabetes, loss of parental supervision, and other factors such as increased alcohol consumption can also increase the risk of acute complications, they said.

Pediatric providers should give transitioning patients a written summary for them and their future adult health care provider that includes information on medications, past glycemic control, assessment of their diabetes self-care skills, and diabetes-related comorbidities, the statement said. Preparing patients for the transition should include individualized, developmentally appropriate care that gives the patient responsibilities in not only self-monitoring glucose but scheduling their own appointments. The transferring provider also should ensure that patients have a supply of medication, educate them about health insurance, evaluate and treat them for eating disorders, and provide mental health referrals.

"It is particularly important to create effective and translatable processes for the transition in care from pediatric to adult providers in order to optimize well-being and health for the near term," the authors concluded. Over the next decade, they expect to see "the emergence of evidence-based strategies that support best practice for the growing numbers of young adults with type 1 and type 2 diabetes who will be making this important transition."

The meeting of the writing group was supported with an unrestricted grant from the Jonas Brothers’ Change for the Children Foundation. Both Dr. Peters and Dr. Laffel disclosed ties to makers of diabetes drugs.

Gradually transferring diabetes care responsibilities from the parent to the teenager is among the recommendations for helping young people with diabetes make an effective, smooth transition from pediatric to adult care that are included in a position statement released by the American Diabetes Association.

But the bulk of prep work falls to pediatric health care providers, who should also start preparing teenagers and their families for this transition at least 1 year before they switch to an adult clinician, according to the statement "Diabetes Care for Emerging Adults."

The statement is a result of the ADA Transitions Working Group, which includes representatives of the American Academy of Pediatrics, American Association of Clinical Endocrinologists, Endocrine Society, Pediatric Endocrine Society, and other associations. The multidisciplinary group of experts and people with diabetes reviewed the issues related to the transition from pediatric to adult care that affect health care professionals as well as people with diabetes. The statement focuses on people aged 18-30 years, described as "emerging adults," and includes people with type 1 and type 2 diabetes.

This transition "represents a high-risk period for a person with diabetes, a perfect storm during which interruption of care is likely for multiple reasons," wrote the authors of the statement, Dr. Anne Peters of the University of Southern California, Los Angeles, and Dr. Lori Laffel of the Joslin Diabetes Center and Harvard University, Boston. "This is a critical time when patients not only assume responsibility for their diabetes self-care and interactions with the health care system but when they become more independent," and may move out of their parent’s home to go to college or start work, they wrote (Diabetes Care 2011;34:2477-85).

Tens of thousands of people in this age group with type 1 or type 2 diabetes are transitioning from pediatric to adult care every year in the United States, based on current estimates of young people with diabetes, according to the statement.

The statement points out that there are many challenges to making this transition, including gaps in health insurance coverage and gaps in health care professional training in how best to deliver care for this age group. More research is needed in this area, as well as in the training of providers who attend to the medical and psychosocial needs of young adults with diabetes.

Eight areas relevant to people in this age group are summarized in the statement. They are: differences between pediatric and adult diabetes care; poor glycemic control and other risk factors; loss to follow-up; increased risk of acute complications; psychosocial issues; sexual and reproductive health issues; alcohol, smoking, and drug abuse; and emergence of signs of chronic diabetes complications.

The statement points out that older teens and young adults are at a high risk for being disengaged from health care and, as a result, are at an increased risk for short-term complications such as hypoglycemia and long-term complications such as nephropathy and retinopathy. Interruptions in care explain some of the adverse outcomes in this age group, including an increased relative risk of death among young adults with diabetes, compared with those without diabetes. Fewer medical visits for diabetes, loss of parental supervision, and other factors such as increased alcohol consumption can also increase the risk of acute complications, they said.

Pediatric providers should give transitioning patients a written summary for them and their future adult health care provider that includes information on medications, past glycemic control, assessment of their diabetes self-care skills, and diabetes-related comorbidities, the statement said. Preparing patients for the transition should include individualized, developmentally appropriate care that gives the patient responsibilities in not only self-monitoring glucose but scheduling their own appointments. The transferring provider also should ensure that patients have a supply of medication, educate them about health insurance, evaluate and treat them for eating disorders, and provide mental health referrals.

"It is particularly important to create effective and translatable processes for the transition in care from pediatric to adult providers in order to optimize well-being and health for the near term," the authors concluded. Over the next decade, they expect to see "the emergence of evidence-based strategies that support best practice for the growing numbers of young adults with type 1 and type 2 diabetes who will be making this important transition."

The meeting of the writing group was supported with an unrestricted grant from the Jonas Brothers’ Change for the Children Foundation. Both Dr. Peters and Dr. Laffel disclosed ties to makers of diabetes drugs.