Arthritis related pain and safety concerns of NSAIDs

This month, the December 2012 issue of the Open Rheumatology Journal published an online article from a group that was brought together for a meeting in Aachen, Germany by Grünenthal GmbH, a pharmaceutical company.  The authors were compensated for their time and had assistance in the writing of the publication, which was funded by Grünenthal.

The article describes osteoarthritis and rheumatoid arthritis, as well as multiple therapies.  It concludes that the use of combinations of medications, as well as a multimechanistic approach are what is needed to help avoid the long-term potential safety concerns associated with NSAIDs. 

Inconsistency seen in safety labeling for generic drugs

An article published in  Pharmacoepidemiology and Drug Safety notes that over two-thirds of generic drugs in the U.S. have safety warning labels that differ from the equivalent brand-name medications.

According to the lead author, Jon Duke, "generic drug labels may contain incomplete or incorrect safety information."  This becomes problematic when the generic label is used by the physician to make prescribing decisions. If side effects, information on durg interactions or other safety issues are not in the label, then the patient may be at an increased risk for adverse events.

Out of more than 1,000 generic drugs, nearly 70% had some discrepancies in their safety labeling. Strikingly,  9% had differences of more than 10 side effects.

Androgen deprivation and prostate cancer

Saylor and Smith of the Massachusetts General Hospital Cancer Center in Boston, Massachusetts have an article that is coming out in the Journal of Urology in January 2013 which discusses adverse effects of androgen deprivation therapy (ADT).  Their review focuses on the more recently described metabolic complications of ADT including obesity, insulin resistance and lipid alterations as well as the association of androgen deprivation therapy with diabetes and cardiovascular disease.

They found that ADT causes a decrease in lean mass (muscle) and an increase in the mass of fat.  This was associated with a decrease in insulin sensitivity and increase in LDL, HDL and triglycerides.  This is associated with an increase in the incidence of diabetes and cardiovascular disease.

The benefit versus the risk of ADT must be considered when considering treatment, and it is recommended to screen for risk factors associated with diabetes and cardiovascular disease  and treat as indicated, thus mitigating the adverse effects that can be associated with ADT.

Mobile App for Oncology Adverse Events And Graft-Versus-Host Disease

Velos Aversi, an iPad app for clinicians in oncology and bone marrow transplantation has recently been released.

Velos Aversi is designed to record, track, and export patient adverse events (AE) and Graft-Versus-Host Disease (GVHD) at point-of-care in hospital and ambulatory care settings. With a few touches on the iPad, clinicians, physicians, and research nurses can review and manage their patients’ AE and GVHD histories anytime, anywhere—freeing them from large and cumbersome paper files. The app allows for more accurate attribution and reduces transcription errors that can occur when AE data entry is delayed. Direct and immediate input by clinicians saves time and ensures the quality of the record, particularly when grading events.

Antinausea Drug Withdrawn From US Market

The FDA announced that the 32 mg dose of Zofran (ondansetron), an anti-nausea medication, will no longer be marketed in the US due to the potential the risk of Torsades de pointes, a serious cardiac rhythm abnormality.  The event occurs when there is a prolongation in the QTc interval, an important part of the electrical activity of the heart.  Prolongation of the QTc can be fatal.  Information from the FDA can be found here.

Diet Drugs and Death

It has been known for quite awhile that drug-induced valvulopathy is an issue for fenfluramines (diet drugs).

Fenfluramine, which was sold as Pondimin, Ponderax and Adifax, was one part of a two drug combination sold as Fen-Phen for anti-obesity.  Fenfluramine was removed from the U.S. market in 1997 following reports of heart valve disease and pulmonary hypertension.    The other medication in the diet combination was phentermine.

Fenfluramine is a mixture of dextrofenfluramine and levofenfluramine (i.e. it's racemic mixture of two enantiomoers).  It causes an increase in the neurotransmitor serotonin.  Serotonin is known to be responsible for mood and appetite.  The increase in serotonin leads to the sensation of feeling full and not hungry.  It is postulated that fenfluramine, a sympathomimetic amine, causes release of serotonin and inhibits the reuptake of serotonin.  High levels of serotonin are found to decrease appetite in humans.

Fenfluramine, however, has "off-target" effects via activation of 5-hydroxytryptamine (5-HT) 2B receptor (5-HT2BR) expressed on heart valve leaflets.  This leads to a growth on the heart valves, leaving them structurally changed and incapable of closing properly.  Clinically, this can be detected by cardiovascular symptoms, which include a heart murmur, shortness of breath (dyspnea), edema, chest pain, congestive heart failure (CHF), palpitations, as well as supraventricular tachycardia. These symptoms are well described in the New England Journal of Medicine.

Macroscopic appearance: anterior leaflet 
of the mitral valve
 with thickened and retractile insertion 
of the chordae tendineae.

It is postulated that fenfluramine, a sympathomimetic amine, causes release of serotonin and inhibits the reuptake of serotonin.  As noted above, high levels of serotonin are found to decrease appetite in humans.  Elevated serotonin is also associated with acute or chronic pulmonary hypertension from pulmonary vasoconstriction or cardiac valve fibrosis (endocardial fibrosis) from overstimulation of serotonic growth receptors on fibrocytes.  Additionally increased serotonin levels are a factor in retroperitoneal fibrosis.

Serotonin is an intense pulmonary vasoconstrictor that stimulates proleferation of vascular smooth muscle by interacting synergistically with platelet-derived growth factor.

Why Did France Wait To Pull A Weight Loss Drug?

It took years for France to pull Mediator (benfluorex) from its market.  But why did it take so long for the French Regulatory Authority, Afssaps, to force Servier to remove it from the Market in 2009?  The drug was being used for weight loss.  It was developed by the French pharma company, Servier, and approved by Regulators 35 years ago.  The drug, however was said to have been the cause of death for 2000 people.

In 1999 there was an official report that Mediator could cause heart disease, yet it stayed on the French market  for an additional 10 years.  What could be the reason?

In 2000, according to Martine Verdier, an attorney representing victims, "there was a scientific study that demonstrated the side effects."  Valvular heart disease was the issue.  This is not the first time that there was an association between a medication being used for weight loss and valvular heart disease and associated pulmonary hypertension.  In fact, according to The New York Times there were two other Servier wight-loss medications, which were closely related to Mediator that were at the center of the infamous fen-phen scandal in the late 1990s in the United States.

Mediator (benfluorex) is an amphetamine derivative.  Fenfluramine and dexfenfluramine  are amphetamine derivatives and were licensed to companies in the US and then marketed by Wyeth as the drug combination for wight loss.  In September 1997 the FDA announced the withdrawal of fenfluramine and dexfenfluramine.  Dexfenfluramine was manufactured for Interneuron Pharmaceuticals and marketed under the name of Redux by Wyeth, which also manufactured  and marketed fenfluramine under the brand name Pondimin. Both companies  agreed to voluntarily withdraw their drugs.  Nevertheless, Mediator remained available to the French public.


Servier stands accused of misleading the public over the ingredients of the Mediator.  The French government has accused the company of consumer fraud and manslaughter.  After Servier was granted a market approval for Mediator as a diabetes drug, it promoted the drug as a prescription for weight loss.  This was done to increase the sales of the drug, unfortunately it also increased the number of patients harmed.

Following this scandal, the head of the French equivalent to the FDA known as Afssaps resigned.  France has since implemented reforms to Afssaps, which is now known as Ansm.  The new French National Agency of Medicine and Health Products Safety is hoped to revamp the French Regulatory Agency and establish new trust and confidence following the scandal over Mediator.

Electronic Medical Records and Patient Safety

Electronic medical record (EMR) systems and electronic health records (EHR) have been purported to reduce patient mortality, reduce medical errors, increase health care savings and improve health.  This appears, in part, to be a result of decreased medication errors that could result in adverse drug reactions (ADRs).  One benefit is that electronic prescribing helps to save lives.  Could it be that there is less of a problem in reading the physicians' poor hand writing?


A study published in the Journal of Political Economy stated that a 10% increase in the use of electronic records in hospitals would save 16 newborns for every 100,000 live births.  This would result in the saving of 6,400 infants per year in the US.


According to the Centers for Disease Control and Prevention, in 2011, 57% of office-based physicians had EMR systems.

Adoption of EMR/EHR systems by office-based physicians has increased

According to a 2009 Harvard School of Public Health press release, the most commonly cited barriers to adoption of these systems were found to be:

• inadequate capital for purchase (73%)

• concerns about maintenance costs (44%)

• resistance from physicians (36%)

• unclear return on investment (32%)

• lack of staff with adequate IT expertise (30%)

The press release was based on an article published in the New England Journal of Medicine.  The first author of the NEJM article gave an interview discuss EHR which can be viewed here.

Statin-Associated Muscular and Renal Adverse Events

Using the US Food and Drug Administration (FDA) adverse event reports (AERs) system, a group of investigators were able to review muscular and renal adverse events (AEs) reported with the use of statins.

There were 1,644,220 signals in AERs from 2004 to 2009 related to 4 statins.  The signals detected were myalgia, rhabdomyolysis and elevated creatine phosphokinase.  The investigators also noted that signals were seen for acute renal failure.

Guns versus Opioids: Which is deadlier?

In 2007 there were 12,632 gun related homicide deaths in the US according to the National Vital Statistics Reports from 2010.  This is less than the 14,800 Americans who died of opioid overdoses in 2008.  But the number of overdose related deaths is increasing:  The Centers for Disease Control and Prevention reported that 15,597 Americans died from opioid overdoses in 2009.

The FDA estimated that there were 22.9 million prescriptions for extended-release and long-acting opioids in 2011.  This raises concerns that the number of Americans who will continue to die will only increase.

Just like guns will probably always exist in America because it's a constitutional right, it is likely that the use of opioids will continue.

This month the FDA issued a safety measure to address the growing epidemic of opioid overdose.  Manufacturers of painkillers will now need to fund continuing educational programs for physicians and other healthcare providers.  This training will start in March 2013, but will be voluntary for healthcare providers.

The Obama administration's goal is to decrease abuse of prescription medications and the opioid overdoses leading to death by 15% in the next five years.  Not a lofty goal when one considers the increasing trend in deaths.

More than One in Four Medicare Beneficiaries Experience Some Degree of Harm While Hospitalized

This month the Office of Inspector General in the US Department of Health & Human Services has reported that more than one in four medicare beneficiaries experience some degree of harm while hospitalized.

Click here to see table in the report

The report noted that there were issues in the nation's hospital patient harm reporting system.

Findings included that half of States in the US had adverse event (AE) reporting systems in 2008, but only 12% of events met States requirements for reporting.

Of course, this means that half the States do not utilize a reporting system for AEs. This could be due in part to the fact that there are no Federal standards requiring States to have AE reporting systems.

Interestingly the report states that "hospital administrators indicated that staff often did not report events because they identified them not as patient harm, but rather as expected side effects."

Adverse Event Reporting of Lipitor, Lyrica, Viagra and Chantix

In May 2010, the FDA sent a letter to Pfizer's CEO, Jeffrey Kindler, warning the company that it had failed to report serious and unexpected adverse reactions to many of its widely known medications including Viagra (sildenafil), Lipitor (atorvastatin) and Lyrica (pregabalin) in a manner consistent with regulations.

The late reporting of adverse events was found to go back as far as 2004 and was noted to have increased over the six year period.  The FDA found that Pfizer did not report important cases within its 15-day period as a result of "misclassifying and/or downgrading reports to non-serious without reasonable justification."

In the past Pfizer had blamed issues with reporting on the lack of proper training of its employees with a new computerized adverse event reporting system.  Pfizer subsequently informed the FDA that this had been addressed, but the FDA called Pfizer's changes "inadequate" and "ineffective."  The FDA called for a revised "corrective action plan," also known as a CAP at the time.

A year later, in May 2011, the Institute for Safe Medication Practices (ISMP), a nonprofit organization, reported that "the risks of varenicline (CHANTIX) were underestimated in prior adverse event reporting." They outlined how Pfizer had failed to provide hundreds of reports through "the usual channels."  The ISMP noted that of the serious adverse event (SAE) reports, there were 150 patients who had completed suicides dating back to 2007.  As a result of the lapse in Pfizer's pharmacovigilance, more than half of the cases involving suicide were not sent to the FDA.  This meant that FDA analysts could not properly monitor this serious psychiatric issue.

Statins may help reduce bad memories

For a number of years there have been reports concerning the loss of memory, as well as muscle pains associated with the use of a group of medications called statins.  These drugs have been well known and widely prescribed to millions of people to help reduce cholesterol.  At least 32 million people in the US take these medications in the hopes that they will ward off a multitude of illnesses.  In the UK it is estimated that 5 million people take statins.

Cholesterol is associated with cardiovascular disease and can lead to myocardial infarctions, commonly called heart attacks.  Another risk associated with the build up of cholesterol in plaques is that of stroke.

In March of 2012 the U.S. Food and Drug Association (FDA) alerted the public that the entire class of statin drugs would be receiving new warnings in its labeling. The new label will warn that memory loss and confusion is associated with use of statins.  Additionally the labels will be updated to inform the public that statins can cause an increase in blood sugars called hyperglycemia and an increase in the risk of Type 2 diabetes.

With the above changes, the FDA is also removing its recommendation for routine and periodic monitoring of liver functioning.  Before patients start treatment with statins it is still recommended to get   liver enzyme tests (LFTs).

Cholesterol, however, is not all bad.  It is also not only from food; only 25% comes from diet.  The liver and other cells create approximately 75% of blood cholesterol.  There is good cholesterol, which is HDL and then bad cholesterol, also known as LDL.

Cholesterol is an important substance for normal functioning in the body.  Some people, however, have an increased risk of elevated cholesterol associated with genes that are inherited.  Others may have the ability to moderate their cholesterol through diet and exercise.

According to some investigators, a large number of patients do not achieve the desired goal of reduction in cholesterol levels after six months of treatment.

FDA Gives Alert That Ampyra Has Seizure Risk for Multiple Sclerosis Patients

Today, July 23, 2012, the FDA warned that there is a risk of seizures in patients with multiple sclerosis (MS) who start treatment with Ampyra (dalfampridine).

This is based on data that the FDA reviewed from post-marketing reports.  Most of the seizures reported took place within days to weeks after patients with MS started Ampyra at the recommended dose.  The patients did not have a history of previous seizures.

The FDA also updated the drug label for Ampyra to clarify rcommendations that kidney function should be monitored in individuals before they begin treatment with Ampyra.  Patients should be monitored at least once a year.

More information can be found on the FDA website.

It's not all bad news!

North Fulton Hospital in Atlanta Georgia has been given an "A" Hospital Safety Score by The Leapfrog Group, which is an independent, national nonprofit leader and advocate in hospital transparency. 

The Hospital Safety Score was calculated based on the guidance of The Leapfrog Group's Blue Ribbon Expert Panel using publicly available data regarding patient injuries, medical and medication errors, as well as infections. Hospitals are assigned an A, B, C, D, or F for their safety.

"Patient safety and quality are central to everything we do at North Fulton Hospital," said Deborah C. Keel, CEO of the hospital. "The Leapfrog Group's recognition publicly acknowledges the commitment of both medical staff and all hospital staff who 'blow the whistle' for patient safety each and every day."


Jennifer Green won a patient safety award for her as an infection preventionist and safety practitoner at Fort Hamilton Hospital in Cincinnati.  This award is given to those individuals who exemplify dedication and commitment to patient safety, work to communicate the importance of patient safety as an organizational priority and who serve as an outstanding role model to those other people working to further the safety of patients everywhere.

OxyContin formula change has many abusers switching to heroin

Researchers at the Washington University in St. Louis have found that the frequently abused prescription medication, OxyContin, is now leading drug abusers to switch from OxyContin to heroin as a result of a recent change in the drug's formulation.  An abuse-deterrent formulation was introduced in August 2010.  The researchers at Washington University examined the effect of the change in formulation with regard to the abuse of OxyContin and other opioids.

The painkiller's new formula makes inhaling or injecting the drug more difficult. This has led to a switch to heroin.  So while the abuse of OxyContin has decreased, which is good, the problem is that there is now a surge in the use of heroin.  This may lead to an increase in heroin related overdoses and other public health and safety issues associated with the street drug.

The Washington University scientists published their findings in the New England Journal of Medicine:

Cicero TJ, Ellis MS, Surrat HL. Effect of abuse-deterrent formulation of OxyContin.  The New England Journal of Medicine, July 12, 2012.

Effect of a Pharmacist Intervention on Clinically Important Medication Errors After Hospital Discharge: A Randomized Trial

This article from the Ann Intern Med. 3 July 2012;157(1):1-10 shows that half of all cardiac patients had clinically important medication errors after having an explanation of their medications and how to take them by a pharmacist.  Could it be that the patient wasn't able to process the information after having been hospitalized with a heart condition?

Clinical trial considerations on male contraception and collection of pregnancy information from female partners

Please find a recently published article by me and several of my colleagues related to the need for male contraception in clinical trials.  These considerations are also applicable to other settings outside of clinical trials.

There is little guidance regarding the risk of exposure of pregnant women/ women of childbearing potential to genotoxic or teratogenic compounds via vaginal dose delivered through seminal fluid during sexual intercourse.

These recommendations, based on a precaution principle, provide a consistent approach for minimizing the risk of embryo-fetal exposure to potentially harmful drugs during pregnancy of female partners of males in clinical trials. Proactive targeted collection of pregnancy information from female partners should help determine the teratogenic potential of a drug and minimize background noise and ethical/logistical issues.

Medical errors cause up to 98,000 deaths and more than 1 million injuries each year in the United States

Dr. Christopher Landrigan

In 1999 a report from the Institute of Medicine stated that medical errors cause up to 98,000 deaths and more than 1 million injuries each year in the United States.  There was a major response from a number of concerned groups to improve patient safety.  Some initiatives have been demonstrated to have a positive effect.  Others have not been evaluated rigorously or have not been implemented on a wide scale.


A "Special Article" in the New England Journal of Medicine by Christopher Landrigan, et al. eloquently notes that not much improvement has actually occurred.  The article, "Temporal Trends in Rates of Patient Harm Resulting from Medical Care" is a must read for those concerned about patient safety.  Soon after it's publication, Denise Grady of the New York Times wrote an article based on the study by Dr. Landrigan.


In the decade that passed since the report from the Institute of Medicine, only 17% of hospitals have computerized systems for ordering prescriptions, which is a source of medication errors.

Regulators Probe Roche's Drug-Safety Reporting

Severin Schwan, Roche CEO 

The European Medicines Agency (EMA), which is Europe's drug regulatory authority has stated that it will investigate Roche Holding AG after it found that Roche had failed to properly evaluate approximately 80,000 cases.  Patient deaths were reported in  15,161 of these cases.

Roche has indicated that it did not comply with regulations for the reporting of safety events.  Roche stated that "the company is working closely with health authorities, including the European Medicines Agency, to implement these measures in due time."

Adverse drug reactions leading children to the Emergency Department

The aim of the study was to determine the incidence of adverse drug reactions (ADR) that led children to hospital emergency care in a university hospital in São Paulo, SP. Medical charts (MC) of patients seen at the pediatric emergency department were selected according to International Classification of Diseases (ICD) codes consistent with ADR. Of 23,286 cases studied, 2,409 records were selected. An ADR was observed in 83 (0.36%) MC. Most ADR occurred in children aged 1-5 years with a slight predominance in males (51.8%). The drugs most commonly involved were antibiotics for systemic use (53.0%), vaccines (9.6%) and analgesics (7.2%). Most ADR were dermatological (54.2%) or gastrointestinal (22.9%) manifestations. Two ADR were considered severe (2.4%) while 61.4% were mild and 36.1% were moderate. The incidence was lower than in the literature, probably because it is a retrospective study that used the ICD for selecting the data assessed. The characteristics of ADR are similar to those found in other countries. Interventions are needed to improve the diagnosis and the use of antibiotics, as they were the drugs most involved in the ADR observed. Research in hospital emergency is important to acknowledge ADR that occur outside the hospital setting and may help to identify the most severe ones. Despite limitations, the method requires few resources and materials, and is a good alternative to initial diagnosis. The present study should be followed by studies with higher sensitivity to detect these reactions in order to propose prevention measures.

Incidence of adverse events and negligence in hospitalized patients: results of the Harvard Medical Practice Study I*

Here's an abstract of an interesting article, which first appeared in the New England Journal of Medicine and was subsequently republished:

Background: 

As part of an interdisciplinary study of medical injury and malpractice litigation, we estimated the incidence of adverse events, defined as injuries caused by medical management, and of the subgroup of such injuries that resulted from negligent or substandard care.

Methods: We reviewed 30 121 randomly selected records from 51 randomly selected acute care, nonpsychiatric hospitals in New York State in 1984. We then developed population estimates of injuries and computed rates according to the age and sex of the patients as well as the specialties of the physicians.

Results:  

Adverse events occurred in 3.7% of the hospitalizations (95% confidence interval 3.2 to 4.2), and 27.6% of the adverse events were due to negligence (95% confidence interval 22.5 to 32.6). Although 70.5% of the adverse events gave rise to disability lasting less than 6 months, 2.6% caused permanently disabling injuries and 13.6% led to death. The percentage of adverse events attributable to negligence increased in the categories of more severe injuries (Wald test x2 = 21.04, p,0.0001). Using weighted totals we estimated that among the 2 671 863 patients discharged from New York hospitals in 1984 there

were 98 609 adverse events and 27 179 adverse events involving negligence. Rates of adverse events rose with age (p,0.0001). The percentage of adverse events due to negligence was markedly higher among the elderly (p,0.01). There were significant differences in rates of adverse events among categories of clinical specialties (p,0.0001), but no differences in the percentage due to negligence.

Conclusions: There is a substantial amount of injury to patients from medical management, and many injuries are the result of substandard care.

Patient safety education for undergraduate medical students

The authors of an article published in BMC Medical Education conducted a survey of the medical literature related to patient safety education in the medical curriculum of medical schools.


The article notes that there are only a few relevant published studies on the inclusion of patient safety education in the undergraduate curriculum in medical schools either as a selective course, a lecture program, or by being integrated into the existing curriculum.  The search included developed countries with advanced health and education systems. 


It is clear that the integration of patient safety education into the existing curriculum in medical schools internationally, provides significant challenges and needs.

Medical students benefit from learning about patient safety in an interprofessional team

An article published in Medical Education by 

Elizabeth Anderson, 

Lucy Thorpe, 

David Heney and 

Stewart Petersen describes how d

elivering patient safety education interprofessionally heightens students’ awareness of the importance of effective team-working for safe care and care delivery.  This is not something that is routinely taught in either medical schools or in post-graduate training programs.  The authors conclude that designing a a workshop on team-based patient safety towards the end of medical education can enable students to assimilate all aspects of their curriculum relevant to safety. Students learn that there is a link between team factors and safety and this is increased when students learn interprofessionally.

Medical Errors Go Unreported 86% Of The Time

According to a recently released report from the Office of the Inspector General at the U.S. Department of Health and Human Services, medical errors go unreported in 86% of Medicare cases. US hospitals included in the study have incident reporting systems which are designed to capture such events.  Thirty four of the hospitals in the study noted that they "rely heavily" on the systems to find problems and make changes to improve patient safety.

http://oig.hhs.gov/oei/reports/oei-06-09-00091.pdf

New Warnings for Aliskiren & FDA / Novartis to Pull Valturna

The FDA issued new warnings about antihypertensive medications which contain aliskiren (Tekturna, Amturnide, Takamio, and Valturna) when used in combination with ACE inhibitors or angiotensin receptor blockers (ARBs). The FDA indicates that the drug combinations are contraindicated in patients with diabetes, and it is adding a new warning to avoid the use of this combination in patients with moderate to severe renal impairment (GFR <60 mL/min).

Novartis has announced it will pull Valturna from the U.S. market.  Valturna contains aliskiren (Tekturna^®) as one of its ingredients.

New EU Pharmacovigilance Legislation and Signal Detection

The new European Union Pharmacovigilance legislation was published in December 2010 and regulations go into effect in early July 2012.  A number of significant changes will take place.  The Regulations and Directives are legally binding.

One of the major changes is found in signal detection.  Industry will now need to have specific measures in place that document the process of signal detection.  Issues that need to be considered are the frequency of monitoring data, prioritization of signals...and a documented process.

This change has potential advantages and disadvantages.  Capturing and identifying signals in a timely fashion is essential.  The benefit to early detection of an Adverse Drug Reaction (ADR) is the possibility of improving patient safety.  ADR determination is based on a number of pharmacological and medical considerations.  Sometimes an ADR determination is made after a number of events are detected.  For serious and rare ADRs it is reasonable to make a determination with fewer events; one event may be enough to make an ADR association between the drug and the adverse reaction.

Considering the Benefit : Risk ratio or profile is quite important.  As in many of life's situations there are associated benefits and risks to any medical intervention.  Before starting a treatment or having a procedure these need to be taken into consideration.  The same holds true during the development of a product; the pros and cons must be weighed during this period as well as into the later stages of the product's lifecycle.  Patients who are on a treatment or who have received a medical device need to understand the potential impact of the detection of a signal that is related to their treatment or medical device in order to make an informed decision regarding choices that they may make in their healthcare.

For some people the benefit will be of greater importance than a possible risk.  Others will not want to take on the risk associated with a particular treatment.

Update on Breast Implants

Poly Implant Prothèse (PIP), a French medical devices manufacturer  produced breast implants   from 1991 to 2011.  The company utilized silicone in its implants.  In 2000 the US FDA launched a moratorium on silicone implants.  Some reports indicate that PIP introduced the use of industrial-grade silicone in 2001 in some of their products rather than approved medical-grade silicone.  Other sources say that the change in grade of implant may have occurred as early as 1997.

French surgeons began reporting a significant increase in the rupture rate of the implants in 2009.  This led to legal action against PIP and ultimately the company went bankrupt.

In December 2011, following the death of a female patient in France from Anaplastic Large-Cell Lymphoma (ALCL), which has an increased incidence in women with silicone breast implants, the French government recommended that the PIP implants with the industrial-grade silicone be removed from 30,000 women in France.

The company also made male chest, testicle and buttock implants.  The majority of these implants were exported to Latin America.

In the United Kingdom, it is estimated that 47,000 British women have received PIP breast implants.  The Medicines and Healthcare products Regulatory Agency (MHRA), which is England's agency responsible for enhancing and safeguarding the health of the public by ensuring that medicines and medical devices work and are acceptably safe, advises that there is no evidence to recommend routine removal of the implants.  Nevertheless, there is concern amongst women who have the PIP breast implants, plastic surgeons and other physicians.  The National Health Service (NHS) has stated that the private firms that placed the implants would remove them without charge.  The NHS  also said that any woman who is not given help by a private facility could visit their General Practitioner and have access to NHS services.

Outsourcing Pharmacovigilance

Not long ago many within Pharma thought that Drug Safety was an evil, unnecessary cost center. Over time the perception has changed and it's now recognized that Pharmacovigilance is an important function which is essential to protect the patient, public and product. Nevertheless, budget restraints and the rising costs of maintaining a professional workforce have led many across the industry to consider outsourcing. There's yet another reason for outsourcing: The shear volume of data coming in which needs to be collected at call centers, entered into databases, queried, cleaned, analyzed and reported makes this a task that must be shared round the clock and globe.

Reporting a Reaction to a Drug in the EU

In the European Union (EU), patients do not report directly to the Regulatory Authorities. The EU agency that is responsible for Drug Safety (Pharmacovigilance) is the European Medicines Agency (EMA), similar to the US Food and Drug Administration (FDA). Patients in the EU should report side effects to a medicine by informing their doctor or pharmacist. According to the EMA, these health care professionals can help put the information into the right medical context for further evaluation by the authorities, particularly if they suspect a serious or severe reaction. The EMA's goal is evaluate each case and when indicated take action, which

will involve warnings to the public and the medical community aimed at ensuring the safe use of a medicine and the prevention of future side effects. In extreme situations and, when justified, medicines have been removed from the market in order to protect public health. This is when the balance of risks outweighs benefits of the particular medicine. The EMA maintains a very informative website www.eudravigilance.ema.europa.eu

The Campaign for Modern Medicines

Eli Lilly and Company, a large US based pharmaceutical company, has created a website at modernmedicines, which is geared to providing information related to a petition that they have created to inform Congress that The Prescription Drug User Fee Act (PDUFA) needs to be "cleaned." The objective of the website and petition is “that patients deserve timely access to lifesaving medicines and that the U.S. must remain the global leader in discovering and delivering these breakthrough cures and treatments." They are asking public citizens to stand with the Campaign for Modern Medicines and urge Congress to pass PDUFA by July 4th free of extraneous additions that bring new costs and burdens to the FDA.”

The Benefits of Drug Safety in Early Stage Drug Development

I am presenting a talk on "The Benefits of Drug Safety in Early Stage Drug Development" at the upcoming Early Stage Clinical Development conference in Boston, MA on May 29, 2012. Information about this event can be found at the following LINK.

Learn About Pharmacovigilance

Drug Safety or Pharmacovigilance is an important endeavor that helps to protect patients and the public health. There are agencies throughout the world that have been set for this purpose. Additionally, pharmaceutical companies conduct activities on an ongoing basis to assure that patients and the public are protected and that medicines are being used safely and effectively. A variety of courses are given throughout many locations that help to educate individuals who are responsible for Pharmacovigilance. In April 2012 there was a meeting in Boston, MA "World Drug Safety Congress Americas" that provided a venue for learning and discussing a wide range of relevant topics concerning patient safety and new regulations that will have a major impact on how Pharmacovigilance are conducted. I was one of the speakers at this event and reviewed "The Key Clinical Safety Challenges: Signal Detection and Analyzing Safety Data Efficiently and Effectively." Information about the meeting can be found on the World Drug Safety Congress link here.

Reporting A Safety Issue in the US

The U.S. Food and Drug Administration (FDA) is the agency that is accountable for protecting and promoting public heath in the United States. It does this by setting regulations, conducting inspections and analyzing adverse events (AEs). The FDA maintains a computerized database where information related to AEs is stored and then analyzed. This database is called the Adverse Event Reporting System (AERS). The FDA monitors the AEs in the database to determine if there are signals that could represent a health risk to the patients and public. The reporting of AEs is done on a voluntary basis by healthcare providers, patients and the public. Manufacturers of medications are required to report information related to AEs that they become aware of either through the conduct of clinical trials or that occur spontaneously in patients taking medicines that are marketed by the company. Reporting of Adverse Events can be done as follows: Consumers and Healthcare Providers can report Adverse Events online or using a form available through the FDA by clicking here or pasting the following URL into their web browser: https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm

Drug Safety

Drug Safety is also known as Pharmacovigilance (PV). The World Health Organization (WHO) has defined PV as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem. WHO established its Programme for International Drug Monitoring in response to the thalidomide disaster detected in 1961. Together with the WHO Collaborating Centre for International Drug Monitoring, Uppsala, WHO promotes PV at the country level. At the end of 2010, 134 countries were part of the WHO PV Programme. The aims of PV are to enhance patient care and patient safety in relation to the use of medicines; and to support public health programmes by providing reliable, balanced information for the effective assessment of the risk-benefit profile of medicines.