Patient Safety - News




Byetta and Patient Safety


2008-08-20 16:20:11

By: Richard Hellman, MD, FACP, FACE

The FDA has reported the receipt of six cases of hemorrhagic pancreatitis in patients taking the drug Byetta (exenatide). In all cases the Byetta was discontinued. Two of the patients died, and all six patients required hospitalization. The four survivors are currently reported to be improving. The FDA will be working with the manufacturer of the medication (Amylin Pharmacueticals) to strengthen the warnings on the label and make them more prominent. The FDA is recommending that if pancreatitis is suspected in a patient taking exenatide, the drug should be stopped immediately and not restarted.


This is not the first time there has been a FDA alert concerning exenatide. In October 2007 the FDA reported that it had received 30 reports of acute pancreatitis in patients taking exenatide for treatment of type 2 diabetes. The FDA reported at that time that none of the patients had died, and 27 of the 30 had other factors associated with pancreatitis. These factors included obesity, hypertriglyceridemia, and alcohol use. 21 of these patients were hospitalized, and five developed serious complications, such as dehydration and renal failure; suspected ileus; phlegmon; or ascites. Three of these patients developed symptoms of acute pancreatitis when the exenatide was restarted.


On May 1, 2008, the New England Journal of Medicine published a letter by Pablo Cure et al, entitled "Exenatide and Rare Adverse Events", a short letter by Drs. Ahmad and Swann from the FDA, which reviewed the previous FDA data on pancreatitis which was published in 2007, and a response from Amylin Pharmaceuticals. Dr Cure’s letter discussed the case of a patient who was discovered to have a gastric bezoar. The patient had had a prior islet cell transplantation and renal transplantation, and was placed on exenatide. The response by Amylin stated that only one additional spontaneously reported case of a bezoar in a patient receiving exenatide was known to them. They further stated that during the exenatide trials, no bezoars had been found in the study patients.



Patient Safety - News




CT Scans May Cause Medical Device Malfunctions


2008-07-18 08:07:35

By: Richard Hellman, MD, FACP, FACE

On July 15 , 2008, the FDA released a report stating that direct x-ray exposure from CT scanning has been reported to not only cause malfunction of cardiac pacemakers and defibrillators, but also to affect other devices, including neurostimulators and implanted or externally worn drug infusion pumps, including insulin pumps.


The FDA reported that the higher dose-rate capability of the newer x-ray machines, their increased use, and better reporting systems may all contribute to the findings. But it is far from clear as to how often insulin pumps, including both hospital infusion systems and the patient’s own external insulin pump, malfunction during CT scans.


In the case of pacemakers and implantable defibrillators, the most common effect of the prolonged exposure to the higher x-ray dose, often found with the newer CT scanners, including spiral CT's, is a over-sensing of the device. This can cause serious problems, including discharge of the defibrillator and pacemaker pauses. The neurostimulators have also been associated with unintended shocks. Although the report did not detail the effect on the insulin pumps, it is likely that the particular engineering of the pump and the dose of radiation may interact in a variety of ways, none that are desirable.


In the short term, we will monitor this carefully, but suggest that all clinicians be aware that, if possible, it may be best to have the insulin pump off during the CT scan. In any case, the insulin pump should be checked afterwards for malfunctioning if it is near the CT scanning device during the scan.




Patient Safety - News




AACE Calls For New Standards for Safer Insulin Pump Use


2008-05-24 15:56:18

By: Richard Hellman, MD, FACP, FACE

JACKSONVILLE, FL - "The American Association of Clinical Endocrinologists applauds the FDA's efforts to protect the safety of children and adolescents who are using insulin pumps," said Dr. Richard Hellman, the Association's President.


In the May edition of Pediatrics, Dr. Judith Cope, a physician at the FDA, provided new data that shows there is a serious problem regarding patient safety in insulin pump use. She reported data on 1594 injuries and 13 deaths in children and adolescents collected over 10 years. 82% of the cases resulted in hospitalization. The most common single issue was lack of education and, neither the patient nor the responsible adult knew enough about how the pump worked to avoid the injury or death that resulted. Although there were some cases due to mechanical malfunction of the pump, most problems were the result of human factors involved in the use of the pumps.


Unfortunately, the FDA has not yet provided similar data regarding the numbers of serious injuries in the larger group of pump users, adults who are using insulin pumps. This data, which is critically important, is very difficult to obtain and only the FDA is likely to have the ability to have access to the data of injuries and deaths from all of the manufacturers of insulin pumps.


There is every reason to be concerned that the data from insulin pump use in adults will also indicate a significant number of injuries and deaths similar to those found in the pediatric study. "The factors noted in the pediatric study that contributed to poor outcomes in children and adolescents can be expected to be present in a significant proportion of the adult population on insulin pumps," said Dr. Hellman.


Limited access to education at the time of initiation of pump therapy was a common problem in children and adolescents. It may be even more of a problem in adults. So is the lack of availability of support for pump use in emergencies. Many physicians and their staff who care for patients on insulin pumps are not sufficiently knowledgeable about the pump's performance to be able to troubleshoot when the patient makes a mistake or the pump malfunctions. Although telephone support is usually available from the manufacturer: the support personnel are neither the prescribers of the insulin doses nor directly involved in the patient's care.


In addition, as inadequate insurance coverage for adults becomes more common, new barriers to continuing care develop. Moreover, many new pumps are very sophisticated and complex, and their complexity can overwhelm even experienced users, and greatly increase the risk of error in patients who are inexperienced with pumps, or distracted, anxious, depressed, or having any transient cognitive problems as often occurs with either severely low or high blood glucose levels.


Dr. Hellman said that the American Association of Clinical Endocrinologists has an annual program, now in its third year, to teach and provide hands-on experience to all physicians completing specialized training in endocrinology. They are taught how to care for patients on insulin pumps, how to protect them from harm due to pump malfunction, and how to improve their patient's skills in using an insulin pump safely and well. The physicians find the program most valuable, but more such programs are needed. "This past year we appointed a task force of pump experts to develop guidelines and standards for initiating pump use and what we consider essential to provide for the safe and effective medical care of those on insulin pumps."


The American Association of Clinical Endocrinologists is very supportive of insulin pump technology and believes more patients can benefit from these pumps. But it is also clear that there are a significant number of patients who should not have been placed on these pumps. Dr. Hellman said, "These include patients with severe emotional problems that distract them from their safe self-care, as well as patients who cannot deal with the complexity of the pumps, suffer cognitive overload as a result, and do poorly. Most patients need more education and informed medical support, and nearly all do better in an integrated program that coordinates their diabetic care. But a continuing problem is that the education, both initial and continuing, and the medical support to deal with the specific problems and needs of pump users, is neither being provided nor paid for. As a result, we have a patient safety problem that may not be the pump itself, but a systems problem, that is, a failure of the system of care for pump support. The FDA needs to obtain the safety data on insulin pumps and share it with the scientific community as soon as possible. We need to move forward to make insulin pump use safer, and allow for the elimination of the deaths and injuries in pump use as those reported by Dr. Cope and the FDA team."






American Association of Clinical Endocrinologists

245 Riverside Avenue Suite 200

Jacksonville, FL 32202




Patient Safety - News




A First Step Toward Improving Drug Surveillance – The Sentinel Initiative


2008-05-24 15:54:33

By: Richard Hellman, MD, FACP, FACE

The Food & Drug Administration (FDA), in conjunction with the Department of Health & Human Service (HHS) and the Centers for Medicare & Medicaid Services (CMS), has just launched an effort, the Sentinel Initiative, to develop a post-market drug and device surveillance system that relies on electronic databases. In order to underscore the importance of this venture, the leadership of HHS, CMS, and FDA announced their plans at a joint press conference on Thursday, May 22, 2008. This followed the announcement of a CMS rule giving CMS (and the FDA) the authority to look at quality and safety concerns by querying the Part D Medicare prescription drug administrative database.


The beginning of the Sentinel Initiative is an important step, but alone, will not solve the problem regarding our woefully inadequate post-approval drug surveillance. A successful effort will take years of work and much more in the way of resources. But what the Sentinel Initiative does is potentially very important and we need to understand it.


The status quo has been that post-approval drug surveillance at the level of the FDA depended upon adverse event reporting that came from multiple sources, from device makers, pharmaceutical companies, and by physicians, nursing homes, and hospitals, to name just a few. The problem has always been the incompleteness of the data sent to the FDA. All too often, the report sent would have neither the correct diagnoses, nor the co-morbid conditions, nor other important and highly relevant clinical data. But this was better than the norm, which was no report at all. Hamstrung by too little data too late, it was not any surprise that the FDA was often caught flat-footed when a problem was uncovered. There simply has not been adequate data input to make valid conclusions, greatly delaying our finding the key signals of a problem regarding a particular drug or device.


It makes good sense to have a pilot project that is linking multiple electronic databases, both public and private, for the purpose of post-approval drug surveillance. We need to be able to identify the most destructive side-effects or hazards of a drug or device as soon as possible, not years afterwards. However, the Sentinel Initiative will fall short if the main databases queried are only administrative databases, which contain the diagnoses used for billing, but not the richness of the medical record, whose delineation of co-morbid conditions and more detailed diagnoses are essential for correct conclusions. These will not be available to the surveillance officers unless they have access to clinical electronic databases, and those are not the main electronic databases that are to be queried. Without accurate clinical data, ambiguity and false conclusions will be more likely.


On the other hand, the most serious adverse events probably will be captured by the administrative database, as for example, an unexpected hospitalization, a sudden cessation of the medication following a new major diagnosis, etc. This alone is important and a great improvement over the present status quo.


In the future, it is highly likely that we will emerge with a deeper understanding of the risk-benefit profile of each of the drugs and devices we use. This will help us to use them more safely. Our focus should be to provide the right drug for the right patient, rather than to vainly search for one drug that is right for everyone. A more sophisticated, data driven strategy for therapeutics may emerge, but only if this promising effort is continued and expanded, not stifled by inadequate funding or over-reliance on the more convenient, but less accurate clinical data found in administrative databases.


We all agree that our patients deserve the most accurate system for post-approval drug safety. If the Sentinel Inititative is developed to include high quality clinical databases, then high quality, timely drug safety surveillance may finally be within our reach.