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VOLUME 3 • ISSUE 1 • FALL 05 MDAdvantage Insurance Company of New Jersey Navigating Drug Safety Issues: The Physician’s Perspective By Robert B. Goley and Janet S. Puro Every day, there seems to be another drug or medical device in the news with safety issues. Popular antidepressants might increase the risk of teen suicide. Widely prescribed arthritis painkillers like Vioxx and Celebrex appear to be linked to heart attacks and strokes. The list goes on and on (see insert for a list of some of the most recent drug-related safety concerns). Many of these are drugs that you as a physician may be currently prescribing, or even taking yourself. The situation has left patients confused, drug companies defensive, and government officials at odds over how to fix the problem. tions. What should you be telling your patients? Do you face any liability in prescribing these drugs? This article, and its conclusion (set to appear in next quarter’s MDAdvisor), will set out to explore these issues. Surely, even the safest and most effective drugs we use can have serious side effects. Researchers will not know everything about even the best researched drug before it goes to market. But how do we know when the risk to patients is too high? Who bears the ultimate responsibility for the decision? Understanding the Role of the FDA The Food and Drug Administration (FDA) approves every drug that is sold in the United States. If the FDA determines through review of research and testing information that a particular drug is harmful or substandard, the manufacturer is notified and asked to remove the drug from the market, either temporarily (drug recall) or completely (drug withdrawal). A drug recall is mainly requested if there is an error in the medication, including contaminations, mislabeling, and dosage errors. A drug withdrawal is issued if a multitude of serious side effects or deaths are reported directly from patients taking the medication. Most companies will voluntarily remove their product from the market if flaws are detected. However, unless the Secretary of the Department of Health and Human Services declares an imminent health risk, the FDA cannot force a drugmaker to pull its medicine off the market. And where do you as a physician fit in to all of this confusion? With pharmaceutical companies advertising their products directly to consumers, patients are coming in to physician practices requesting, and even demanding, specific medica- In the early 1990s, at the height of the AIDS epidemic, the FDA was criticized for being too slow about approving potentially life-saving medicines. Now, the FDA is being criticized for allowing drugs on the market too quickly without focusing enough on whether the benefits of new drugs truly outweigh their risks. The Navigating Drug Safety Issues: The Physician’s Perspective (cont’d) FDA has also been criticized because many more resources are focused on approving new drugs than monitoring the safety of drugs already on the market. Categories of Drug Recall: Class I Dangerous/defective products that imply possible health problems Class II Implies temporary health problems and less serious threats Class III Products unlikely to cause problems, but do not comply with FDA standards This year, the FDA unveiled a new vision that will promote a culture of openness and enhanced oversight within the agency. As part of this vision, a new independent Drug Safety Oversight Board was created to oversee the management of drug safety issues, and will provide emerging information to health providers and patients about the risks and benefits of medicines. The Drug Safety Oversight Board held its inaugural meeting on June 17, 20051. Summaries of each board meeting will be posted at www.fda.gov approximately one week after each meeting. The most recent chapter in the FDA’s crisis culminated in the resignation of its Commissioner, Lester Crawford, on September 23, 2005. Increasing criticism and a particularly rocky final twelve months marked his three-year tenure at the FDA. So far, no candidate has publicly surfaced as a permanent replacement for Crawford, and any nominee will likely face tough Senate scrutiny. President Bush designated the National Cancer Institute’s director, Dr. Andrew von Eschenbach, to be the FDA’s acting commissioner in the interim. Do Physicians Receive Enough Information About Drug Safety? Despite the efforts of the FDA to ensure the safety of prescription drugs and oversee the information provided to physicians, there continues to be much information about drug studies that goes undisclosed. While often too complex for patients to understand, clinical trial results are useful to doctors and academic scientists, who use them to compare drugs and look for clues to possible side effects. However, companies are not required to disclose trial results to scientists or the public. Calls for disclosure continue to grow stronger with reports that drug manufacturers have failed to publish important patient safety data. Last year, the drug industry came under fire for failing to disclose poor antidepressant study results. Then in August 2004, GlaxoSmithKline agreed to pay $2.5 million to settle a suit by Eliot Spitzer, the New York Attorney General, alleging that Glaxo had hidden results from trials showing that its antidepressant Paxil might increase suicidal thoughts in children and teenagers2. Merck withdrew Vioxx from the market in September of 2004 because a study had found that the medicine doubled the risks of heart attacks and strokes. In the weeks after the announcement, Pfizer insisted that it had no evidence that its very similar drugs, Celebrex and Bextra, caused heart problems. Pfizer has since disclosed that it had, at the time of those statements, studies that indeed demonstrated heart problems among patients taking Celebrex or Bextra. In December 2004, the National Institutes of Health announced that a very large trial had found that high doses of Celebrex more than tripled the risk of heart problems3. As a result of these investigations, major drug makers have promised to provide more information about their research on new medicines, yet crucial facts about many clinical trials remain hidden. Within the drug industry, companies are sharply divided about how much information to reveal, both about new studies and completed studies for drugs already on the market. Pharmaceutical companies can hide negative trial results 888-355-5551 • www.MDAdvantageonline.com by refusing to publish studies, or by highlighting the most favorable data from studies they do publish. In recent years, journal editors and academic scientists have pressed big drug makers to release more information. Eli Lilly and some other companies have posted hundreds of trial results to a registry on the Web (www.clinicaltrials.gov). The registry is designed in part to prevent companies from conducting several trials of a drug, then publicizing only those trials with positive results. But other drug makers, including Merck, Pfizer, and GlaxoSmithKline, file only vague descriptions of many studies, often failing even to name the drugs under investigation. Drug names are helpful in tracking how many times a drug has been studied. Merck, Pfizer and Glaxo hold that disclosing too much information about early-stage trials might reveal business or scientific secrets4. As a result, doctors and patients lack critical information about important drugs. Understanding The Legal Environment We have all read many news reports in the past year of lawsuits brought against pharmaceutical companies for drug-related patient issues. In order to understand one’s own potential liability as a physician, it is necessary to understand the legal environment for pharmaceutical companies. There are two main types of suits brought against pharmaceutical companies: mass tort suits and class action suits. of duplicative and inconsistent rulings, orders or judgments, coordinates discovery, and promotes efficient utilization of judicial resources. Although there is centralized pretrial management, the cases will be tried individually or in groups. In cases filed in New Jersey Superior Court as part of a mass tort, claimants typically filed individual complaints. Although product manufacturers are most often the primary defendants, in the past, treating physicians prescribing or using the products have sometimes been named in the suit as direct defendants or, more rarely, brought into the suit as defendants in third party claims filed against them by other defendants. The Chief Justice of New Jersey has assigned four Superior Court Judges to exclusively manage mass tort cases. The cases are centralized and managed in three vicinages: the Civil Division Part in Middlesex, Atlantic and Bergen Counties. The County managing the mass tort maintains a master docket number, which consolidates and centralizes management of the claims. Each claimant may have separate counsel or more than one counsel. Each counsel may represent more than one claimant. A claimant can be an individual, group or corporation. Out-of-state attorneys may be admitted pro hac vice, which means they may be granted special permission to participate in a particular case, even though they are not licensed to practice in that state. Mass tort suits are different than personal injury claims related to acts of medical negligence or medical malpractice affecting an individual patient. They involve a large number of claims associated with a single product, device or catastrophic event. Regardless of the number of claimants, there is a “commonality” of facts and recurrent issues of law. Synergy or interdependence between the claims generally adds to their value. Currently, there are five mass torts centralized in NJ related to pharmaceutical products: Accutane, Diet Drugs (such as PhenFen with settlement agreements currently pending), HRT (Hormone Replacement Therapy) PPA (Phenylpropanolamine) and Vioxx. Currently an application is also pending to designate Bextra as a mass tort. To receive a designation of mass tort, an assignment judge of any vicinage (or an attorney involved in one or more of the cases) can apply to the New Jersey Supreme Court if the appropriate “commonality” criteria are met to warrant centralized case management. Centralized case management avoids the risk Class Action lawsuits are initiated when one or more parties file a complaint on behalf of themselves and all other people who may have a similar claim. When all of the legal prerequisites to a class action are met and the Court designates Class Certification, the suit covers all members as claimants of a particular group. ➢ Navigating Drug Safety Issues: The Physician’s Perspective (cont’d) By their very nature, however, tort suits for personal injury claims are often considered by the court as inappropriate for handling as a class action. Although the members of the proposed class may all allege that their various claims arose as the result of the same product, the court may conclude that each plaintiff’s damages must be determined on an individual basis. In such cases, a sufficient community of interest is lacking, and some courts have held that a class action is therefore not available. The basic requirements for class certification are “numerosity, commonality, typicality and predominance.” In situations involving class actions against a pharmaceutical company over a particular drug (for example), “class certification” covers all individuals who were prescribed the drug – even if the individuals have not brought suit themselves. All members of a “class” are included in an ultimate jury award or settlement – unless individuals previously decided to opt out of the suit. Class action suits may be filed in state or federal court. Suits covering plaintiffs residing in multiple states can be filed in any of the state courts with jurisdiction over some of the plaintiffs. When a high profile or newsworthy event occurs regarding a pharmaceutical product or a medical device, typically more than one class action suit or mass tort will be initiated – and the number of suits pending against just one drug can be huge. Plaintiff attorneys throughout the country often file actions against manufacturers in multiple venues based on identical issues and overlapping classes of claimants. For example, there are an estimated 5,000 suits pending against Merck in association with the drug Vioxx5. Laws governing class actions were intended to permit fair and efficient resolution of legitimate claims of numerous parties by allowing the claims to be aggregated into a single action against a defendant who has allegedly caused harm. However, there have been significant issues and problems with class action suits in the recent past, including instances where class members have been unfairly harmed or received little benefit for being members of the class, instances where counsel for the class were awarded excessively large fees, and instances where bias was shown against out-of-state defendants. In an attempt to improve the class action process and achieve greater procedural uniformity, President Bush signed the Class Action Fairness Act (“CAFA”) into law on February 18, 2005. CAFA is intended to overcome venue shopping, based on the perception that some state courts are more “class action friendly,” leading plaintiff attorneys to file cases in sympathetic jurisdictions. It also contains a Consumer Class Action Bill of Rights that is intended to curb “coupon settlements,” simplify explanations of rulings and settlements, and control fees collected by attorneys acting as class counsel6. This new law is not retroactive and therefore does not apply to class action suits currently pending. (The act applies to any civil action commenced on or after February 18, 2005). Going forward however, CAFA will in effect transfer many major class action suits from state courts to federal court. The Act provides federal district courts with jurisdiction over any class action in which the dispute exceeds $5 million (class members’ claims may be aggregated to meet or total that amount and the class must have a minimum of 100 members). If less than one-third of the members are from the primary defendant’s state, then federal jurisdiction will prevail. When greater than one-third but less than two-thirds of the members and the primary defendants are from a single state, the district courts have the option of declining jurisdiction and remanding the case to the state courts. If, however, greater than two-thirds of the class members and at least one of the primary defendants are all from a single state, and the principal injuries occurred in that state, then jurisdiction remains with the state and not the federal court. The Class Action Fairness Act will allow redundant state court actions to be removed to federal court, from which they can be transferred and consolidated by the Judicial Panel for Multidistrict Litigation (“MDL”). The Panel (created by an act of Congress in 1968) consists of seven federal judges (appointed by the Chief Justice of the United States). The panel determines if civil actions pending in different federal districts involve one or more common questions of fact to warrant transfer to one federal district for coordinated or consolidated management. The centralization process efficiently avoids duplication of discovery, prevents inconsistent pretrial rulings, and conserves resources of the parties, their counsel and the judiciary. Following completion of the centralized pretrial management, the Panel usually remands the cases back to their originating districts for trial. The MDL Panel has also remained involved in mass tort settlement programs as well. Examples of federal suits that have been reviewed by the MDL Panel in the past include fen/phen diet drugs and hormone replacement therapy. Currently there are multiple medical products liability suits pending review with the Panel, including Orthopedic Screw Products, Gammagard (IV Immunoglobulin), Diet Drugs, Rezulin Products (settlement program), Propulsid (settlement program), Silzone heart valve coating (settlement program), Sulzer Hip Prosthesis (settlement program), PPA (settlement program), Baycol (settlement program), Meridia, Paxil, Zyprexa, Ephedra, Accutane, and Vioxx. Will the CAFA accomplish what was intended? There is still some concern over the impact of large class action suits with claimants from multiple states being forced into federal court. There is also the potential that courts 888-355-5551 • www.MDAdvantageonline.com Honor Your Profession By Honoring Your Peers CAFA also specifies a “mass action” category, which is different than class certification. Mass actions are any civil action in which the claims of 100 or more persons are proposed to be tried jointly due to common questions of fact or law. Only those individuals who are claimants in the mass action suit are included in a final settlement or jury award. Under the new law, mass actions in state courts are subject to consolidation in federal court following the same rules as the certified class. MDAdvantage is currently accepting nominations for the 2006 Edward J. Ill Awards. This annual event honors physicians and healthcare professionals in New Jersey who have shown exemplary competence, leadership and commitment to their profession. The award categories are as follows: Edward J. Ill Award Given to an eminent leader in his or her specialty. Medical Educator Award Given to an esteemed educator in academic medicine. Medical Executive Award Given to an outstanding medical executive. Citizen’s Award Given to a leading advocate for healthcare concerns and public welfare. Community Service Leader Award Given to an outstanding organization dedicated to improving the lives of those in need in New Jersey. Nominations are open to all New Jersey physicians and healthcare professionals and may be submitted to: Joseph Reichman, MD c/o MDAdvantage Two Princess Road, Ste. 2 Lawrenceville, NJ 08648 Please forward the nominee’s name, along with a description of qualifications and CV if available. Written nominations will be accepted through December 16, 2005. Recent Drug Safety Issues Recent Drug Safety Issues Drugs Purpose Manufacturer Safety Concerns Accutane Roche Laboratories Treatment of a type of severe acne (nodular acne) that has not been helped by other treatments, including antibiotics Aggressive and/or violent behaviors, birth defects Adderall Shire US Inc. Controlled release amphetamine used to treat patients with attention deficit hyperactivity disorder Arava Aventis Pharmaceuticals Treatment of active rheumatoid arthritis Avandia GlaxoSmithKline Baycol Bayer Fluid retention, potential for heart failure, hepatic failure Oral agent for the treatment of type 2 diabetes (with & without fatal outcome), edema Cholesterol lowering medication belonging to the class of Reports of sometimes fatal rhabdomyolysis (a severe muscle adverse reaction) drugs known as statins Bextra Pfizer Non-steroidal anti-inflammatory (NSAID) Increased risk of heart problems; serious & potentially life threatening skin reactions, including deaths Celebrex Pfizer Cox-2 selective NSAID A very large 3-year trial was halted after interim findings suggested that high doses more than tripled the risk of heart problems. Crestor AstraZeneca Cytotec Searle Duragesic Janssen Pharmaceutica; Labtec (generic) Elidel Novartis Enbrel Immunex Corporation Ephedra Various Fen-Phen American Home Products (fenfluramine); Various (phentermine) Sudden deaths reported in pediatric patients, particularly those with underlying heart defects Rare, serious hepatic injury, and severe infections, including cases with fatal outcome Status Changes made to labeling in 2002. FDA continues to assess reports of suicide or suicide attempts associated with use. Announced in 8/05 that every person using the drug will have to enroll in a national registry in an effort to reduce birth defects. Sale has been suspended in Canada based on U.S. postmarketing reports. Labeling for Adderall XR was changed in U.S. FDA has not taken any other regulatory action to date. In 6/05, the FDA announced it will be investigating all attention deficit hyperactivity disorder drugs in response to reports of serious psychiatric side effects in patients taking Concerta & Ritalin. The prescribing information & monitoring recommendations were updated in 10/03. Product labeling has been updated to reflect the postmarketing experience of the product since its launch in 6/99. Bayer Pharmaceutical Division voluntarily withdrew the drug from the U.S. market in 8/01. FDA asked Pfizer to voluntarily withdraw the drug from the market on 4/7/05. Pfizer agreed to suspend sales and marketing of Bextra in U.S., pending further discussions with FDA. Still on market, but sales have dropped significantly. FDA has concluded that the benefits outweight the potential risks in properly selected & informed patients. FDA asked for revised labeling, including a boxed warning and a Medication Guide. Physicians are encouraged to use the lowest effective dose. FDA required a 5-mg. dose be made available. FDA is evaluating reports of adverse muscle effects with regard to clinical severity & apparent relationship to the drug. Cholesterol lowering medication belonging to the class of Increased risk of myopathy; reports of sometimes fatal drugs known as statins rhabdomyolysis (a severe muscle adverse reaction) A major adverse effect of the obstetrical use is hyperstimulation of the uterus which may progress to Used to reduce the risk of non-steroidal anti-inflammatory uterine tetany with marked impairment of uteroplacental drug-induced stomach ulcers; the drug is also used offblood flow, uterine rupture, or amniotic fluid embolism. Major changes were made to Cytotec labeling in 4/02, label to induce labor and delivery; used as part of the FDA- Pelvic pain, retained placenta, severe genital bleeding, shock, fetal bradycardia, and fetal and maternal death have including the creation of a new labor & delivery section approved regimen for use with mifepristone to induce that provides safety information related to those issues. been reported. abortion in pregnancies of 49 days or less FDA is investigating reports of death & serious side effects. Deaths & overdoses in patients using both the brand name In 6/05, the Duragesic product label was updated to add Pain control (fentanyl transdermal system) Duragesic and the generic product new safety information in several areas. FDA required labeling changes, including the placement of a boxed warning about the potential cancer risk. Because the risks are uncertain, FDA advises drug should be used only as labeled for patients after other prescription Second-line agent for short-term & intermittent treatment treatments have failed to work or cannot be tolerated. of atopic dermatitis The Warnings, Precautions, and Adverse Events sections of Treatment for moderate to severe rheumatoid arthritis the labeling have been revised. FDA has determined that ephedra presents an unreasonable risk of illness or injury. On 4/12/04, a final rule Ephedra products extensively promoted to aid weight loss, Significant adverse health effects, including heart attack & went into effect prohibiting the sale of dietary supplements stroke containing ephedrine alkaloids (ephedra). enhance sports performance, and increase energy In 1997, the manufacturers agreed to withdraw fenfluramine from the market & FDA recommended that patients stop taking the drugs. Phentermine was not taken off the market, as there has been no identified problem with taking this drug alone. A number of lawsuits have been filed against the manufacturers of both drugs. On A combination of drugs (fenfluramine & phentermine) August 28, 2000, the U.S. District Court in Philadelphia commonly used to treat obesity; the combination of the approved the settlement reached with AHP in a nationwide two drugs is considered off label as they were not fen-phen class action suit. approved by the FDA for use together Heart valve disease FDA has issued a public health advisory about a potential cancer risk from use. This concern is based on information from animal studies, case reports in a small no. of patients, and knowledge of how drugs in this class work. Serious infections and sepsis, including fatalities; lymphoma Meridia Abbott Laboratories Treatment of obesity Mifeprex (RU-486) Danco Laboratories Medical abortion Naproxen Bayer (Aleve), Naprosyn (Roche), generic OTC NSAID Natrecor Johnson & Johnson (Scios Inc.) Treatment of patients with acutely decompensated congestive heart failure Neurontin Pfizer (originally ParkeDavis) Epilepsy; also used for many other off-label uses Viramune Boehringer Ingelheim Non-nucleoside reverse transcriptase inhibitor (NNRTI) used in triple antiretroviral regimens to reduce AIDS morbidity & mortality Oxycontin Purdue Pharma Management of moderate to severe pain for an extended period of time Palladone Purdue Pharma Treatment of moderate to severe chronic pain in opiatetolerant patients (extended release capsules) Paxil GlaxoSmithKline Antidepressant (SSRI); also used to treat anxiety, panic, obsessive compulsive disorder, & post-traumatic stress disorder. Use of antidepressants for patients under 18 years has not been approved by FDA (with the exception of Prozac). Use in children & teenagers considered offlabel. Permax Eli Lilly & Co. Management of the signs & symptoms of Parkinson's disease New labeling changes were approved by the FDA in 7/05 to incorporate additional information for patients with renal impairment or renal insufficiency. Lawsuits have been filed Primary pulmonary hypertension (PPH), heart valve disease, against manufacturer alleging it should have known and warned of the serious adverse effects Meridia can cause. mortality FDA is investigating recently reported serious adverse events. A public health advisory was issued in 7/05. Danco Five reported deaths from sepsis or serious bacterial is updating labeling, Medication Guide and Patient infection following treatment Agreement. FDA asked manufacturers of all OTC NSAIDs to revise their labels to include more specific information about potential Increased risk of cardiovascular and cerebrovascular risks. FDA will be analyzing all available information from events (based on emerging information from a long-term studies to determine if further additional regulatory action prevention trial) is needed. Clinical trials are ongoing to assess further the benefits & risks. Manufacturer states it is proactively educating physicians regarding the conditions and circumstances in which the drug should be used. Package insert was updated, but manufacturer has recently been accused of Renal dysfunction, mortality promoting off-label use. In 5/04, Pfizer's Warner-Lambert division pleaded guilty to illegally marketing the drug to treat ailments for which it was not approved. Pfizer, which did not own WarnerLambert when the government said the wrongdoing happened, paid a $430 million fine to settle charges that included defrauding Medicaid. The drug continues to be a top seller. Risk of suicide The labeling has been revised several times to include more information on liver toxicity. Health care providers should weigh the benefits and risks associated with nevirapine use before prescribing nevirapine for the treatment of their HIV-infected patients. Liver toxicity associated with long-term use The DEA has asked Purdue Pharma to change its strategy regarding Oxycontin. In 7/01, at the urging of the FDA, Abuse liability similar to morphine Purdue added a black box warning to drug labels. Purdue Pharma agreed to suspend sales and marketing in 7/05. Prior to that, Palladone had been sold in the U.S. Potential for severe side effects if taken with alcohol due to since 1/05 and has been used by only a small number of time release formulation patients. In 3/04, FDA issued a Public Health Advisory cautioning physicians about the need to closely monitor all patients being treated with antidepressants. The FDA proposed labeling changes, including a 'black box' warning, for 10 antidepressants (Paxil, Prozac, Zoloft, Luvox, Celexa, Serzone, Effexor, Remeron, & Wellbutrin). In 8/04, Glaxo agreed to pay $2.5M to settle a suit by Eliot Spitzer (NY Atty. General) alleging that Glaxo had hidden results from trials. In 9/05, Glaxo changed the Pregnancy subsection of the Precautions labeling sections indicating an increase in Use may increase suicidal thoughts in children & teenagers; the risk of congenital malformations during the first trimester. significant withdrawal symptoms; risk of birth defects During postmarketing surveillance, a small number of individuals have been identified as developing cardiac In 2003, the warnings section of the U.S. Package Insert was valvulopathy involving one or more valves modified. Drugs Pur ose Manufacturer Safet Concerns Nasal decongestant (prescription & OTC); weight control (OTC) Phenylpropanolamine (PPA) Various Increased risk of hemorrhagic stroke in women, and possibly also men. Recent Drug Safety Issues Status FDA requeste t at a rug compa marketing products containing PPA products in 11/00. New labeling adopted in 1/03, inclu states that therapies should not be of cardiovascular disease. Also, estr Hormone replacement therapy used to treat symptoms of of endometrial cancer when used w menopause Premarin Wyeth Pharmaceuticals New a e ing a opte in 1 , inc u Recent Drug Safety Issues Hormone replacement therapy used to treat symptoms of Long-term use significantly increases risk of stroke, blood states that therapies should not be menopause clots, heart attacks & breast cancer. of cardiovascular disease. Prempro Wyeth Pharmaceuticals Janssen cease mar eting Propu si 7/14/00. On 2/4/04, Janssen and the Drugs Safety Concerns Status Committee, through lead counsel, Manufacturer Purpose FDA requested that all drug companies discontinue reached an agreement in principle t marketing products containing PPAlawsuits & remove PPA from related toall the product Prop Johnson & Johnson Nasal decongestant (prescription & OTC); weight control Increased risk of hemorrhagic stroke in women, and (OTC) possibly also men. products in 11/00. Phenylpropanolamine (PPA) Various (Janssen Pharmaceutica) Treatment of severe nighttime heartburn in adults Heart rhythm abnormalities Propulsid (cont’d) Premarin Protopic Prempro Raptiva Propulsid Redux (dexfenfluramine) Remicade Protopic Rezulin Raptiva Redux (dexfenfluramine) Remicade Risperdal Rezulin Serzone Risperdal Serzone Strattera Thimerosal Strattera Tysabri Thimerosal Viagra Tysabri Viagra Vioxx Vioxx Zyprexa Zyprexa NIH stopped a trial after finding the pills not only failed to reduce the risk of heart disease, but raised the possibility of a stroke. Other risks include ovarian cancer, lupus, scleroderma, gallbladder cancer. NIH stopped a trial after finding the pills not only failed to New labeling adopted in 1/03, including a boxed warning, used required for the prevention reduce the risk of heart disease, but raised the possibility states that therapies should not beFDA labeling changes, inc of a stroke. Other risks FDA include ovarian cancer, lupus,health of cardiovascular Also, estrogens increase the risk a boxed warning about the potentia has issued a public advisory aboutdisease. a potential scleroderma, gallbladder cancer. of endometrial cancer when used without a progestin. Wyeth Pharmaceuticals cancer risk from use. This concern is based on information the risks are uncertain, FDA advises New labeling adopted in 1/03, including a boxed warning, for patients after ot fromincreases animal risk studies, case reports in athat small no. ofshould patients, Second-line agentused for to short-term & intermittent treatment therapy treat symptoms of Long-term use significantly of stroke, blood Hormone replacement states therapies not beonly used as for labeled, the prevention treatments have failed to work or ca and knowledge of how drugs inofthis class work.disease. Fujisawa Healthcaremenopauseof atopic dermatitis cancer. clots, heart attacks & breast cardiovascular Wyeth Pharmaceuticals Treatment o a u t patients wit c ronic mo erate to New ytic Janssen ceased marketing Propulsid in theemo U.S. as of anemia warning a 7/14/00. On 2/4/04, Janssen and the Plaintiffs Steering severe plaque psoriasis Hemolytic anemia information in 7/05. Genentech Committee, through lead counsel, announced they had In 1 7, t e manu acturers agree t reached an agreement in principle to resolve all federal American the Home Products market. A Nationwide Class Act lawsuits related to the product Propulsid. Johnson & Johnson (fenfluramine); Various Agreement received Final Judicial A (Janssen Pharmaceutica) Treatment of severe nighttime heartburn in adults Heart rhythm abnormalities Hormone replacement therapy used to treat symptoms of menopause (phentermine) Treatment of obesity Heart valve disease 2002. required labeling changes, including the placement of Acute iver ai ure, jaun ice c oFDA Jo nson Jo nson Treatment o r eumatoi art ritis, ro n's isease, estasis, epatitis, FDA has issued a public health advisory about a potential a boxed warning about the potential cancer risk. Because ankylosing spondylitis (Centocor) lymphoma Warning on hepatotoxicity added to cancer risk from use. This concern is based on information the risks are uncertain, FDA advises drug should be used Par e-Davis Warner-Second-line agent for short-term & intermittent treatment from animal studies, case reports in a small no. of patients, only as labeled, for patients after other prescription treatments have failed to work or cannot be tolerated. of atopic dermatitis drugs inliver this class work. Lambert Treatment of Type II diabetes mellitus and knowledge of howSevere toxicity Product removed from market in 3/ Fujisawa Healthcare Treatment of adult patients with chronic moderate to New hemolytic anemia warning added n to the , prescribing sent warn ng etters to severe plaque psoriasis Hemolytic anemia information in 7/05. Genentech drug's elevated risk of stroke in elde In 1997, the manufacturers agreed to withdraw Redux from FDA announced that older patients the market. A Nationwide Class Action Settlement American Home Products antipsychotic Agreement received Final Judicial given Approval on January 3, medicines are m (fenfluramine); Various prematurely, & now requires black b (phentermine) Treatment of obesity Heart valve disease 2002. Acute liver failure, jaundice/cholestasis, & Johnson hepatitis, Johnson medicines (Zyprexa, Symbyax, Seroq Johnson Increased risk of & Johnson Treatment of rheumatoid arthritis, Crohn's disease, & diabetes, neuroleptic malignant ankylosingTreatment spondylitis of schizophrenia (Centocor) lymphoma Warning on hepatotoxicity added to labeling in 12/04. Geodon). (Janssen Pharmaceutica) syndrome, stroke, tardive dyskinesia Parke-Davis/Warnern 5 1 4 Bristo Myers qui an Lambert Treatment of Type II diabetes mellitus Severe liver toxicity Product removed from market in 3/00. Serzone in the U.S. This follows a In 4/03, J&J sent warning letters toselling U.S. physicians citng Antidepressant Liver damage 2001. Bristol Myers Squibb patients. In 4/05, drug's elevated risk of stroke in elderly FDA announced that older patientsnwith dementia , a ewho ng are was up ate to n given antipsychotic medicines are more likely die the FDA announced effects. Into6/05, prematurely, & now requires black all boxattention warnings on related deficit hyperactivity dis medicines (Zyprexa, Symbyax, Seroquel, Abilify, Clozaril, Johnson & Johnson Increased risk of diabetes, neuroleptic malignant to reports of serious psychiatric side (Janssen Pharmaceutica) Treatment of schizophrenia syndrome, stroke, tardive dyskinesia Geodon). taking Concerta & Ritalin. On 9/29/0 On 5/19/04 Bristol Myers Squibb announced it would stop Advisory Severe drug related liver injury; selling reports of suicidal thinking Serzone in U.S. This follows Health a black box warningto in alert physicians o Antidepressant 2001. Bristol thinking in children & adolescents. Treatment of attention deficit disorder Liver damage in children & adolescents EliMyers Lilly Squibb & Co. In 12/04, labeling was updated to include serious liver side A mercury-containing organic compoun an FDA as wor e wit , an continue effects. In 6/05, the FDA announced it will be investigating organomercurial); the most common preservative used in Theoretical potential for neurotoxicity manufacturers of even levels ofdisorder to reduce or eliminat deficitlow hyperactivity drugs in response all attention vaccines & biologics that are marketed in the U.S. organomercurials vaccines. Various to reports of serious psychiatric side effects in patients Ritalin. On 9/29/05, FDA issued a Public A patient in a ong-term c inica taking tria Concerta ie rom& progressive Advisory alert physicians Biogen-IDEC of reports of suicidal Severe drug related liver injury; reports of suicidal thinking Health has suspended marke multifocal leukoencephalopathy (PML), a raretoneurologic in children & adolescents. in children & adolescents Eli Lilly & Co. Idec & Elan Treatment of attention deficit disorder Biogen disease; a second patient in thethinking same trial had a confirmed dosing of patients in on-going clinic A mercury-containing organic compound (an FDA has worked with, and continues to work with, vaccine diagnosis of PML. concurs withfrom this decision Pharmaceuticals Treatment for common relapsing forms of used multiple sclerosis potential for organomercurial); the most preservative in Theoretical neurotoxicity of even low levels of manufacturers to reduce or eliminate thimerosal vaccines & biologics that are marketed in the U.S. Various Pfizer Biogen Idec & Elan Pharmaceuticals Pfizer Erectile dysfunction from the market. There A small number of post-marketing reports of sudden vision In 7/05, FDA approved updated labeling for Viagra, Cialis loss, attributed to non-arteritic ischemic optic neuropathy & Levitra to reflect the rare ocular occurrences. pending against Merck Cox-2 selective NSAID Merck Merck Eli&Lilly Eli Lilly Co. & Treatment for relapsing forms of multiple sclerosis organomercurials vaccines. A patient in a long-term died from progressive Aclinical small trial number of post-marketing reports of sudden vision In 7/05, FDA approved updated lab has neuropathy suspended marketing and allto further Biogen-IDEC multifocal leukoencephalopathy (PML), a rare neurologic & Levitra reflect the rare ocular o loss, attributed to non-arteritic ischemic optic disease; a second patient in the same trial had a confirmed dosing of patients in on-going clinical trials. The FDA concurs with this decision diagnosis of PML. Erectile dysfunction Co. Merck announced in 9/04 that it was are an estim in associatio In the first Vioxx trial, a Texas jury or Merck announced in 9/04 that it was withdrawing drug stunning $253 million to a widow wh from the market. There are an estimated 5,000 suits heart after taking the me pending against Merck in association witharrhythmia the drug Vioxx. vowed to appeal In the first Vioxx trial, a Texas jury ordered Merck to paythe a case, which wi $26 million stunning $253 million to a widow whose husbanddue diedto of caps on punitive heart arrhythmia after taking the medication. Merck has second Vioxx trial is currently under Increased risk for heart attacks & strokes vowed to appeal the case, which will likely be cut to about $26 million due to caps on punitive damages in Texas. The Labeling changes made second Vioxx trial is currently underway in Atlantic City, NJ. in 3/04 re: m atypical antipsychotics with an estab Cox-2 selective NSAID Increased risk for heart attacks & strokes Atypical antipsychotic Atypical antipsychotic forpatients diabetes Labeling changes made in 3/04 re: factors monitoring on mellitus and mo atypical antipsychotics with an established diagnosis or risk symptoms of hyperglycemia. In 4/05 factors for diabetes mellitus and monitoring all patients older patients withfordementia who a symptoms of hyperglycemia. In 4/05, FDA announced that medicines are more likely to die pre older patients with dementia who are given antipsychotic requires black medicines are more likely to die prematurely, & now box warnings on rela (Risperdal, Symbyax, Seroquel, Abil requires black box warnings on related medicines (Risperdal, Symbyax, Seroquel, Abilify, Clozaril, Geodon). in 6/05 that it ha Eli Lilly announced Lillydiabetes announced 6/05 that it has entered intoinanprinciple to settle abo agreement Increased risk of hyperglycemiaEli and ininpatients agreement in principle to settle about 8,000 (75%) of claims Increased risk of hyperglycemia and diabetes in patients against the company related to Zyp takingmedications atypical antipsychotic medications against the company related to Zyprexa. taking atypical antipsychotic Note: For purposes only. This table lists somelists of the mostof notable recentnotable drug safety concerns, is notconcerns, meant or intended to be an exhaustive or wholly Note: Forrepresentative representative purposes only. This table some the most recent drugand safety and is not meant or intended to be an exhaustive or wholly accurate list. Information in this table does not constitute medical advice and it serves no other purpose than to provide additional background material. Further accurate list. Information in this table does not constitute medical advice and it serves no other purpose than to provide additional background material. Further information on a particular drug can be found either from the FDA (www.fda.gov) or the drug manufacturer. information on a particular drug can be found either from the FDA (www.fda.gov) or the drug manufacturer. Navigating Drug Safety Issues: The Physician’s Perspective (cont’d) could become overburdened and take longer to reach trial. Additionally, the federal court takes a conservative approach and may tend to deny class certification. Pursuit of Damages: the Collectible Claim The first hurdle for a claimant to overcome in establishing a claim is the statute of limitations, which is the time limit or deadline that the injured party has to file his or her claim. (Each state has its own variation of the statute of limitations.) The individual actions which have been filed may then be qualified as part of a mass tort. In New Jersey, the statute of limitations is two years from the date the cause of action accrued. Often the date the cause of action ”accrued” is different than the date of treatment. The so-called discovery doctrine provides that statute does not start to run until the patient becomes aware of the injury and is aware that the injury is due to the fault of an identifiable party. This can allow a claimant significant extensions of time to initiate a lawsuit when there is a delayed manifestation of injury or the issue of fault is not self-evident. The situation is different for the individual patient who may be part of a “class.” In class action suits, one or more members of a class may sue on behalf of all members of the class. Therefore, the individual patients are covered as members of the class without actually filing suit themselves. The filing of the complaint seeking class action certification tolls the statute of limitations for the benefit of all members of the potential class. After the statute question has been answered and a claimant has determined if the basis of a suit is truly product liability or an act of medical negligence on the part of a health care provider (medical malpractice), there are other major obstacles to overcome – both in mass tort litigation and class action suits. In pursuit of a product liability claim, it is the job of the plaintiff attorney to establish causation, which may be difficult for “latent injuries” which may not yet be evident. In their pursuit of money as compensation for damages they have suffered or will incur in the future, plaintiffs are usually seeking to collect both compensatory and punitive damages from the defendants. The term “compensatory damages” covers a number of categories of loss, both economic and non-economic. Economic damages include lost wages, decreased earning capacity and other items of pecuniary loss. Non-economic damages (often the subject of discussion and debate on the topic of damage caps and tort reform) include elements of pain and suffering, physical impairment, disfigurement, loss of enjoyment of life and other non-pecuniary damages. The big ticket item in terms of jury awards is punitive damages (damages awarded separately and in addition to compensatory damages as punishment for the wrongdoer). In the first Vioxx trial in Texas, the major portion of the $253 million award was $229 million in punitive damages. Many states, including Texas and New Jersey, have some type of cap on punitive damage awards. In the Vioxx trial, total awards are likely to be cut to about $26 million as a result of a cap on punitive damages in Texas7. The Less Vulnerable Physician? Physicians, from a practical standpoint, are not named in large class action suits. As demonstrated however in many of the past product liability suits, individual physicians have been named as direct defendants or third party defendants in individual or mass tort suits. In many of these actions (such as breast implant and diet drugs), manufacturers waged their own defense by arguing that physicians had adequate information about the risks of utilizing or prescribing their products. Physicians also 888-355-5551 • www.MDAdvantageonline.com became vulnerable to lawsuits which began as mass tort product liability suits but diverged into concurrent or subsequent medical malpractice claims. The relationship between physicians and product manufacturers remains strained and uncertain. However, the tactics that plaintiff attorneys appear to be taking in the latest high profile or newsworthy product liability cases are “cautiously encouraging” for physicians. Trends are showing that physicians are not being named in more recent mass tort litigation, such as in the case of Vioxx. Strategically, the cases are being geared exclusively toward the large manufacturers. Plaintiffs are taking the stance that patients and their physicians were not adequately warned of the risk of the products. Large manufacturers have been avoiding filing third party claims against physicians (their customers) for inappropriate use of the product or device. The first of the mass tort trials for a particular drug, class of drugs, or device is strategically critical for both plaintiffs and the defense. Although physicians generally are not being named as defendants in these newest cases, the trend can of course change in the future based on the outcomes of the initial trials. For example, the first Vioxx case has been closely analyzed. Merck has vowed to fight each Vioxx case one by one and says it has a strong case on appeal in the recently completed Texas trial. In the second Vioxx trial, which is underway in Atlantic City, and the first federal Vioxx case, expected in November, the opposing sides will plan strategically from lessons learned in the first trial. Monitoring the progress of these trials will enable physicians to gather information on what, if any, potential liability issues may be brought up in the future. The conclusion of this article will be published in the Winter Edition of MDAdvisor. Topics covered will include an overview of how physicians are responding to drug safety issues and guidelines for minimizing liability and ensuring safe and effective care to patients. The article will also include a summary of recent interviews with relevant parties such as physicians and a claimant attorney. If you are a physician interested in providing comments on this article or would like to share how your practice is handling these drug safety issues, please contact Janet Puro at [email protected] or (888) 355-5551 x1197. Comments may also be mailed to MDAdvantage, Two Princess Road, Suite 2, Lawrenceville, NJ 08648. References 1 Press Statement, Food & Drug Administration, Statement on First Meeting of FDA’s Drug Safety Oversight Board. (2005, June 17). 2,4 Berenson, Alex. (2005, May 31). Despite Vow, Drug Makers Still Withhold Data. The New York Times. 3 Harris, Gardiner. (2005, February 17). Medical Panel Poses Pointed Questions to Drug Makers Over Risks of Painkillers. The New York Times. 5,7 Business: The Week Ahead. (2005, September 15). Merck’s Vioxx Drama Moves to New Jersey Venue. The Star-Ledger, p. 24. 6 Amoresano, Guy V. and Michael R. McDonald. (2005, April 25). Class Litigants Face Tougher Forum. New Jersey Law Journal. Robert B. Goley is the Vice President of Claims Administration at MDAdvantage. He and Ms. Puro, Project Specialist, have been frequent authors on tort reform and other issues affecting New Jersey physicians. PRESORTED FIRST CLASS MAIL US POSTAGE PAID PRINCETON, NJ PERMIT NO. 47 Two Princess Road, Ste 2 Lawrenceville, NJ 08648 Return Service Requested If you would like to provide us with your comments or provide a suggestion for a future issue of MDAdvisor, please email us at [email protected]. Risk Management Seminars Mark Your Calendar! MDAdvantage will be presenting the following risk management seminars. November 9, 2005 Come visit the MDAdvantage Exhibit Booth at the New Jersey Physician’s Expo! We will also be presenting a one-hour seminar, The Most Vulnerable Physician: A Review of the Top Reasons Doctors are Sued Meadowlands Expo Center, Secaucus November 12, 2005 Effects of Malpractice on Physicians Barry Brown Health Education Center, Voorhees Please keep an eye on your mail for other future risk management seminars! You can also find details, as they become available, in our Events section of www.MDAvantageonline.com. 24-7 Claim Assistance MDAdvantage is committed to quality service. We are pleased to provide you with 24-7 access to our claim professionals. To reach a claim representative outside of business hours, call 888-355-5551 and follow the prompt for emergency assistance. You will be requested to leave a message and phone number where you can be reached. A claim representative will be paged and will return your call as quickly as possible.