“When I use a word, it means just what I choose it to mean…” – Humpty Dumpty

Even after all these years, I’m still surprised to learn new ways the words we use every day can mean different things to patients to whom we say them.

Take the word “biopsy.” To a dermatologist, it means “a test of a piece of tissue” (in our case, of skin), to help find out what the problem is.

I’ve always known that to many patients, the word “biopsy” suggests cancer, or at least the concern that there may be cancer, because cancer is the context in which most people hear the word: breast biopsy, prostate biopsy, and so on. It can therefore be useful to point out to patients when a biopsy is performed for diagnostic purposes and cancer is not even on the list of possibilities.

Lately, though, I’ve had a few encounters that highlighted other interesting ways the word “biopsy” can be misunderstood.

Case 1: Arnold the Irritated

“Arnold,” I say. “I need to biopsy this. Based on the results, it may need further treatment, but I doubt it.”

“I thought you were taking it off now,” says Arnold.

“No, I’m testing it, “I say.

“But I want it off,” says Arnold. “It gets irritated when I shave over it, so I want it off.”

“Yes,” I say, “but in order to remove it properly, I need to know what it is.”

“What?”

We have to go around a few more times before Arnold catches on.

Case 2: Gaetano the Outraged

“Gaetano is on the phone,” says my billing clerk. “He says you told him you weren’t going to biopsy his spot, and then he got a bill from the pathology lab.”

I call Gaetano. “You said you weren’t going to biopsy this,” he says. “You said you were sure you knew what it was, so you didn’t have to biopsy it.”

“First of all,” I explain, “I’m never totally sure. Your spot looked like a basal cell skin cancer, and that’s what it turned out to be. But I’ve had cases where the pathology results surprised me, and it turned out to be something less – or something more. So I have to check the biopsy.”

“I understand, Doctor” says Gaetano.

“In addition,” I go on, “what I actually meant to say was that I was not going to only take a biopsy of the spot. I was going to remove it completely, so that if my diagnosis was confirmed, you wouldn’t have to come back and have more done. Sorry if I didn’t make that clear.”

“So you biopsied it,” says Gaetano, but you didn’t just biopsy it. I get it. I think.”

Good for you, Gaetano. Next time I am going to – actually, next time I don’t know what I’ll do.

Case 3: Melvin the Clueless

“I understand your former dermatologist removed something from your arm,” I say to Melvin.

“Yes, they took a biopsy, and then they removed it,” says Melvin. “I just have one question.”

“What is that?” I ask.

“Which was the biopsy?” asks Melvin, “the first or the second?”

I didn’t let on, but inside I was shaking my head.

Even with the best will on both sides – and even if both are native speakers of the same language – there are just so many ways people can misunderstand each other. Humpty Dumpty was wrong. Words can mean what both the talker and the listener think they mean. Humpty Dumpty probably didn’t get out much.

Never biopsy an egg. 

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Skin & Allergy News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years.

“When I use a word, it means just what I choose it to mean…” – Humpty Dumpty

Even after all these years, I’m still surprised to learn new ways the words we use every day can mean different things to patients to whom we say them.

Take the word “biopsy.” To a dermatologist, it means “a test of a piece of tissue” (in our case, of skin), to help find out what the problem is.

I’ve always known that to many patients, the word “biopsy” suggests cancer, or at least the concern that there may be cancer, because cancer is the context in which most people hear the word: breast biopsy, prostate biopsy, and so on. It can therefore be useful to point out to patients when a biopsy is performed for diagnostic purposes and cancer is not even on the list of possibilities.

Lately, though, I’ve had a few encounters that highlighted other interesting ways the word “biopsy” can be misunderstood.

Case 1: Arnold the Irritated

“Arnold,” I say. “I need to biopsy this. Based on the results, it may need further treatment, but I doubt it.”

“I thought you were taking it off now,” says Arnold.

“No, I’m testing it, “I say.

“But I want it off,” says Arnold. “It gets irritated when I shave over it, so I want it off.”

“Yes,” I say, “but in order to remove it properly, I need to know what it is.”

“What?”

We have to go around a few more times before Arnold catches on.

Case 2: Gaetano the Outraged

“Gaetano is on the phone,” says my billing clerk. “He says you told him you weren’t going to biopsy his spot, and then he got a bill from the pathology lab.”

I call Gaetano. “You said you weren’t going to biopsy this,” he says. “You said you were sure you knew what it was, so you didn’t have to biopsy it.”

“First of all,” I explain, “I’m never totally sure. Your spot looked like a basal cell skin cancer, and that’s what it turned out to be. But I’ve had cases where the pathology results surprised me, and it turned out to be something less – or something more. So I have to check the biopsy.”

“I understand, Doctor” says Gaetano.

“In addition,” I go on, “what I actually meant to say was that I was not going to only take a biopsy of the spot. I was going to remove it completely, so that if my diagnosis was confirmed, you wouldn’t have to come back and have more done. Sorry if I didn’t make that clear.”

“So you biopsied it,” says Gaetano, but you didn’t just biopsy it. I get it. I think.”

Good for you, Gaetano. Next time I am going to – actually, next time I don’t know what I’ll do.

Case 3: Melvin the Clueless

“I understand your former dermatologist removed something from your arm,” I say to Melvin.

“Yes, they took a biopsy, and then they removed it,” says Melvin. “I just have one question.”

“What is that?” I ask.

“Which was the biopsy?” asks Melvin, “the first or the second?”

I didn’t let on, but inside I was shaking my head.

Even with the best will on both sides – and even if both are native speakers of the same language – there are just so many ways people can misunderstand each other. Humpty Dumpty was wrong. Words can mean what both the talker and the listener think they mean. Humpty Dumpty probably didn’t get out much.

Never biopsy an egg. 

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Skin & Allergy News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years.

“When I use a word, it means just what I choose it to mean…” – Humpty Dumpty

Even after all these years, I’m still surprised to learn new ways the words we use every day can mean different things to patients to whom we say them.

Take the word “biopsy.” To a dermatologist, it means “a test of a piece of tissue” (in our case, of skin), to help find out what the problem is.

I’ve always known that to many patients, the word “biopsy” suggests cancer, or at least the concern that there may be cancer, because cancer is the context in which most people hear the word: breast biopsy, prostate biopsy, and so on. It can therefore be useful to point out to patients when a biopsy is performed for diagnostic purposes and cancer is not even on the list of possibilities.

Lately, though, I’ve had a few encounters that highlighted other interesting ways the word “biopsy” can be misunderstood.

Case 1: Arnold the Irritated

“Arnold,” I say. “I need to biopsy this. Based on the results, it may need further treatment, but I doubt it.”

“I thought you were taking it off now,” says Arnold.

“No, I’m testing it, “I say.

“But I want it off,” says Arnold. “It gets irritated when I shave over it, so I want it off.”

“Yes,” I say, “but in order to remove it properly, I need to know what it is.”

“What?”

We have to go around a few more times before Arnold catches on.

Case 2: Gaetano the Outraged

“Gaetano is on the phone,” says my billing clerk. “He says you told him you weren’t going to biopsy his spot, and then he got a bill from the pathology lab.”

I call Gaetano. “You said you weren’t going to biopsy this,” he says. “You said you were sure you knew what it was, so you didn’t have to biopsy it.”

“First of all,” I explain, “I’m never totally sure. Your spot looked like a basal cell skin cancer, and that’s what it turned out to be. But I’ve had cases where the pathology results surprised me, and it turned out to be something less – or something more. So I have to check the biopsy.”

“I understand, Doctor” says Gaetano.

“In addition,” I go on, “what I actually meant to say was that I was not going to only take a biopsy of the spot. I was going to remove it completely, so that if my diagnosis was confirmed, you wouldn’t have to come back and have more done. Sorry if I didn’t make that clear.”

“So you biopsied it,” says Gaetano, but you didn’t just biopsy it. I get it. I think.”

Good for you, Gaetano. Next time I am going to – actually, next time I don’t know what I’ll do.

Case 3: Melvin the Clueless

“I understand your former dermatologist removed something from your arm,” I say to Melvin.

“Yes, they took a biopsy, and then they removed it,” says Melvin. “I just have one question.”

“What is that?” I ask.

“Which was the biopsy?” asks Melvin, “the first or the second?”

I didn’t let on, but inside I was shaking my head.

Even with the best will on both sides – and even if both are native speakers of the same language – there are just so many ways people can misunderstand each other. Humpty Dumpty was wrong. Words can mean what both the talker and the listener think they mean. Humpty Dumpty probably didn’t get out much.

Never biopsy an egg. 

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Skin & Allergy News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years.

Question: Your office assistant misfiled a critical laboratory report showing dangerous hyperkalemia of 6.5 mEq/L. Unaware of the abnormality, you failed to notify the end-stage renal patient to return for treatment. In the meantime, the patient collapsed and died, and an autopsy revealed a fresh transmural myocardial infarct.

Which of the following statements is best?

A. You are negligent, because the standard of care is to promptly contact the patient.

B. Your office assistant is negligent, because she was the one who misfiled the report.

C. Liability rests with the laboratory, because it should have called the office immediately with the critical value.

D. Your lawyer will defend you on the legal theory that hyperkalemia was not the proximate cause of death.

E. All of the above.

Answer: E. In any negligence action, the plaintiff bears the burden of proof, on a balance of probabilities, that the defendant owes him/her a duty of care, the breach of which proximately caused the plaintiff’s injuries.

One begins with an inquiry into whether a duty exists and whether a breach has occurred. Generally, doctors owe a legal duty of due care to their patients arising out of the doctor-patient relationship. By “missing” the laboratory report, especially one of urgency, and not immediately notifying the patient, the doctor has likely breached his/her duty. Another way of putting it is to ask whether the conduct has fallen below what is ordinarily expected of a practitioner in a similar situation.

The doctor will likely blame the office assistant for misfiling the report, and the assistant is indeed liable, as he/she also owes a direct legal duty to the patient. However, such liability will then fall upon the doctor under “respondeat superior” or “let the master answer,” which is the legal doctrine underpinning vicarious liability. This is characteristically seen in an employer-employee situation, where liability is imputed to the employer despite the tortious act being committed only by the employee.

The idea behind this rule is to ensure that the employer, as supervisor, will enforce proper work conditions to avoid risk of harm. The employer also is better able to shoulder the cost of compensating the victim.

For vicarious liability to arise, the employee’s act must have occurred during and within the scope of employment, and the risk of harm must be foreseeable. Under the facts of this hypothetical scenario, it is easy to see that the doctor will be vicariously liable for the negligent act of the assistant.

The clinical laboratory also owes an independent duty to the patient, which includes, among other things, assuring the proper standards in specimen collection and test performance. The duty extends to timely and accurate reporting of the results, including calling the physician when there is a critically high or low value if that is the standard of care in the community, as it generally is.

Thus, the laboratory in this case will likely be named as a codefendant. This is called joint and several liability, where more than one defendant has concurrently or successively caused a plaintiff’s indivisible injury, and the latter can recover all damages from any of the wrongdoers irrespective of degree of fault, as long as causation is proven. However, the plaintiff is not entitled to double recovery, and a defendant can proceed against the other liable parties for contribution.

Proving existence and breach of duty are necessary but insufficient steps toward winning the lawsuit. The plaintiff must also establish causation, i.e., that the substandard care caused the injury.

Causation inquires into both cause-in-fact and cause-in-law, and the term “proximate cause” is used to cover both of these aspects of causation. Cause-in-fact is established with the “but for” test – whether it can be said that had it not been for the defendant’s actions, the plaintiff would not have suffered the injury.

In this scenario, the doctor’s attorney will argue that the cause of death, a myocardial infarct, was preexisting atherosclerotic heart disease, rather than hyperkalemia. Besides, the chronic renal patient typically adapts to hyperkalemia and can tolerate elevated levels better than nonrenal patients. Of course, the counterargument is that the patient’s cardiac injury was a likely consequence of hyperkalemia-induced ventricular arrhythmia.

The doctor, the nurse, and the laboratory will all be named as codefendants. However, the laboratory will attempt to escape liability by arguing that its negligence, if any, was superseded by the doctor’s own negligent failure to read the report. Cause-in-law analysis examines whether a new independent event has intervened between the negligent act and the outcome, which may have been aggravated by the new event.

It naturally raises the question whether the original wrongdoer – in this case, the laboratory – continues to be liable, or whether the chain of causation has been broken by the intervening cause (the doctor’s negligence).

In a federal case, the Florida District Court of Appeals found several doctors liable for missing the diagnosis of tuberculous meningitis (Hadley v. Terwilleger, 873 So.2d 378 (Fl. 2004)). The doctors had seen the patient at various times in a sequential manner. The court held that the plaintiff was entitled to concurring-cause, rather than superseding-cause, jury instructions. The purpose of such instruction was to negate the idea that a defendant is excused from the consequences of his or her negligence by reason of some other cause concurring in time and contributing to the same injury.

Overlooked, misfiled, or otherwise “missed” laboratory or x-ray reports are commonly encountered in medical practice, and may lead in some instances to serious patient injury. They are typically systems errors rather than the fault of any single individual, and like most medical errors, largely preventable.

Physicians and health care institutions should put in place tested protocols that protect patients from risk of harm, and, as the Institute of Medicine stated in its 2000 report, “To Err Is Human: Building a Safer Health System,” move away from “a culture of blame to a culture of safety.”

Dr. Tan is professor emeritus of medicine and former adjunct professor of law at the University of Hawaii, and currently directs the St. Francis International Center for Healthcare Ethics in Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. Some of the articles in this series are adapted from the author’s 2006 book, “Medical Malpractice: Understanding the Law, Managing the Risk,” and his 2012 Halsbury treatise, “Medical Negligence and Professional Misconduct.” For additional information, readers may contact the author at s[email protected].

Question: Your office assistant misfiled a critical laboratory report showing dangerous hyperkalemia of 6.5 mEq/L. Unaware of the abnormality, you failed to notify the end-stage renal patient to return for treatment. In the meantime, the patient collapsed and died, and an autopsy revealed a fresh transmural myocardial infarct.

Which of the following statements is best?

A. You are negligent, because the standard of care is to promptly contact the patient.

B. Your office assistant is negligent, because she was the one who misfiled the report.

C. Liability rests with the laboratory, because it should have called the office immediately with the critical value.

D. Your lawyer will defend you on the legal theory that hyperkalemia was not the proximate cause of death.

E. All of the above.

Answer: E. In any negligence action, the plaintiff bears the burden of proof, on a balance of probabilities, that the defendant owes him/her a duty of care, the breach of which proximately caused the plaintiff’s injuries.

One begins with an inquiry into whether a duty exists and whether a breach has occurred. Generally, doctors owe a legal duty of due care to their patients arising out of the doctor-patient relationship. By “missing” the laboratory report, especially one of urgency, and not immediately notifying the patient, the doctor has likely breached his/her duty. Another way of putting it is to ask whether the conduct has fallen below what is ordinarily expected of a practitioner in a similar situation.

The doctor will likely blame the office assistant for misfiling the report, and the assistant is indeed liable, as he/she also owes a direct legal duty to the patient. However, such liability will then fall upon the doctor under “respondeat superior” or “let the master answer,” which is the legal doctrine underpinning vicarious liability. This is characteristically seen in an employer-employee situation, where liability is imputed to the employer despite the tortious act being committed only by the employee.

The idea behind this rule is to ensure that the employer, as supervisor, will enforce proper work conditions to avoid risk of harm. The employer also is better able to shoulder the cost of compensating the victim.

For vicarious liability to arise, the employee’s act must have occurred during and within the scope of employment, and the risk of harm must be foreseeable. Under the facts of this hypothetical scenario, it is easy to see that the doctor will be vicariously liable for the negligent act of the assistant.

The clinical laboratory also owes an independent duty to the patient, which includes, among other things, assuring the proper standards in specimen collection and test performance. The duty extends to timely and accurate reporting of the results, including calling the physician when there is a critically high or low value if that is the standard of care in the community, as it generally is.

Thus, the laboratory in this case will likely be named as a codefendant. This is called joint and several liability, where more than one defendant has concurrently or successively caused a plaintiff’s indivisible injury, and the latter can recover all damages from any of the wrongdoers irrespective of degree of fault, as long as causation is proven. However, the plaintiff is not entitled to double recovery, and a defendant can proceed against the other liable parties for contribution.

Proving existence and breach of duty are necessary but insufficient steps toward winning the lawsuit. The plaintiff must also establish causation, i.e., that the substandard care caused the injury.

Causation inquires into both cause-in-fact and cause-in-law, and the term “proximate cause” is used to cover both of these aspects of causation. Cause-in-fact is established with the “but for” test – whether it can be said that had it not been for the defendant’s actions, the plaintiff would not have suffered the injury.

In this scenario, the doctor’s attorney will argue that the cause of death, a myocardial infarct, was preexisting atherosclerotic heart disease, rather than hyperkalemia. Besides, the chronic renal patient typically adapts to hyperkalemia and can tolerate elevated levels better than nonrenal patients. Of course, the counterargument is that the patient’s cardiac injury was a likely consequence of hyperkalemia-induced ventricular arrhythmia.

The doctor, the nurse, and the laboratory will all be named as codefendants. However, the laboratory will attempt to escape liability by arguing that its negligence, if any, was superseded by the doctor’s own negligent failure to read the report. Cause-in-law analysis examines whether a new independent event has intervened between the negligent act and the outcome, which may have been aggravated by the new event.

It naturally raises the question whether the original wrongdoer – in this case, the laboratory – continues to be liable, or whether the chain of causation has been broken by the intervening cause (the doctor’s negligence).

In a federal case, the Florida District Court of Appeals found several doctors liable for missing the diagnosis of tuberculous meningitis (Hadley v. Terwilleger, 873 So.2d 378 (Fl. 2004)). The doctors had seen the patient at various times in a sequential manner. The court held that the plaintiff was entitled to concurring-cause, rather than superseding-cause, jury instructions. The purpose of such instruction was to negate the idea that a defendant is excused from the consequences of his or her negligence by reason of some other cause concurring in time and contributing to the same injury.

Overlooked, misfiled, or otherwise “missed” laboratory or x-ray reports are commonly encountered in medical practice, and may lead in some instances to serious patient injury. They are typically systems errors rather than the fault of any single individual, and like most medical errors, largely preventable.

Physicians and health care institutions should put in place tested protocols that protect patients from risk of harm, and, as the Institute of Medicine stated in its 2000 report, “To Err Is Human: Building a Safer Health System,” move away from “a culture of blame to a culture of safety.”

Dr. Tan is professor emeritus of medicine and former adjunct professor of law at the University of Hawaii, and currently directs the St. Francis International Center for Healthcare Ethics in Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. Some of the articles in this series are adapted from the author’s 2006 book, “Medical Malpractice: Understanding the Law, Managing the Risk,” and his 2012 Halsbury treatise, “Medical Negligence and Professional Misconduct.” For additional information, readers may contact the author at s[email protected].

Question: Your office assistant misfiled a critical laboratory report showing dangerous hyperkalemia of 6.5 mEq/L. Unaware of the abnormality, you failed to notify the end-stage renal patient to return for treatment. In the meantime, the patient collapsed and died, and an autopsy revealed a fresh transmural myocardial infarct.

Which of the following statements is best?

A. You are negligent, because the standard of care is to promptly contact the patient.

B. Your office assistant is negligent, because she was the one who misfiled the report.

C. Liability rests with the laboratory, because it should have called the office immediately with the critical value.

D. Your lawyer will defend you on the legal theory that hyperkalemia was not the proximate cause of death.

E. All of the above.

Answer: E. In any negligence action, the plaintiff bears the burden of proof, on a balance of probabilities, that the defendant owes him/her a duty of care, the breach of which proximately caused the plaintiff’s injuries.

One begins with an inquiry into whether a duty exists and whether a breach has occurred. Generally, doctors owe a legal duty of due care to their patients arising out of the doctor-patient relationship. By “missing” the laboratory report, especially one of urgency, and not immediately notifying the patient, the doctor has likely breached his/her duty. Another way of putting it is to ask whether the conduct has fallen below what is ordinarily expected of a practitioner in a similar situation.

The doctor will likely blame the office assistant for misfiling the report, and the assistant is indeed liable, as he/she also owes a direct legal duty to the patient. However, such liability will then fall upon the doctor under “respondeat superior” or “let the master answer,” which is the legal doctrine underpinning vicarious liability. This is characteristically seen in an employer-employee situation, where liability is imputed to the employer despite the tortious act being committed only by the employee.

The idea behind this rule is to ensure that the employer, as supervisor, will enforce proper work conditions to avoid risk of harm. The employer also is better able to shoulder the cost of compensating the victim.

For vicarious liability to arise, the employee’s act must have occurred during and within the scope of employment, and the risk of harm must be foreseeable. Under the facts of this hypothetical scenario, it is easy to see that the doctor will be vicariously liable for the negligent act of the assistant.

The clinical laboratory also owes an independent duty to the patient, which includes, among other things, assuring the proper standards in specimen collection and test performance. The duty extends to timely and accurate reporting of the results, including calling the physician when there is a critically high or low value if that is the standard of care in the community, as it generally is.

Thus, the laboratory in this case will likely be named as a codefendant. This is called joint and several liability, where more than one defendant has concurrently or successively caused a plaintiff’s indivisible injury, and the latter can recover all damages from any of the wrongdoers irrespective of degree of fault, as long as causation is proven. However, the plaintiff is not entitled to double recovery, and a defendant can proceed against the other liable parties for contribution.

Proving existence and breach of duty are necessary but insufficient steps toward winning the lawsuit. The plaintiff must also establish causation, i.e., that the substandard care caused the injury.

Causation inquires into both cause-in-fact and cause-in-law, and the term “proximate cause” is used to cover both of these aspects of causation. Cause-in-fact is established with the “but for” test – whether it can be said that had it not been for the defendant’s actions, the plaintiff would not have suffered the injury.

In this scenario, the doctor’s attorney will argue that the cause of death, a myocardial infarct, was preexisting atherosclerotic heart disease, rather than hyperkalemia. Besides, the chronic renal patient typically adapts to hyperkalemia and can tolerate elevated levels better than nonrenal patients. Of course, the counterargument is that the patient’s cardiac injury was a likely consequence of hyperkalemia-induced ventricular arrhythmia.

The doctor, the nurse, and the laboratory will all be named as codefendants. However, the laboratory will attempt to escape liability by arguing that its negligence, if any, was superseded by the doctor’s own negligent failure to read the report. Cause-in-law analysis examines whether a new independent event has intervened between the negligent act and the outcome, which may have been aggravated by the new event.

It naturally raises the question whether the original wrongdoer – in this case, the laboratory – continues to be liable, or whether the chain of causation has been broken by the intervening cause (the doctor’s negligence).

In a federal case, the Florida District Court of Appeals found several doctors liable for missing the diagnosis of tuberculous meningitis (Hadley v. Terwilleger, 873 So.2d 378 (Fl. 2004)). The doctors had seen the patient at various times in a sequential manner. The court held that the plaintiff was entitled to concurring-cause, rather than superseding-cause, jury instructions. The purpose of such instruction was to negate the idea that a defendant is excused from the consequences of his or her negligence by reason of some other cause concurring in time and contributing to the same injury.

Overlooked, misfiled, or otherwise “missed” laboratory or x-ray reports are commonly encountered in medical practice, and may lead in some instances to serious patient injury. They are typically systems errors rather than the fault of any single individual, and like most medical errors, largely preventable.

Physicians and health care institutions should put in place tested protocols that protect patients from risk of harm, and, as the Institute of Medicine stated in its 2000 report, “To Err Is Human: Building a Safer Health System,” move away from “a culture of blame to a culture of safety.”

Dr. Tan is professor emeritus of medicine and former adjunct professor of law at the University of Hawaii, and currently directs the St. Francis International Center for Healthcare Ethics in Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. Some of the articles in this series are adapted from the author’s 2006 book, “Medical Malpractice: Understanding the Law, Managing the Risk,” and his 2012 Halsbury treatise, “Medical Negligence and Professional Misconduct.” For additional information, readers may contact the author at s[email protected].

CHICAGO – Nearly one in seven patients in U.S. ambulatory cardiology practices who would have been recommended for initiation or intensification of antihypertensive drug therapy under the 2003 Seventh Joint National Committee guidelines are no longer treatment candidates under the 2014 expert panel recommendations.

These patients who no longer qualify for antihypertensive therapy under the 2014 guidelines turn out to have a disturbingly high average estimated 10-year risk of cardiovascular events. As a result, widespread adoption of the 2014 expert panel recommendations could have major adverse consequences for cardiovascular health, Dr. William B. Borden cautioned at the American Heart Association scientific sessions.

“Given the size and underlying cardiovascular risk of the population affected by the changes in the 2014 panel recommendations, close monitoring will be required to assess changes in practice patterns, blood pressure control, and – importantly – any changes in cardiovascular morbidity and mortality,” said Dr. Borden, a cardiologist at George Washington University in Washington.

Because the 2014 expert panel guidelines represent a major shift in hypertension management, Dr. Borden and coinvestigators sought to quantify the potential cardiovascular health impact of this more lenient treatment approach. For this purpose they turned to the National Cardiovascular Data Registry Practice Innovation and Clinical Excellence (NCDR PINNACLE) Registry, a voluntary quality improvement project involving outpatient cardiology practices.

Of 1,185,253 patients with hypertension as identified in their chart by a recorded diagnosis or notation of blood pressure greater than 140/90 mm Hg, 60% met the 2003 JNC 7 goals (JAMA 2003;289:2560-72), meaning the other 40% were candidates for initiation or intensification of antihypertensive therapy in order to achieve those goals (see chart). In contrast, 74% of hypertensive patients in U.S. cardiology practices met the less aggressive targets recommended in the 2014 expert panel report (JAMA 2014;311:502-20).

Thus, fewer than two-thirds of hypertensive patients in outpatient cardiology practices met the 2003 JNC 7 blood pressure targets, while three-quarters met the liberalized 2014 targets.

Dr. Borden and coworkers zeroed in on the 15% of hypertensive patients – that’s fully 173,519 individuals in cardiology practices participating in the PINNACLE Registry – who would have been eligible for treatment under the JNC 7 recommendations but not the 2014 expert panel guidelines. Interestingly, that 15% figure was closely similar to the 17% rate reported by Dr. Michael D. Miedema of the Minneapolis Heart Institute in an analysis of a more primary care population of older patients in the Atherosclerosis Risk in Communities (ARIC) study he presented in the same session.

Dr. Borden and coinvestigators determined from medical records that the PINNACLE Registry group whose antihypertensive therapy treatment status changed between the two guidelines was at substantial baseline cardiovascular risk: Nearly two-thirds had been diagnosed with CAD, 54% had diabetes, 27% had a history of heart failure, 25% had a prior MI, and 23% had a prior transient ischemic attack or stroke.

This large group of patients who fell through the cracks between two conflicting sets of guidelines turned out to have a mean 10-year Framingham Risk Score of 8.5%. Upon incorporating the patients’ stroke risk using the atherosclerotic cardiovascular disease (ASCVD) risk score embedded in the 2013 ACC/AHA cholesterol management guidelines, their 10-year risk shot up to 28%.

The investigators then conducted a modeling exercise aimed at estimating the clinical impact of lowering systolic blood pressure in the elderly from about 150 mm Hg, as recommended in the 2014 expert panel guidelines, to about 140 mm Hg, as was the goal in JNC 7. To do so they extrapolated from the results of two randomized controlled clinical trials: the Systolic Hypertension in the Elderly Program (SHEP) and the Hypertension in the Very Elderly Trial (HYVET).

The result? Extrapolating from SHEP data, the 10-year ASCVD risk in these real-world elderly hypertensive patients caught between two conflicting sets of guidelines would drop from 28% to 19%. Using HYVET data, the average 10-year ASCVD risk would fall to 18.4%.

“This is equivalent to a number-needed-to-treat of 10-11 patients for 10 years in order to prevent one cardiovascular event,” according to Dr. Borden.

For the more than 80,000 patients over age 60 in the study population, that works out to roughly 8,000 cardiovascular events averted over the course of 10 years, he added.

The 2014 expert panel recommendations were based on a strict evidence-based review of published randomized controlled trials. The guidelines are new enough that it remains unclear if they will be embraced by clinicians or incorporated into performance measures and value-based health care purchasing programs.

The 2014 guidelines are considered highly controversial. The guideline committee comprising some of the nation’s top hypertension researchers was initially convened to come up with what was intended to be the long-awaited JNC 8 report; however, in the midst of the process the sponsoring National Heart, Lung, and Blood Institute declared it was getting out of the guideline-writing business altogether. As a result, the guidelines ultimately published carried the imprimatur of “the 2014 expert panel,” rather than the more prestigious official stamp of JNC 8.

Indeed, five members of the guideline panel felt strongly enough to break away and issued a minority report (Ann. Intern. Med. 2014;160:499-503) in which they argued there is insufficient evidence of harm stemming from the JNC 7 goal of 140/90 mm Hg in patients over age 60 to justify revising the target to 150/90. They warned that this step could reverse the impressive reductions in cardiovascular and cerebrovascular morbidity and mortality realized in recent decades. And they concluded that the burden of proof should be on those who advocate raising the treatment threshold to 150/90 mm Hg to demonstrate that it has benefit in patients over age 60, which they haven’t done.

“I’m very concerned about the [2014 expert panel] guidelines. Older individuals have the highest prevalence of hypertension, they’re the least adequately controlled, and based on the available data I’m concerned that if people follow the new guidelines there’s going to be an increase in cardiovascular events,” said Dr. Wilbert F. Aronow of New York Medical College, Valhalla, who chaired the writing committee for the first-ever ACC/AHA clinical guidelines for controlling high blood pressure in the elderly (J. Am. Coll. Cardiol. 2011;57:2037-114).

The NCDR PINNACLE Registry and this study were supported by the American College of Cardiology Foundation. Dr. Borden and Dr. Aronow reported having no financial conflicts.

[email protected] 


CHICAGO – Nearly one in seven patients in U.S. ambulatory cardiology practices who would have been recommended for initiation or intensification of antihypertensive drug therapy under the 2003 Seventh Joint National Committee guidelines are no longer treatment candidates under the 2014 expert panel recommendations.

These patients who no longer qualify for antihypertensive therapy under the 2014 guidelines turn out to have a disturbingly high average estimated 10-year risk of cardiovascular events. As a result, widespread adoption of the 2014 expert panel recommendations could have major adverse consequences for cardiovascular health, Dr. William B. Borden cautioned at the American Heart Association scientific sessions.

“Given the size and underlying cardiovascular risk of the population affected by the changes in the 2014 panel recommendations, close monitoring will be required to assess changes in practice patterns, blood pressure control, and – importantly – any changes in cardiovascular morbidity and mortality,” said Dr. Borden, a cardiologist at George Washington University in Washington.

Because the 2014 expert panel guidelines represent a major shift in hypertension management, Dr. Borden and coinvestigators sought to quantify the potential cardiovascular health impact of this more lenient treatment approach. For this purpose they turned to the National Cardiovascular Data Registry Practice Innovation and Clinical Excellence (NCDR PINNACLE) Registry, a voluntary quality improvement project involving outpatient cardiology practices.

Of 1,185,253 patients with hypertension as identified in their chart by a recorded diagnosis or notation of blood pressure greater than 140/90 mm Hg, 60% met the 2003 JNC 7 goals (JAMA 2003;289:2560-72), meaning the other 40% were candidates for initiation or intensification of antihypertensive therapy in order to achieve those goals (see chart). In contrast, 74% of hypertensive patients in U.S. cardiology practices met the less aggressive targets recommended in the 2014 expert panel report (JAMA 2014;311:502-20).

Thus, fewer than two-thirds of hypertensive patients in outpatient cardiology practices met the 2003 JNC 7 blood pressure targets, while three-quarters met the liberalized 2014 targets.

Dr. Borden and coworkers zeroed in on the 15% of hypertensive patients – that’s fully 173,519 individuals in cardiology practices participating in the PINNACLE Registry – who would have been eligible for treatment under the JNC 7 recommendations but not the 2014 expert panel guidelines. Interestingly, that 15% figure was closely similar to the 17% rate reported by Dr. Michael D. Miedema of the Minneapolis Heart Institute in an analysis of a more primary care population of older patients in the Atherosclerosis Risk in Communities (ARIC) study he presented in the same session.

Dr. Borden and coinvestigators determined from medical records that the PINNACLE Registry group whose antihypertensive therapy treatment status changed between the two guidelines was at substantial baseline cardiovascular risk: Nearly two-thirds had been diagnosed with CAD, 54% had diabetes, 27% had a history of heart failure, 25% had a prior MI, and 23% had a prior transient ischemic attack or stroke.

This large group of patients who fell through the cracks between two conflicting sets of guidelines turned out to have a mean 10-year Framingham Risk Score of 8.5%. Upon incorporating the patients’ stroke risk using the atherosclerotic cardiovascular disease (ASCVD) risk score embedded in the 2013 ACC/AHA cholesterol management guidelines, their 10-year risk shot up to 28%.

The investigators then conducted a modeling exercise aimed at estimating the clinical impact of lowering systolic blood pressure in the elderly from about 150 mm Hg, as recommended in the 2014 expert panel guidelines, to about 140 mm Hg, as was the goal in JNC 7. To do so they extrapolated from the results of two randomized controlled clinical trials: the Systolic Hypertension in the Elderly Program (SHEP) and the Hypertension in the Very Elderly Trial (HYVET).

The result? Extrapolating from SHEP data, the 10-year ASCVD risk in these real-world elderly hypertensive patients caught between two conflicting sets of guidelines would drop from 28% to 19%. Using HYVET data, the average 10-year ASCVD risk would fall to 18.4%.

“This is equivalent to a number-needed-to-treat of 10-11 patients for 10 years in order to prevent one cardiovascular event,” according to Dr. Borden.

For the more than 80,000 patients over age 60 in the study population, that works out to roughly 8,000 cardiovascular events averted over the course of 10 years, he added.

The 2014 expert panel recommendations were based on a strict evidence-based review of published randomized controlled trials. The guidelines are new enough that it remains unclear if they will be embraced by clinicians or incorporated into performance measures and value-based health care purchasing programs.

The 2014 guidelines are considered highly controversial. The guideline committee comprising some of the nation’s top hypertension researchers was initially convened to come up with what was intended to be the long-awaited JNC 8 report; however, in the midst of the process the sponsoring National Heart, Lung, and Blood Institute declared it was getting out of the guideline-writing business altogether. As a result, the guidelines ultimately published carried the imprimatur of “the 2014 expert panel,” rather than the more prestigious official stamp of JNC 8.

Indeed, five members of the guideline panel felt strongly enough to break away and issued a minority report (Ann. Intern. Med. 2014;160:499-503) in which they argued there is insufficient evidence of harm stemming from the JNC 7 goal of 140/90 mm Hg in patients over age 60 to justify revising the target to 150/90. They warned that this step could reverse the impressive reductions in cardiovascular and cerebrovascular morbidity and mortality realized in recent decades. And they concluded that the burden of proof should be on those who advocate raising the treatment threshold to 150/90 mm Hg to demonstrate that it has benefit in patients over age 60, which they haven’t done.

“I’m very concerned about the [2014 expert panel] guidelines. Older individuals have the highest prevalence of hypertension, they’re the least adequately controlled, and based on the available data I’m concerned that if people follow the new guidelines there’s going to be an increase in cardiovascular events,” said Dr. Wilbert F. Aronow of New York Medical College, Valhalla, who chaired the writing committee for the first-ever ACC/AHA clinical guidelines for controlling high blood pressure in the elderly (J. Am. Coll. Cardiol. 2011;57:2037-114).

The NCDR PINNACLE Registry and this study were supported by the American College of Cardiology Foundation. Dr. Borden and Dr. Aronow reported having no financial conflicts.

[email protected] 


CHICAGO – Nearly one in seven patients in U.S. ambulatory cardiology practices who would have been recommended for initiation or intensification of antihypertensive drug therapy under the 2003 Seventh Joint National Committee guidelines are no longer treatment candidates under the 2014 expert panel recommendations.

These patients who no longer qualify for antihypertensive therapy under the 2014 guidelines turn out to have a disturbingly high average estimated 10-year risk of cardiovascular events. As a result, widespread adoption of the 2014 expert panel recommendations could have major adverse consequences for cardiovascular health, Dr. William B. Borden cautioned at the American Heart Association scientific sessions.

“Given the size and underlying cardiovascular risk of the population affected by the changes in the 2014 panel recommendations, close monitoring will be required to assess changes in practice patterns, blood pressure control, and – importantly – any changes in cardiovascular morbidity and mortality,” said Dr. Borden, a cardiologist at George Washington University in Washington.

Because the 2014 expert panel guidelines represent a major shift in hypertension management, Dr. Borden and coinvestigators sought to quantify the potential cardiovascular health impact of this more lenient treatment approach. For this purpose they turned to the National Cardiovascular Data Registry Practice Innovation and Clinical Excellence (NCDR PINNACLE) Registry, a voluntary quality improvement project involving outpatient cardiology practices.

Of 1,185,253 patients with hypertension as identified in their chart by a recorded diagnosis or notation of blood pressure greater than 140/90 mm Hg, 60% met the 2003 JNC 7 goals (JAMA 2003;289:2560-72), meaning the other 40% were candidates for initiation or intensification of antihypertensive therapy in order to achieve those goals (see chart). In contrast, 74% of hypertensive patients in U.S. cardiology practices met the less aggressive targets recommended in the 2014 expert panel report (JAMA 2014;311:502-20).

Thus, fewer than two-thirds of hypertensive patients in outpatient cardiology practices met the 2003 JNC 7 blood pressure targets, while three-quarters met the liberalized 2014 targets.

Dr. Borden and coworkers zeroed in on the 15% of hypertensive patients – that’s fully 173,519 individuals in cardiology practices participating in the PINNACLE Registry – who would have been eligible for treatment under the JNC 7 recommendations but not the 2014 expert panel guidelines. Interestingly, that 15% figure was closely similar to the 17% rate reported by Dr. Michael D. Miedema of the Minneapolis Heart Institute in an analysis of a more primary care population of older patients in the Atherosclerosis Risk in Communities (ARIC) study he presented in the same session.

Dr. Borden and coinvestigators determined from medical records that the PINNACLE Registry group whose antihypertensive therapy treatment status changed between the two guidelines was at substantial baseline cardiovascular risk: Nearly two-thirds had been diagnosed with CAD, 54% had diabetes, 27% had a history of heart failure, 25% had a prior MI, and 23% had a prior transient ischemic attack or stroke.

This large group of patients who fell through the cracks between two conflicting sets of guidelines turned out to have a mean 10-year Framingham Risk Score of 8.5%. Upon incorporating the patients’ stroke risk using the atherosclerotic cardiovascular disease (ASCVD) risk score embedded in the 2013 ACC/AHA cholesterol management guidelines, their 10-year risk shot up to 28%.

The investigators then conducted a modeling exercise aimed at estimating the clinical impact of lowering systolic blood pressure in the elderly from about 150 mm Hg, as recommended in the 2014 expert panel guidelines, to about 140 mm Hg, as was the goal in JNC 7. To do so they extrapolated from the results of two randomized controlled clinical trials: the Systolic Hypertension in the Elderly Program (SHEP) and the Hypertension in the Very Elderly Trial (HYVET).

The result? Extrapolating from SHEP data, the 10-year ASCVD risk in these real-world elderly hypertensive patients caught between two conflicting sets of guidelines would drop from 28% to 19%. Using HYVET data, the average 10-year ASCVD risk would fall to 18.4%.

“This is equivalent to a number-needed-to-treat of 10-11 patients for 10 years in order to prevent one cardiovascular event,” according to Dr. Borden.

For the more than 80,000 patients over age 60 in the study population, that works out to roughly 8,000 cardiovascular events averted over the course of 10 years, he added.

The 2014 expert panel recommendations were based on a strict evidence-based review of published randomized controlled trials. The guidelines are new enough that it remains unclear if they will be embraced by clinicians or incorporated into performance measures and value-based health care purchasing programs.

The 2014 guidelines are considered highly controversial. The guideline committee comprising some of the nation’s top hypertension researchers was initially convened to come up with what was intended to be the long-awaited JNC 8 report; however, in the midst of the process the sponsoring National Heart, Lung, and Blood Institute declared it was getting out of the guideline-writing business altogether. As a result, the guidelines ultimately published carried the imprimatur of “the 2014 expert panel,” rather than the more prestigious official stamp of JNC 8.

Indeed, five members of the guideline panel felt strongly enough to break away and issued a minority report (Ann. Intern. Med. 2014;160:499-503) in which they argued there is insufficient evidence of harm stemming from the JNC 7 goal of 140/90 mm Hg in patients over age 60 to justify revising the target to 150/90. They warned that this step could reverse the impressive reductions in cardiovascular and cerebrovascular morbidity and mortality realized in recent decades. And they concluded that the burden of proof should be on those who advocate raising the treatment threshold to 150/90 mm Hg to demonstrate that it has benefit in patients over age 60, which they haven’t done.

“I’m very concerned about the [2014 expert panel] guidelines. Older individuals have the highest prevalence of hypertension, they’re the least adequately controlled, and based on the available data I’m concerned that if people follow the new guidelines there’s going to be an increase in cardiovascular events,” said Dr. Wilbert F. Aronow of New York Medical College, Valhalla, who chaired the writing committee for the first-ever ACC/AHA clinical guidelines for controlling high blood pressure in the elderly (J. Am. Coll. Cardiol. 2011;57:2037-114).

The NCDR PINNACLE Registry and this study were supported by the American College of Cardiology Foundation. Dr. Borden and Dr. Aronow reported having no financial conflicts.

[email protected] 


AML cells in the bone marrow

Inhibiting the enzyme 5-lipoxygenase (5-LO) can eradicate cancer stem cell-like cells (CSCs) in acute myeloid leukemia (AML), according to a preclinical study

published in Cancer Research.

Previous research suggested the enzyme is needed to maintain CSCs in chronic myeloid leukemia.

So investigators theorized that 5-LO could be a therapeutic target for AML, as CSCs are thought to cause the spread and relapse of this disease.

To test that theory, the team evaluated the effects of 5-LO inhibition in a PML/RARα-positive model of AML. As a model of CSCs, they used Sca-1⁺/lin⁻ murine hematopoietic stem and progenitor cells (HSPCs), which were retrovirally transduced with PML/RARα.

The researchers targeted 5-LO genetically and pharmacologically. And they found that 5-LO inhibition interfered with the aberrant stem cell capacity of PML/RARα-expressing HSPCs.

Inhibiting 5-LO also inhibited Wnt signaling, which has been shown to be critical for CSC maintenance.

Additional investigation revealed that inhibition of Wnt signaling and CSCs was due to the generation of a catalytically inactive form of 5-LO, which hindered nuclear translocation of β-catenin.

Considering these results together, as well as evidence that CSCs mediate AML relapse, the investigators concluded that eradicating CSCs via 5-LO inhibition may offer a new treatment approach for AML.

“These results form the basis for a possible use of the 5-lipoxygenase inhibitors as stem cell therapy for a sustainable cure for acute myeloid leukemia,” said Martin Ruthardt, MD, of Goethe University in Frankfurt, Germany. “But this must firstly be studied further in preclinical and clinical studies in humans.”

“We are now in the process of examining the molecular mechanism in more detail in order to find out how the inhibitors precisely work on the leukemia stem cells,” added Thorsten Jürgen Maier, MD, PhD, of Goethe University and Aarhus University in Denmark. “We very much hope that our results will be of benefit for leukemia patients.”

AML cells in the bone marrow

Inhibiting the enzyme 5-lipoxygenase (5-LO) can eradicate cancer stem cell-like cells (CSCs) in acute myeloid leukemia (AML), according to a preclinical study

published in Cancer Research.

Previous research suggested the enzyme is needed to maintain CSCs in chronic myeloid leukemia.

So investigators theorized that 5-LO could be a therapeutic target for AML, as CSCs are thought to cause the spread and relapse of this disease.

To test that theory, the team evaluated the effects of 5-LO inhibition in a PML/RARα-positive model of AML. As a model of CSCs, they used Sca-1⁺/lin⁻ murine hematopoietic stem and progenitor cells (HSPCs), which were retrovirally transduced with PML/RARα.

The researchers targeted 5-LO genetically and pharmacologically. And they found that 5-LO inhibition interfered with the aberrant stem cell capacity of PML/RARα-expressing HSPCs.

Inhibiting 5-LO also inhibited Wnt signaling, which has been shown to be critical for CSC maintenance.

Additional investigation revealed that inhibition of Wnt signaling and CSCs was due to the generation of a catalytically inactive form of 5-LO, which hindered nuclear translocation of β-catenin.

Considering these results together, as well as evidence that CSCs mediate AML relapse, the investigators concluded that eradicating CSCs via 5-LO inhibition may offer a new treatment approach for AML.

“These results form the basis for a possible use of the 5-lipoxygenase inhibitors as stem cell therapy for a sustainable cure for acute myeloid leukemia,” said Martin Ruthardt, MD, of Goethe University in Frankfurt, Germany. “But this must firstly be studied further in preclinical and clinical studies in humans.”

“We are now in the process of examining the molecular mechanism in more detail in order to find out how the inhibitors precisely work on the leukemia stem cells,” added Thorsten Jürgen Maier, MD, PhD, of Goethe University and Aarhus University in Denmark. “We very much hope that our results will be of benefit for leukemia patients.”

AML cells in the bone marrow

Inhibiting the enzyme 5-lipoxygenase (5-LO) can eradicate cancer stem cell-like cells (CSCs) in acute myeloid leukemia (AML), according to a preclinical study

published in Cancer Research.

Previous research suggested the enzyme is needed to maintain CSCs in chronic myeloid leukemia.

So investigators theorized that 5-LO could be a therapeutic target for AML, as CSCs are thought to cause the spread and relapse of this disease.

To test that theory, the team evaluated the effects of 5-LO inhibition in a PML/RARα-positive model of AML. As a model of CSCs, they used Sca-1⁺/lin⁻ murine hematopoietic stem and progenitor cells (HSPCs), which were retrovirally transduced with PML/RARα.

The researchers targeted 5-LO genetically and pharmacologically. And they found that 5-LO inhibition interfered with the aberrant stem cell capacity of PML/RARα-expressing HSPCs.

Inhibiting 5-LO also inhibited Wnt signaling, which has been shown to be critical for CSC maintenance.

Additional investigation revealed that inhibition of Wnt signaling and CSCs was due to the generation of a catalytically inactive form of 5-LO, which hindered nuclear translocation of β-catenin.

Considering these results together, as well as evidence that CSCs mediate AML relapse, the investigators concluded that eradicating CSCs via 5-LO inhibition may offer a new treatment approach for AML.

“These results form the basis for a possible use of the 5-lipoxygenase inhibitors as stem cell therapy for a sustainable cure for acute myeloid leukemia,” said Martin Ruthardt, MD, of Goethe University in Frankfurt, Germany. “But this must firstly be studied further in preclinical and clinical studies in humans.”

“We are now in the process of examining the molecular mechanism in more detail in order to find out how the inhibitors precisely work on the leukemia stem cells,” added Thorsten Jürgen Maier, MD, PhD, of Goethe University and Aarhus University in Denmark. “We very much hope that our results will be of benefit for leukemia patients.”

Preparing for a clinical trial

Credit: Esther Dyson

The US Department of Health and Human Services (HHS) has proposed a rule that would require more public disclosure of clinical trial results.

The Notice of Proposed Rulemaking (NPRM) adds to current requirements for submitting trial information to ClinicalTrials.gov.

Most notably, the rule would require the submission of summary results from studies of products not yet approved by the US Food and Drug Administration

(FDA).

The National Institutes of Health (NIH) have created a draft policy that would extend similar reporting requirements to all clinical trials funded by NIH.

About the NPRM: Who, what, and when

The NPRM details new procedures for meeting the requirements established by the Food and Drug Administration Amendments Act of 2007 (FDAAA) to improve public access to clinical trial information.

The proposed rule specifies how information about a clinical trial would need to be submitted to ClinicalTrials.gov. It would not affect requirements for the design or conduct of clinical trials or for the data that must be collected during these trials.

The rule would apply to controlled, interventional studies of drugs, biological products, and devices that are regulated by the FDA. This excludes phase 1 studies of drugs and biological products and feasibility studies of devices.

In general, clinical trials of products regulated by the FDA will meet one or more of the following criteria: include one or more sites in the US; study a product manufactured in the US or its territories and exported for use in a trial outside the US; or be conducted under an FDA investigational new drug application or investigational device exemption.

The NPRM would require the parties responsible for applicable clinical trials—such as the sponsor or a designated principal investigator—to register the trial at ClinicalTrials.gov no later than 21 days after enrolling the first participant.

Registration consists of submitting 4 categories of data elements that are specified in the NPRM: 1) descriptive information, 2) recruitment information, 3) location and contact information, and 4) administrative information.

The parties responsible for the trial would also be required to submit a summary of the study’s results to ClinicalTrials.gov, generally no later than 12 months after trial completion.

However, the NPRM includes procedures for delaying results submission and for requesting extensions to the results submission deadline for good cause.

NIH policy: Extending the NPRM

The proposed NIH policy would make requirements in the NPRM applicable to all NIH-funded awardees and investigators conducting clinical trials, regardless of study phase, type of intervention, or whether they are subject to the rules proposed in the NPRM.

NIH awardees would be expected to ensure submission to ClinicalTrials.gov of the same type of registration and results information, and in the same timeframes, as responsible parties whose trials are subject to the FDAAA and the regulations proposed in the NPRM.

For clinical trials subject to only the proposed NIH policy (not the FDAAA), the NIH would post submitted information, in general, no later than 30 days after it is submitted.

An NIH-funded clinical trial that is also subject to FDAAA would need to have only one entry in ClinicalTrials.gov containing its registration and results information.

Open for comment

The public may comment on any aspect of the NPRM or the proposed NIH policy.

Written comments on the NPRM should be submitted to docket number NIH-2011-0003 at www.regulations.gov. Commenters should indicate the specific section of the NPRM to which each comment refers.

Written comments on the proposed NIH policy should be submitted to the Office of Clinical Research and Bioethics Policy, Office of Science Policy, NIH, via email at [email protected], mail at 6705 Rockledge Drive, Suite 750, Bethesda, MD 20892, or fax at 301-496-9839.

Preparing for a clinical trial

Credit: Esther Dyson

The US Department of Health and Human Services (HHS) has proposed a rule that would require more public disclosure of clinical trial results.

The Notice of Proposed Rulemaking (NPRM) adds to current requirements for submitting trial information to ClinicalTrials.gov.

Most notably, the rule would require the submission of summary results from studies of products not yet approved by the US Food and Drug Administration

(FDA).

The National Institutes of Health (NIH) have created a draft policy that would extend similar reporting requirements to all clinical trials funded by NIH.

About the NPRM: Who, what, and when

The NPRM details new procedures for meeting the requirements established by the Food and Drug Administration Amendments Act of 2007 (FDAAA) to improve public access to clinical trial information.

The proposed rule specifies how information about a clinical trial would need to be submitted to ClinicalTrials.gov. It would not affect requirements for the design or conduct of clinical trials or for the data that must be collected during these trials.

The rule would apply to controlled, interventional studies of drugs, biological products, and devices that are regulated by the FDA. This excludes phase 1 studies of drugs and biological products and feasibility studies of devices.

In general, clinical trials of products regulated by the FDA will meet one or more of the following criteria: include one or more sites in the US; study a product manufactured in the US or its territories and exported for use in a trial outside the US; or be conducted under an FDA investigational new drug application or investigational device exemption.

The NPRM would require the parties responsible for applicable clinical trials—such as the sponsor or a designated principal investigator—to register the trial at ClinicalTrials.gov no later than 21 days after enrolling the first participant.

Registration consists of submitting 4 categories of data elements that are specified in the NPRM: 1) descriptive information, 2) recruitment information, 3) location and contact information, and 4) administrative information.

The parties responsible for the trial would also be required to submit a summary of the study’s results to ClinicalTrials.gov, generally no later than 12 months after trial completion.

However, the NPRM includes procedures for delaying results submission and for requesting extensions to the results submission deadline for good cause.

NIH policy: Extending the NPRM

The proposed NIH policy would make requirements in the NPRM applicable to all NIH-funded awardees and investigators conducting clinical trials, regardless of study phase, type of intervention, or whether they are subject to the rules proposed in the NPRM.

NIH awardees would be expected to ensure submission to ClinicalTrials.gov of the same type of registration and results information, and in the same timeframes, as responsible parties whose trials are subject to the FDAAA and the regulations proposed in the NPRM.

For clinical trials subject to only the proposed NIH policy (not the FDAAA), the NIH would post submitted information, in general, no later than 30 days after it is submitted.

An NIH-funded clinical trial that is also subject to FDAAA would need to have only one entry in ClinicalTrials.gov containing its registration and results information.

Open for comment

The public may comment on any aspect of the NPRM or the proposed NIH policy.

Written comments on the NPRM should be submitted to docket number NIH-2011-0003 at www.regulations.gov. Commenters should indicate the specific section of the NPRM to which each comment refers.

Written comments on the proposed NIH policy should be submitted to the Office of Clinical Research and Bioethics Policy, Office of Science Policy, NIH, via email at [email protected], mail at 6705 Rockledge Drive, Suite 750, Bethesda, MD 20892, or fax at 301-496-9839.

Preparing for a clinical trial

Credit: Esther Dyson

The US Department of Health and Human Services (HHS) has proposed a rule that would require more public disclosure of clinical trial results.

The Notice of Proposed Rulemaking (NPRM) adds to current requirements for submitting trial information to ClinicalTrials.gov.

Most notably, the rule would require the submission of summary results from studies of products not yet approved by the US Food and Drug Administration

(FDA).

The National Institutes of Health (NIH) have created a draft policy that would extend similar reporting requirements to all clinical trials funded by NIH.

About the NPRM: Who, what, and when

The NPRM details new procedures for meeting the requirements established by the Food and Drug Administration Amendments Act of 2007 (FDAAA) to improve public access to clinical trial information.

The proposed rule specifies how information about a clinical trial would need to be submitted to ClinicalTrials.gov. It would not affect requirements for the design or conduct of clinical trials or for the data that must be collected during these trials.

The rule would apply to controlled, interventional studies of drugs, biological products, and devices that are regulated by the FDA. This excludes phase 1 studies of drugs and biological products and feasibility studies of devices.

In general, clinical trials of products regulated by the FDA will meet one or more of the following criteria: include one or more sites in the US; study a product manufactured in the US or its territories and exported for use in a trial outside the US; or be conducted under an FDA investigational new drug application or investigational device exemption.

The NPRM would require the parties responsible for applicable clinical trials—such as the sponsor or a designated principal investigator—to register the trial at ClinicalTrials.gov no later than 21 days after enrolling the first participant.

Registration consists of submitting 4 categories of data elements that are specified in the NPRM: 1) descriptive information, 2) recruitment information, 3) location and contact information, and 4) administrative information.

The parties responsible for the trial would also be required to submit a summary of the study’s results to ClinicalTrials.gov, generally no later than 12 months after trial completion.

However, the NPRM includes procedures for delaying results submission and for requesting extensions to the results submission deadline for good cause.

NIH policy: Extending the NPRM

The proposed NIH policy would make requirements in the NPRM applicable to all NIH-funded awardees and investigators conducting clinical trials, regardless of study phase, type of intervention, or whether they are subject to the rules proposed in the NPRM.

NIH awardees would be expected to ensure submission to ClinicalTrials.gov of the same type of registration and results information, and in the same timeframes, as responsible parties whose trials are subject to the FDAAA and the regulations proposed in the NPRM.

For clinical trials subject to only the proposed NIH policy (not the FDAAA), the NIH would post submitted information, in general, no later than 30 days after it is submitted.

An NIH-funded clinical trial that is also subject to FDAAA would need to have only one entry in ClinicalTrials.gov containing its registration and results information.

Open for comment

The public may comment on any aspect of the NPRM or the proposed NIH policy.

Written comments on the NPRM should be submitted to docket number NIH-2011-0003 at www.regulations.gov. Commenters should indicate the specific section of the NPRM to which each comment refers.

Written comments on the proposed NIH policy should be submitted to the Office of Clinical Research and Bioethics Policy, Office of Science Policy, NIH, via email at [email protected], mail at 6705 Rockledge Drive, Suite 750, Bethesda, MD 20892, or fax at 301-496-9839.

Micrograph showing amyloidosis

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for the oral proteasome inhibitor ixazomib (MLN9708) to treat relapsed or refractory systemic light-chain (AL) amyloidosis.

This is the first proteasome inhibitor and the first investigational therapy for AL amyloidosis to receive breakthrough designation.

Ixazomib already has orphan drug designation in the US and the European Union for this indication and to treat multiple myeloma (MM).

The FDA’s breakthrough therapy designation is intended to expedite the development and review of new medicines to treat serious or life-threatening conditions. Compounds given the designation receive more intensive FDA guidance on an efficient drug development program and an enhanced agency commitment of senior personnel.

Breakthrough therapy designation requires preliminary clinical evidence indicating the drug may demonstrate substantial improvement on a clinically significant endpoint (or endpoints) over available therapies.

The data used to support this designation for ixazomib came from a phase 1 trial that is set to be presented at the 2014 ASH Annual Meeting as abstract 3450.

The development program for ixazomib in AL amyloidosis progressed directly from a phase 1 to a phase 3 clinical trial, TOURMALINE-AL1. Ixazomib is the first oral proteasome inhibitor to enter phase 3 clinical trials, and 4 global phase 3 trials are ongoing:

• TOURMALINE-MM1, an investigation of ixazomib vs placebo in combination with lenalidomide and dexamethasone in relapsed and/or refractory MM
• TOURMALINE-AL1, an investigation of ixazomib plus dexamethasone in patients with relapsed or refractory AL amyloidosis
• TOURMALINE-MM2, an investigation of ixazomib vs placebo in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM
• TOURMALINE-MM3, an investigation of ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM following induction therapy and autologous stem cell transplant.

For additional information on the ongoing phase 3 studies, visit www.tourmalinetrials.com or www.clinicaltrials.gov. Ixazomib is under development by Millennium: the Takeda Oncology Company.

Micrograph showing amyloidosis

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for the oral proteasome inhibitor ixazomib (MLN9708) to treat relapsed or refractory systemic light-chain (AL) amyloidosis.

This is the first proteasome inhibitor and the first investigational therapy for AL amyloidosis to receive breakthrough designation.

Ixazomib already has orphan drug designation in the US and the European Union for this indication and to treat multiple myeloma (MM).

The FDA’s breakthrough therapy designation is intended to expedite the development and review of new medicines to treat serious or life-threatening conditions. Compounds given the designation receive more intensive FDA guidance on an efficient drug development program and an enhanced agency commitment of senior personnel.

Breakthrough therapy designation requires preliminary clinical evidence indicating the drug may demonstrate substantial improvement on a clinically significant endpoint (or endpoints) over available therapies.

The data used to support this designation for ixazomib came from a phase 1 trial that is set to be presented at the 2014 ASH Annual Meeting as abstract 3450.

The development program for ixazomib in AL amyloidosis progressed directly from a phase 1 to a phase 3 clinical trial, TOURMALINE-AL1. Ixazomib is the first oral proteasome inhibitor to enter phase 3 clinical trials, and 4 global phase 3 trials are ongoing:

• TOURMALINE-MM1, an investigation of ixazomib vs placebo in combination with lenalidomide and dexamethasone in relapsed and/or refractory MM
• TOURMALINE-AL1, an investigation of ixazomib plus dexamethasone in patients with relapsed or refractory AL amyloidosis
• TOURMALINE-MM2, an investigation of ixazomib vs placebo in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM
• TOURMALINE-MM3, an investigation of ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM following induction therapy and autologous stem cell transplant.

For additional information on the ongoing phase 3 studies, visit www.tourmalinetrials.com or www.clinicaltrials.gov. Ixazomib is under development by Millennium: the Takeda Oncology Company.

Micrograph showing amyloidosis

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for the oral proteasome inhibitor ixazomib (MLN9708) to treat relapsed or refractory systemic light-chain (AL) amyloidosis.

This is the first proteasome inhibitor and the first investigational therapy for AL amyloidosis to receive breakthrough designation.

Ixazomib already has orphan drug designation in the US and the European Union for this indication and to treat multiple myeloma (MM).

The FDA’s breakthrough therapy designation is intended to expedite the development and review of new medicines to treat serious or life-threatening conditions. Compounds given the designation receive more intensive FDA guidance on an efficient drug development program and an enhanced agency commitment of senior personnel.

Breakthrough therapy designation requires preliminary clinical evidence indicating the drug may demonstrate substantial improvement on a clinically significant endpoint (or endpoints) over available therapies.

The data used to support this designation for ixazomib came from a phase 1 trial that is set to be presented at the 2014 ASH Annual Meeting as abstract 3450.

The development program for ixazomib in AL amyloidosis progressed directly from a phase 1 to a phase 3 clinical trial, TOURMALINE-AL1. Ixazomib is the first oral proteasome inhibitor to enter phase 3 clinical trials, and 4 global phase 3 trials are ongoing:

• TOURMALINE-MM1, an investigation of ixazomib vs placebo in combination with lenalidomide and dexamethasone in relapsed and/or refractory MM
• TOURMALINE-AL1, an investigation of ixazomib plus dexamethasone in patients with relapsed or refractory AL amyloidosis
• TOURMALINE-MM2, an investigation of ixazomib vs placebo in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM
• TOURMALINE-MM3, an investigation of ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM following induction therapy and autologous stem cell transplant.

For additional information on the ongoing phase 3 studies, visit www.tourmalinetrials.com or www.clinicaltrials.gov. Ixazomib is under development by Millennium: the Takeda Oncology Company.

Cancer patient receiving

chemotherapy

Credit: Rhoda Baer

The UK’s National Institute for Health and Care Excellence (NICE) has updated its guidance to expand the use of erythropoiesis-stimulating agents (ESAs) in cancer patients.

In 2008, NICE issued a guidance recommending ESAs as a possible treatment for certain patients with anemia caused by cancer treatment.

Now, NICE has updated the recommendations to expand the use of ESAs—epoetin alfa, beta, theta, and zeta, as well as darbepoetin alfa—to all other indications within their UK marketing authorizations.

“A lot of people with cancer having chemotherapy will become anemic,” noted Carole Longson, director of the Centre for Health Technology Evaluation at NICE.

“Managing anemia often requires extra trips to the hospital and can significantly affect a person’s quality of life. This updated final guidance recommends more options, epoetin and darbepoetin, that are both clinically and cost-effective and which also significantly improve quality of life for people who develop anemia whilst having cancer therapy.”

The 2008 NICE guidance recommended erythropoietin analogues with iron injections as a possible treatment for anemia caused by cancer treatment only in:

• Women receiving platinum-based chemotherapy for cancer of the ovaries who have a blood hemoglobin level of 8 g/100 mL or lower
• Patients who have very severe anemia and cannot receive blood transfusions.

NICE’s updated final guidance recommends using darbepoetin alfa and epoetin alfa, beta, theta, and zeta within their marketing authorizations as an option for treating anemia in cancer patients undergoing chemotherapy.

Epoetin alfa (Eprex, Janssen-Cilag, and Binocrit, Sandoz), and epoetin zeta (Retacrit, Hospira UK) have UK marketing authorization to treat anemia and to reduce transfusion requirements in adult patients receiving chemotherapy for solid tumors, malignant lymphoma, or multiple myeloma, who are at risk of transfusion as assessed by the patients’ general status (eg, cardiovascular status, pre-existing anemia at the start of chemotherapy).

Binocrit and Retacrit are both biosimilar medicines referenced to Eprex. Eprex, Binocrit, and Retacrit are available in pre-filled syringes at net prices of £5.53, £4.33, and £5.66 per 1000 units, respectively.

Epoetin beta (NeoRecormon, Roche Products) and epoetin theta (Eporatio, Teva UK) have UK marketing authorization to treat symptomatic anemia in adult patients with non-myeloid malignancies who are receiving chemotherapy.

NeoRecormon is available in a pre-filled syringe at a net price of £3.51 per 500 units, and Eporatio is available in a pre-filled syringe at a net price of £5.99 per 1000 units.

Darbepoetin alfa (Aranesp, Amgen) has UK marketing authorization to treat symptomatic anemia in adult cancer patients with non-myeloid malignancies who are receiving chemotherapy. Aranesp is available in a pre-filled syringe at a net price of £14.68 per 10 micrograms.

Costs (excluding value-added tax) may vary in different settings because of negotiated procurement discounts.

Cancer patient receiving

chemotherapy

Credit: Rhoda Baer

The UK’s National Institute for Health and Care Excellence (NICE) has updated its guidance to expand the use of erythropoiesis-stimulating agents (ESAs) in cancer patients.

In 2008, NICE issued a guidance recommending ESAs as a possible treatment for certain patients with anemia caused by cancer treatment.

Now, NICE has updated the recommendations to expand the use of ESAs—epoetin alfa, beta, theta, and zeta, as well as darbepoetin alfa—to all other indications within their UK marketing authorizations.

“A lot of people with cancer having chemotherapy will become anemic,” noted Carole Longson, director of the Centre for Health Technology Evaluation at NICE.

“Managing anemia often requires extra trips to the hospital and can significantly affect a person’s quality of life. This updated final guidance recommends more options, epoetin and darbepoetin, that are both clinically and cost-effective and which also significantly improve quality of life for people who develop anemia whilst having cancer therapy.”

The 2008 NICE guidance recommended erythropoietin analogues with iron injections as a possible treatment for anemia caused by cancer treatment only in:

• Women receiving platinum-based chemotherapy for cancer of the ovaries who have a blood hemoglobin level of 8 g/100 mL or lower
• Patients who have very severe anemia and cannot receive blood transfusions.

NICE’s updated final guidance recommends using darbepoetin alfa and epoetin alfa, beta, theta, and zeta within their marketing authorizations as an option for treating anemia in cancer patients undergoing chemotherapy.

Epoetin alfa (Eprex, Janssen-Cilag, and Binocrit, Sandoz), and epoetin zeta (Retacrit, Hospira UK) have UK marketing authorization to treat anemia and to reduce transfusion requirements in adult patients receiving chemotherapy for solid tumors, malignant lymphoma, or multiple myeloma, who are at risk of transfusion as assessed by the patients’ general status (eg, cardiovascular status, pre-existing anemia at the start of chemotherapy).

Binocrit and Retacrit are both biosimilar medicines referenced to Eprex. Eprex, Binocrit, and Retacrit are available in pre-filled syringes at net prices of £5.53, £4.33, and £5.66 per 1000 units, respectively.

Epoetin beta (NeoRecormon, Roche Products) and epoetin theta (Eporatio, Teva UK) have UK marketing authorization to treat symptomatic anemia in adult patients with non-myeloid malignancies who are receiving chemotherapy.

NeoRecormon is available in a pre-filled syringe at a net price of £3.51 per 500 units, and Eporatio is available in a pre-filled syringe at a net price of £5.99 per 1000 units.

Darbepoetin alfa (Aranesp, Amgen) has UK marketing authorization to treat symptomatic anemia in adult cancer patients with non-myeloid malignancies who are receiving chemotherapy. Aranesp is available in a pre-filled syringe at a net price of £14.68 per 10 micrograms.

Costs (excluding value-added tax) may vary in different settings because of negotiated procurement discounts.

Cancer patient receiving

chemotherapy

Credit: Rhoda Baer

The UK’s National Institute for Health and Care Excellence (NICE) has updated its guidance to expand the use of erythropoiesis-stimulating agents (ESAs) in cancer patients.

In 2008, NICE issued a guidance recommending ESAs as a possible treatment for certain patients with anemia caused by cancer treatment.

Now, NICE has updated the recommendations to expand the use of ESAs—epoetin alfa, beta, theta, and zeta, as well as darbepoetin alfa—to all other indications within their UK marketing authorizations.

“A lot of people with cancer having chemotherapy will become anemic,” noted Carole Longson, director of the Centre for Health Technology Evaluation at NICE.

“Managing anemia often requires extra trips to the hospital and can significantly affect a person’s quality of life. This updated final guidance recommends more options, epoetin and darbepoetin, that are both clinically and cost-effective and which also significantly improve quality of life for people who develop anemia whilst having cancer therapy.”

The 2008 NICE guidance recommended erythropoietin analogues with iron injections as a possible treatment for anemia caused by cancer treatment only in:

• Women receiving platinum-based chemotherapy for cancer of the ovaries who have a blood hemoglobin level of 8 g/100 mL or lower
• Patients who have very severe anemia and cannot receive blood transfusions.

NICE’s updated final guidance recommends using darbepoetin alfa and epoetin alfa, beta, theta, and zeta within their marketing authorizations as an option for treating anemia in cancer patients undergoing chemotherapy.

Epoetin alfa (Eprex, Janssen-Cilag, and Binocrit, Sandoz), and epoetin zeta (Retacrit, Hospira UK) have UK marketing authorization to treat anemia and to reduce transfusion requirements in adult patients receiving chemotherapy for solid tumors, malignant lymphoma, or multiple myeloma, who are at risk of transfusion as assessed by the patients’ general status (eg, cardiovascular status, pre-existing anemia at the start of chemotherapy).

Binocrit and Retacrit are both biosimilar medicines referenced to Eprex. Eprex, Binocrit, and Retacrit are available in pre-filled syringes at net prices of £5.53, £4.33, and £5.66 per 1000 units, respectively.

Epoetin beta (NeoRecormon, Roche Products) and epoetin theta (Eporatio, Teva UK) have UK marketing authorization to treat symptomatic anemia in adult patients with non-myeloid malignancies who are receiving chemotherapy.

NeoRecormon is available in a pre-filled syringe at a net price of £3.51 per 500 units, and Eporatio is available in a pre-filled syringe at a net price of £5.99 per 1000 units.

Darbepoetin alfa (Aranesp, Amgen) has UK marketing authorization to treat symptomatic anemia in adult cancer patients with non-myeloid malignancies who are receiving chemotherapy. Aranesp is available in a pre-filled syringe at a net price of £14.68 per 10 micrograms.

Costs (excluding value-added tax) may vary in different settings because of negotiated procurement discounts.

Daily rosuvastatin did not decrease fracture risk in a large international clinical trial involving older men and women who had elevated CRP levels, according to a report published online Dec. 1 in JAMA Internal Medicine.

Statins are thought to stimulate bone formation and increase bone mineral density, suggesting that they may exert clinical benefits beyond cardiovascular disease (CVD) prevention. Several observational studies have reported that statin users show a decreased risk of osteoporotic fractures, compared with nonusers. To examine this possible benefit, the JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial enrolled 17,802 men older than 50 years and women older than 60 years to receive either rosuvastatin or matching placebo and be followed for up to 5 years (median follow-up, 2 years) for both CVD and fracture events. The study was conducted at 1,315 medical centers in 26 countries, said Dr. Jessica M. Peña of the division of cardiology, Montefiore Medical Center, New York, and her associates.

A total of 431 participants sustained fractures: 221 in the rosuvastatin group and 210 in the placebo group, a nonsignificant difference. The corresponding rate of fracture was 1.20 per 100 person-years with the statin and 1.14 per 100 person-years with placebo, also a nonsignificant difference. The lack of protection associated with the active drug was consistent between men and women, across all fracture sites, and regardless of the participants’ fracture history. It also persisted through several sensitivity analyses, the investigators said (JAMA Intern. Med. 2014 Dec. 1 [doi:10.1001/jamainternmed.2014.6388]).

“Our study does not support the use of statins in doses used for cardiovascular disease prevention to reduce the risk of fracture,” the researchers noted.

Daily rosuvastatin did not decrease fracture risk in a large international clinical trial involving older men and women who had elevated CRP levels, according to a report published online Dec. 1 in JAMA Internal Medicine.

Statins are thought to stimulate bone formation and increase bone mineral density, suggesting that they may exert clinical benefits beyond cardiovascular disease (CVD) prevention. Several observational studies have reported that statin users show a decreased risk of osteoporotic fractures, compared with nonusers. To examine this possible benefit, the JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial enrolled 17,802 men older than 50 years and women older than 60 years to receive either rosuvastatin or matching placebo and be followed for up to 5 years (median follow-up, 2 years) for both CVD and fracture events. The study was conducted at 1,315 medical centers in 26 countries, said Dr. Jessica M. Peña of the division of cardiology, Montefiore Medical Center, New York, and her associates.

A total of 431 participants sustained fractures: 221 in the rosuvastatin group and 210 in the placebo group, a nonsignificant difference. The corresponding rate of fracture was 1.20 per 100 person-years with the statin and 1.14 per 100 person-years with placebo, also a nonsignificant difference. The lack of protection associated with the active drug was consistent between men and women, across all fracture sites, and regardless of the participants’ fracture history. It also persisted through several sensitivity analyses, the investigators said (JAMA Intern. Med. 2014 Dec. 1 [doi:10.1001/jamainternmed.2014.6388]).

“Our study does not support the use of statins in doses used for cardiovascular disease prevention to reduce the risk of fracture,” the researchers noted.

Daily rosuvastatin did not decrease fracture risk in a large international clinical trial involving older men and women who had elevated CRP levels, according to a report published online Dec. 1 in JAMA Internal Medicine.

Statins are thought to stimulate bone formation and increase bone mineral density, suggesting that they may exert clinical benefits beyond cardiovascular disease (CVD) prevention. Several observational studies have reported that statin users show a decreased risk of osteoporotic fractures, compared with nonusers. To examine this possible benefit, the JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial enrolled 17,802 men older than 50 years and women older than 60 years to receive either rosuvastatin or matching placebo and be followed for up to 5 years (median follow-up, 2 years) for both CVD and fracture events. The study was conducted at 1,315 medical centers in 26 countries, said Dr. Jessica M. Peña of the division of cardiology, Montefiore Medical Center, New York, and her associates.

A total of 431 participants sustained fractures: 221 in the rosuvastatin group and 210 in the placebo group, a nonsignificant difference. The corresponding rate of fracture was 1.20 per 100 person-years with the statin and 1.14 per 100 person-years with placebo, also a nonsignificant difference. The lack of protection associated with the active drug was consistent between men and women, across all fracture sites, and regardless of the participants’ fracture history. It also persisted through several sensitivity analyses, the investigators said (JAMA Intern. Med. 2014 Dec. 1 [doi:10.1001/jamainternmed.2014.6388]).

“Our study does not support the use of statins in doses used for cardiovascular disease prevention to reduce the risk of fracture,” the researchers noted.

Dr. Hickner’s editorial “EHRs: Something’s gotta give” (J Fam Pract. 2014;63:558) prompted me to reflect on the elements of electronic health records (EHRs) that cannot change and the ones that can.

The EHR system I use allows the EHR to serve as a 
quality recorder, and it appears 
this is the most important part,
 because the reminders of what
 needs to be documented come first and are color-coded. From a reimbursement point of view, what is important is not the narrative, but the expanded “elements” that make it a billing document. I believe this will not change.

What can change is how the note information is organized, and I think the organization should be different for specific roles. At intake, a medical assistant can review allergies, medication lists, and preventive services; update family history; and take vital signs and history of present illness (HPI). As the physician, I want the note to show the information in the order that I process it during the visit: 1) allergies/medication list, 2) concerns/complaints with brief documentation, 3) vitals, 4) physical, 5) assessment, and 6) plan.

After the note is signed off on, I want a different format for review purposes: 1) assessment/plan (because this is what I look at first for follow-up), 2) HPI/review of systems, 3) physical, 4) allergies, 5) medication list, 6) past medical history, and 7) quality reminders (if they show up at all after the visit is complete).

Is it asking too much for a programmer to make the EHR organize information in this manner?

Edward Friedler, MD
Annandale, Va

I still dictate my notes and they very much tell a story that an EHR cannot. I have been audited repeatedly and I always have all the bullet points and essentials that the insurance company wants, but this information is in a format that everyone—including patients—can read and appreciate.

The move to APSO (assessment, plan, subjective, objective) from SOAP (subjective, objective, assessment, plan) is an example of the tail wagging the dog. Rather than fix the note so the time-honored SOAP format works, we acknowledge that no one actually reads the long template notes and they want to get to the bottom line (ie, the assessment and plan).

My dream is to return to the days when we only listed the positive findings, the assumption being that a competent physician did the exam that was required and it’s unnecessary to state that the examined anatomy was normal. Unfortunately, so much of what we must do is driven by lawyers and insurance companies—not by doctors.

David M. Brill, DO
Rocky River, Ohio

I now take photos of all of the ludicrous choices our EHR tosses at me, such as “laceration of third eyelid” or “injury, crushed by falling aircraft due to terrorist.” Most of my EHR entries now say, “See scanned handwritten note for accuracy.”

The issue of EHRs needs to be kept on the front burner. It is destroying doctor/patient relationships and quality diagnostic care while hiding the important findings in the garbage.

Jay Hammett, MD
Knoxville, Tenn

I’m in a group practice of 10 family physicians and in a typical workday, each of us sees 23 to 25 patients, answers e-mails/phone calls, and reviews labs/studies, which leaves no time for anything else. There’s a constant struggle to stay on top of the quality of the notes. I have preserved the quality of my own notes by free typing. I free type a differential next to my assessment or on the first line of the plan. I don’t use templates; they slow me down too much.

Kelly Luba, DO
Phoenix, Ariz

I was a civil service physician working for the Department of the Navy in 2005 when EHRs were thrust upon me. The system was not particularly user-friendly. Free texting was highly discouraged and it was strongly preferred that we used structured text embedded in the program.

I couldn’t use the program as envisioned, so I found a work-around. I would paste the 4 sections of the SOAP note directly into the appropriate free text sections of the electronic record. My assessment included the correct diagnosis, and I would pick a general EHR diagnosis from the dropdown list. Visually, my records did not look any different from those of other health care providers who used structured text.

I used this method until my civil service retirement in 2014. All of my record peer reviews were outstanding, and I was told that my records were easy to understand. I finally let on to all that I never used structured text and that all of my records were really written the old-fashioned way. I still used a clipboard during the patient visit, and completed all records after the patient left.

David F. Scaccia, DO, MPH
Kittery, Maine

Dr. Hickner’s editorial “EHRs: Something’s gotta give” (J Fam Pract. 2014;63:558) prompted me to reflect on the elements of electronic health records (EHRs) that cannot change and the ones that can.

The EHR system I use allows the EHR to serve as a 
quality recorder, and it appears 
this is the most important part,
 because the reminders of what
 needs to be documented come first and are color-coded. From a reimbursement point of view, what is important is not the narrative, but the expanded “elements” that make it a billing document. I believe this will not change.

What can change is how the note information is organized, and I think the organization should be different for specific roles. At intake, a medical assistant can review allergies, medication lists, and preventive services; update family history; and take vital signs and history of present illness (HPI). As the physician, I want the note to show the information in the order that I process it during the visit: 1) allergies/medication list, 2) concerns/complaints with brief documentation, 3) vitals, 4) physical, 5) assessment, and 6) plan.

After the note is signed off on, I want a different format for review purposes: 1) assessment/plan (because this is what I look at first for follow-up), 2) HPI/review of systems, 3) physical, 4) allergies, 5) medication list, 6) past medical history, and 7) quality reminders (if they show up at all after the visit is complete).

Is it asking too much for a programmer to make the EHR organize information in this manner?

Edward Friedler, MD
Annandale, Va

I still dictate my notes and they very much tell a story that an EHR cannot. I have been audited repeatedly and I always have all the bullet points and essentials that the insurance company wants, but this information is in a format that everyone—including patients—can read and appreciate.

The move to APSO (assessment, plan, subjective, objective) from SOAP (subjective, objective, assessment, plan) is an example of the tail wagging the dog. Rather than fix the note so the time-honored SOAP format works, we acknowledge that no one actually reads the long template notes and they want to get to the bottom line (ie, the assessment and plan).

My dream is to return to the days when we only listed the positive findings, the assumption being that a competent physician did the exam that was required and it’s unnecessary to state that the examined anatomy was normal. Unfortunately, so much of what we must do is driven by lawyers and insurance companies—not by doctors.

David M. Brill, DO
Rocky River, Ohio

I now take photos of all of the ludicrous choices our EHR tosses at me, such as “laceration of third eyelid” or “injury, crushed by falling aircraft due to terrorist.” Most of my EHR entries now say, “See scanned handwritten note for accuracy.”

The issue of EHRs needs to be kept on the front burner. It is destroying doctor/patient relationships and quality diagnostic care while hiding the important findings in the garbage.

Jay Hammett, MD
Knoxville, Tenn

I’m in a group practice of 10 family physicians and in a typical workday, each of us sees 23 to 25 patients, answers e-mails/phone calls, and reviews labs/studies, which leaves no time for anything else. There’s a constant struggle to stay on top of the quality of the notes. I have preserved the quality of my own notes by free typing. I free type a differential next to my assessment or on the first line of the plan. I don’t use templates; they slow me down too much.

Kelly Luba, DO
Phoenix, Ariz

I was a civil service physician working for the Department of the Navy in 2005 when EHRs were thrust upon me. The system was not particularly user-friendly. Free texting was highly discouraged and it was strongly preferred that we used structured text embedded in the program.

I couldn’t use the program as envisioned, so I found a work-around. I would paste the 4 sections of the SOAP note directly into the appropriate free text sections of the electronic record. My assessment included the correct diagnosis, and I would pick a general EHR diagnosis from the dropdown list. Visually, my records did not look any different from those of other health care providers who used structured text.

I used this method until my civil service retirement in 2014. All of my record peer reviews were outstanding, and I was told that my records were easy to understand. I finally let on to all that I never used structured text and that all of my records were really written the old-fashioned way. I still used a clipboard during the patient visit, and completed all records after the patient left.

David F. Scaccia, DO, MPH
Kittery, Maine

Dr. Hickner’s editorial “EHRs: Something’s gotta give” (J Fam Pract. 2014;63:558) prompted me to reflect on the elements of electronic health records (EHRs) that cannot change and the ones that can.

The EHR system I use allows the EHR to serve as a 
quality recorder, and it appears 
this is the most important part,
 because the reminders of what
 needs to be documented come first and are color-coded. From a reimbursement point of view, what is important is not the narrative, but the expanded “elements” that make it a billing document. I believe this will not change.

What can change is how the note information is organized, and I think the organization should be different for specific roles. At intake, a medical assistant can review allergies, medication lists, and preventive services; update family history; and take vital signs and history of present illness (HPI). As the physician, I want the note to show the information in the order that I process it during the visit: 1) allergies/medication list, 2) concerns/complaints with brief documentation, 3) vitals, 4) physical, 5) assessment, and 6) plan.

After the note is signed off on, I want a different format for review purposes: 1) assessment/plan (because this is what I look at first for follow-up), 2) HPI/review of systems, 3) physical, 4) allergies, 5) medication list, 6) past medical history, and 7) quality reminders (if they show up at all after the visit is complete).

Is it asking too much for a programmer to make the EHR organize information in this manner?

Edward Friedler, MD
Annandale, Va

I still dictate my notes and they very much tell a story that an EHR cannot. I have been audited repeatedly and I always have all the bullet points and essentials that the insurance company wants, but this information is in a format that everyone—including patients—can read and appreciate.

The move to APSO (assessment, plan, subjective, objective) from SOAP (subjective, objective, assessment, plan) is an example of the tail wagging the dog. Rather than fix the note so the time-honored SOAP format works, we acknowledge that no one actually reads the long template notes and they want to get to the bottom line (ie, the assessment and plan).

My dream is to return to the days when we only listed the positive findings, the assumption being that a competent physician did the exam that was required and it’s unnecessary to state that the examined anatomy was normal. Unfortunately, so much of what we must do is driven by lawyers and insurance companies—not by doctors.

David M. Brill, DO
Rocky River, Ohio

I now take photos of all of the ludicrous choices our EHR tosses at me, such as “laceration of third eyelid” or “injury, crushed by falling aircraft due to terrorist.” Most of my EHR entries now say, “See scanned handwritten note for accuracy.”

The issue of EHRs needs to be kept on the front burner. It is destroying doctor/patient relationships and quality diagnostic care while hiding the important findings in the garbage.

Jay Hammett, MD
Knoxville, Tenn

I’m in a group practice of 10 family physicians and in a typical workday, each of us sees 23 to 25 patients, answers e-mails/phone calls, and reviews labs/studies, which leaves no time for anything else. There’s a constant struggle to stay on top of the quality of the notes. I have preserved the quality of my own notes by free typing. I free type a differential next to my assessment or on the first line of the plan. I don’t use templates; they slow me down too much.

Kelly Luba, DO
Phoenix, Ariz

I was a civil service physician working for the Department of the Navy in 2005 when EHRs were thrust upon me. The system was not particularly user-friendly. Free texting was highly discouraged and it was strongly preferred that we used structured text embedded in the program.

I couldn’t use the program as envisioned, so I found a work-around. I would paste the 4 sections of the SOAP note directly into the appropriate free text sections of the electronic record. My assessment included the correct diagnosis, and I would pick a general EHR diagnosis from the dropdown list. Visually, my records did not look any different from those of other health care providers who used structured text.

I used this method until my civil service retirement in 2014. All of my record peer reviews were outstanding, and I was told that my records were easy to understand. I finally let on to all that I never used structured text and that all of my records were really written the old-fashioned way. I still used a clipboard during the patient visit, and completed all records after the patient left.

David F. Scaccia, DO, MPH
Kittery, Maine