Leading Pharmacy News

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Pfizer Says Two Cancer Drugs Failed In Clinical Trials.

Bloomberg News (3/12, Olmos) reports, "Pfizer Inc. said the cancer drug Sutent [sunitinib] failed to halt the progression of advanced breast tumors in two studies." Researchers found that "Sutent used as an initial treatment in combination with chemotherapy didn't show a 'statistically significant' improvement in slowing the growth of advanced breast cancer compared with chemotherapy alone." Meanwhile, a second study showed that "Sutent used with a different chemotherapy drug didn't slow the spread of breast cancer in previously treated patients when compared with chemotherapy alone."

The AP (3/12) reports, "The drug is already sold as a treatment for advanced kidney cancer and gastrointestinal stromal cancer." Dr. Mace Rothenberg, senior vice president of clinical development and medical affairs at Pfizer's oncology business unit, said that although the company is "disappointed in the results, these trials have helped us define the limits and opportunities for the compound."

Pfizer also "said...it discontinued a late-stage study of the drug candidate figitumumab in patients with late-stage lung cancer, citing a lack of effectiveness," the AP (3/12) reports in a separate article. The move follows a recommendation from "an independent monitoring committee" to halt the study. The panel "concluded that figitumumab in conjunction with Tarceva [erlotinib] will likely not significantly improve the overall survival rate of patients."

But, Dow Jones Newswire (3/12, Kell, subscription required) reports that the company said it intends to continue clinical trials of figitumumab for prostate, breast, and lung cancers. Reuters (3/12, Beasley) also covers the story.

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Oral Contraceptives May Reduce Risk Of Death From Any Cause In Women.


Bloomberg News (3/12, Cortez) reports that, according to findings published in the British Medical Journal, women who use oral contraceptives "were less likely to die of heart disease, cancer, or a range of other medical ailments." In fact, "women who took the pill were 12 percent less likely to die from any cause during the study." The study also showed that "the risk of death was slightly higher in women under age 45 who were current or recent users, though it abated after 10 years." Data indicated that "overall, there were 52 fewer deaths than expected for every 100,000 women taking the pill each year."

MedPage Today (3/11, Fiore) reports that researchers "found lower rates of death from circulatory disease, ischemic heart disease, and other disease among women who'd used birth control pills," as well as "all cancers." Notably, "women on the pill did have higher rates of violent deaths," but "the researcher said they had no explanation for this association."

PCV13 Could Further Reduce Pneumococcal Disease Among Children Under Five.

MedPage Today (3/11, Fiore) reported, "PCV13 in the routine immunization schedule has the potential to further reduce [pneumococcal disease]...among children under five," according to research published in the CDC's Morbidity and Mortality Weekly Report. "Among all cases of invasive pneumococcal disease in 2007, 64% were covered by serotypes contained in the PCV13 vaccine (Prevnar 13), which covers six more disease strains than the PCV7 shot." Investigators did point out that the PCV7 did prompt the "so-called 'herd' effect," but "whether this will apply to the other six serotypes in the PCV13 vaccine remains to be determined."

Older Hyperkalemia Agents May Be Ineffective, Potentially Dangerous.
MedPage Today (3/11, Emery) reported that, according to a study published online in the Journal of the American Society of Nephrology, drugs containing ion exchange resins, which have been used since 1958 to treat patients with hyperkalemia, may be "ineffective and potentially dangerous." In fact, "certain suspensions of sorbitol and sodium polystyrene sulfonate, referred to as SPS and marketed as Kayexalate," have been implicated in reports of bowel injuries which could prove fatal. The study authors concluded, "If Kayexalate or SPS in sorbitol were presented to the FDA as new drugs with the data available today, it is doubtful that either would pass muster."

Roche Says Avastin Fails To Meet Goal In Prostate Cancer Study.
The Wall Street Journal (3/12, Gelnar, subscription required) reports that Roche Holding AG said that its drug Avastin (bevacizumab) did not meet a key goal in a prostate cancer study.

Bloomberg News (3/12, Sargent) reports that, according to Roche, "a combination of the biologic, chemotherapy, and the prednisone medication didn't extend overall survival compared with treatment with the latter two drugs alone." Bloomberg notes that "the final-stage study was sponsored by the US Cancer and Leukemia Group B and the National Cancer Institute." Reuters (3/12) also covers the story.

Merck Says It Will Continue Study Of Vytorin Effectiveness.

The AP (3/12, Johnson) reports that "researchers will continue a study of a controversial Merck & Co. cholesterol drug," Vytorin (ezetimibe and simvastatin), "after safety monitors decided data so far indicate the drug is safe and effective, the company said Thursday." Merck "said the data safety monitoring board overseeing the study, called IMPROVE-IT, did a preplanned analysis of results halfway through the study." The research "is intended to determine whether Merck's combination cholesterol pill Vytorin prevents heart attacks, strokes, and deaths more than just one of its components, Zocor [simvastatin], which is available as a cheap generic pill." Reuters (3/12, Pierson) also covers the story.

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Understaffed and overwhelmed

If you are accused of a crime in this country, you have a right to a speedy and public trial. You will probably not get one.

From the moment individuals enter the criminal justice system, they are pressured to give up this right, as the system simply could not cope if everyone exercised it. Understaffed and overwhelmed, the criminal justice system is forced to get by as best it can, crossing its fingers and hoping that most of the people it encounters can be talked out of demanding that it meet its obligations to them.
Sound familiar? If not, substitute the words "have a prescription filled" for "accused of a crime," "be counseled by a pharmacist" for "a speedy and public trial," and "healthcare" for "criminal justice" and reread that first paragraph. We have more in common with lawyers than we might like to think.

Some math will show you why. Let's say a pharmacy fills a thousand prescriptions a day, not uncommon in this age of the industrial drugstore. Now let's say it takes an average of three minutes to go over the eight point OBRA checklist with each customer and address any other concerns they may have.

Run the numbers and you'll see that if you freed the pharmacist from all the lick, stick, and pour tasks of the profession, and if somehow you were able to exempt the pharmacist from taking telephoned prescriptions and getting transfers from other pharmacies, and if the whole day went by without a patient asking a question over the phone, and if you chained the pharmacist to the pickup window to do nothing but counsel, you would need 50 pharmacist hours in that store every day. And that assumes the customers came in at a nice steady rate over the course of 24 hours.

Fifty pharmacist hours will easily cost a company over $3,000, including benefits. Which means that a pharmacy filling a thousand prescriptions a day has to make three dollars a prescription just to pay for a pharmacist's counseling duty. Most insurance companies pay a dispensing fee of around $1.50 per prescription, meaning that we will never come close to being able to give our patients a scant three minutes of our time. The numbers simply don't allow it.

So we don't do it. We do "counseling triage," pulling customers aside to talk to them when we must, making sure they were expecting a painkiller when a doctor's handwriting makes "Celebrex" look a little too much like "Celexa," checking that the endocrinologist knew his patient was taking warfarin when he wrote that Synthroid prescription.

For the rest, we cross our fingers and hope that most customers can be talked out of the time with us to which they are legally entitled. Because if the Bill of Rights of this country's Constitution can't ensure that a nonprofit legal system will provide the rights to which our citizens are entitled, what are the chances that a budget reconciliation act will compel compliance from a corporation that has to show earnings growth from quarter to quarter?

Remember that, the next time your boss tries to get you excited about some new technology or reorganization that will "free the pharmacist to counsel." Show your boss the numbers I just laid out here and announce that you're looking forward to the new pharmacist labor budget of three minutes per prescription. Then watch your boss turn pale and pass out.

I've been hearing about changes that will "free me to counsel" since the day I entered pharmacy, but somehow I had far more time for my patients the day OBRA passed in 1990 than I ever do today. Perhaps it will take a constitutional amendment to get that time back. Or an increase in insurance reimbursement rates. You decide which is more likely.

I'll let you get back to work now. Don't forget to keep saying those magic words, "Did you need me to go over your medicine with you?"

Remember though, you have a doctor holding on line one.

David Stanley is a practicing community pharmacist in California. He can be reached at drugmonkeyrph@gmail.com

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Step-Up Therapy Improves Asthma Control in Children

Step-Up Therapy Improves Asthma Control in Children

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Clinical Context


There are many treatment options for childhood asthma, yet few high-quality trials have helped to direct therapy. The Pediatric Asthma Controller Trial, which was published by the authors of the current study in the January 2007 issue of the Journal of Allergy and Clinical Immunology, compared inhaled fluticasone alone, inhaled fluticasone plus salmeterol, and montelukast alone among 258 children with mild to moderate asthma and a forced expiratory volume in 1 second (FEV1) of 80% of the predicted value or more.

Overall, fluticasone monotherapy was similar to fluticasone plus salmeterol in the percentage of days with asthma in control, but fluticasone monotherapy was associated with better FEV1/forced vital capacity and better maximal bronchodilator response. Fluticasone monotherapy was superior to montelukast in both asthma control days and pulmonary function testing. Growth was similar in all randomized groups. Nonetheless, more than half of the children in the Pediatric Asthma Controller Trial had episodes of uncontrolled asthma.

The current trial presented at the AAAAI annual meeting focuses on the best treatment in children who do not achieve good asthma control with an ICS alone.

Study HighlightsClinical Implications

A previous trial comparing treatment in children with mild to moderate persistent asthma demonstrated that fluticasone monotherapy was superior to montelukast in both asthma control days and pulmonary function testing. Growth was similar with all study treatments.
In the current study of children with uncontrolled asthma while receiving an ICS, step-up therapy with salmeterol was associated with a better response to treatment than step-up therapy with either high-dose inhaled fluticasone or montelukast.

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Prostate Cancer

Prostate Cancer

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FDA Adds Boxed Warning To Plavix.
The AP (3/13, Perrone) reported that the FDA "is adding its strongest warning to the label for Plavix [clopidogrel bisulfate], cautioning that some patients do not respond to the blockbuster blood thinner." According to the Los Angeles Times (3/12, Maugh) "Booster Shots," the "warning indicates that the drug is dangerous only in the sense that it doesn't work in" certain "patients and thus may leave them unprotected against heart attacks and strokes."
Specifically, some patients have a difference in a liver enzyme known as CYP2C19, which helps to convert Plavix to a form that the body can use, Dow Jones Newswire (3/12, Dooren, subscription required) reported. Notably, FDA officials said CYP2C19 tests typically cost less than $500.
Robert Temple, deputy director for clinical science at the FDA's Center for Drug Evaluation and Research, said, "What there hasn't been is a clear test of whether you can take people who are poor metabolizers, double their dose and do just as well," according to Bloomberg News (3/12, Peterson, Larkin).
Reuters (3/12), AFP (3/15), MedPage Today (3/12, Gever), HealthDay (3/12, Reinberg), WebMD (3/11, DeNoon), Medscape (3/12, Lowes) and CQ HealthBeat (3/12, subscription required) also covered the story.

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1. Hemolysis Warning Added to WinRho SDF Labeling

FDA on March 10 announced the addition of a boxed warning to the labeling of WinRho SDF because the product has been associated with sometimes-deadly cases of intravascular hemolysis in patients with immune thrombocytopenic purpura.

http://www.ashp.org/import/news/HealthSystemPharmacyNews/newsarticle.aspx?id=3293

2. New Boxed Warning for Clopidogrel Addresses Pharmacogenomics

Health care professionals planning to prescribe clopidogrel should consider using "alternative treatment or treatment strategies" in patients identified as poor metabolizers of the prodrug, according to the new boxed warning in the medication's FDA-approved labeling.

http://www.ashp.org/import/news/HealthSystemPharmacyNews/newsarticle.aspx?id=3299

3. Oral Bisphosphonate Users May Be At Risk of Femur Fracture

FDA on March 10 announced it has not found a "clear connection" between the use of oral bisphosphonates and a risk of atypical fractures in the bone below the hip joint. The announcement came after two presenters at a national medical meeting said their research suggested that bisphosphonates, if used for four or more years, may impair bone quality.

http://www.ashp.org/import/news/HealthSystemPharmacyNews/newsarticle.aspx?id=3294

4. FDA Unveils Risk-Management Program for ESAs

The risk-management program for erythropoiesis-stimulating agents that FDA unveiled in February is receiving a less-than-enthusiastic response from hospital pharmacists.

http://www.ashp.org/import/news/HealthSystemPharmacyNews/newsarticle.aspx?id=3297

5. Reduce Use of Long-Acting Beta2-Agonists in Asthma Therapy, FDA Says

Long-acting beta2-adrenergic agonists have a favorable risk:benefit ratio in asthma therapy only for those patients whose disease is inadequately controlled by asthma-controller medications, FDA officials announced February 18.

http://www.ashp.org/import/news/HealthSystemPharmacyNews/newsarticle.aspx?id=3295

6. Everyone Needs Seasonal Flu Vaccination, CDC Advisers Say

Seasonal influenza vaccines should protect against the pandemic 2009 H1N1 virus, and every American over the age of six months should receive a vaccine starting this fall, advisers to FDA and the Centers for Disease Control and Prevention declared in February.

http://www.ashp.org/import/news/HealthSystemPharmacyNews/newsarticle.aspx?id=3298

7. Share Your Views on Proposed ASHP Professional Policies

All ASHP members are encouraged to log in to ASHP's online discussion forum, ASHP Connect, to review, comment on, and discuss proposed ASHP professional policies that will be considered by the ASHP House of Delegates in June 2010. ASHP professional policy is developed and approved by ASHP members, so make your voice heard by participating in the discussion. Simply click on the URL below, enter your e-mail address and password, and select the category "House of Delegates."

http://www.ashp.org/ashpconnect

8. ISMP Issues Guidelines for Standard Order Sets

A 100-item checklist has been developed by the Institute for Safe Medication Practices to help health care organizations ensure that they follow the elements of safe order communication when designing paper-based or electronic order sets.

http://www.ismp.org/Tools/guidelines/StandardOrderSets.pdf

9. CDC Advisers Recommend PCV13 Over PCV7 When Available

The new 13-valent pneumococcal conjugate vaccine, when available to a vaccination provider, should be administered to children instead of the older 7-valent pneumococcal conjugate vaccine, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recently decided.

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5909a2.htm

10. Six New Drugs Gain 'Pass-Through' Status in OPPS

Starting April 1, Medicare's hospital outpatient prospective payment system recognizes the following drug products as having "pass-through" status: ecallantide injection, fludarabine phosphate oral tablets, ofatumumab injection, pralatrexate injection, telavancin injection, and ustekinumab injection. (Please note that the billing unit for each of these products differs from the vial size or tablet strength.)

http://www.cms.hhs.gov/MLNMattersArticles/downloads/MM6857.pdf

11. One Month Left To Submit Comments on USP Chapter on QA in Compounding

April 15 is the deadline for submitting comments on proposed revisions to United States Pharmacopeia chapter 1163, "Quality Assurance in Pharmaceutical Compounding." (Scroll down on the USP Web page to find the link to the document.)

http://www.usp.org/USPNF/pf/1163comments.html

12. ClindaReach Pledgets Stolen at Truck Stop

Sirius Laboratories, a subsidiary of Dusa Pharmaceuticals Inc., said four complete lots of ClindaReach kits were stolen in early February while in transit. According to an article at SecuringPharma.com, the trailer of ClindaReach kits had been left at a truck stop on a Saturday and was not there when the driver returned the next day.
http://www.dusapharma.com/for-pharmacists.html (Dusa announcement)
http://www.securingpharma.com/40/articles/381.php (SecuringPharma article)

13. New Leadership Videos Now on ASHP Foundation Website

http://www.ashpfoundation.org/leadershipvideos

14. Present Your Work in Tampa! Call for 2010 Summer Meeting Posters

http://www.ashp.org/Get_Involved

15. Call for Nominations: John W. Webb Lecture Award

The John W. Webb Lecture Award recognizes a hospital or health-system pharmacy practitioner or educator who has distinguished herself or himself through extraordinary dedication to fostering excellence in pharmacy management. The ASHP Section of Pharmacy Practice Managers is seeking nominations of candidates for the 2010 award. Deadline for submission is April 6.

http://www.ashp.org/Import/ABOUTUS/Awards/WebbAward.aspx

16. Is Your Residency Program Innovative? Present Pearl or Poster at Natl. Residency Conference

Now's your chance to share your work with peers on a national level. ASHP seeks pearl and poster proposals for presentation at this year's National Residency Preceptors Conference, August 19-21 in the heart of downtown Washington, D.C. The deadline is May 3.

http://www.ashp.org/PreceptorsConference

17. Apply for 2010 Pharmacy Residency Excellence Awards by July 1

http://www.ashpfoundation.org/MainMenuCategories/Awards/

PharmacyResidencyExcellenceAwards.aspx

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As House Readies For Vote, Democrats' Healthcare Strategy Creates Controversy.FDA Approves Cardizem LA Generic.
The AP (3/16) reports, "Watson Pharmaceuticals Inc. said Monday a Florida subsidiary received government approval for a generic equivalent of the blood pressure drug Cardizem LA [diltiazem hydrochloride]." The company "intends to launch the generic immediately."
Regulatory
FDA Seeks Risk Management Plan, Labeling Clarification For Once-Weekly Version Of Byetta.
Bloomberg News (3/16, Waters, Pettypiece) reports that the FDA "said they didn't need more studies for a once-weekly version of the diabetes drug Byetta [exenatide]" from Amylin Pharmaceuticals Inc. and Alkermes Inc. But the FDA did ask "for clarification of manufacturing processes, labeling and a risk-management plan, the companies said today in a statement."
The AP (3/15) noted that the new drug will be called Bydureon, and "Amylin said it is 'working diligently' to submit a response to the FDA in the next few weeks." The San Diego Union-Tribune (3/16, Kupper) and Reuters (3/16, Clarke) also covered the story.
FDA To Review Trilipix Label.
Dow Jones Newswire (3/16, Kell, subscription required) reports that the FDA said it will review the label of the cholesterol drug Trilipix following the release of a negative study of a similar predecessor drug called TriCor [fenofibrate. The FDA said it has made "no new conclusions or recommendations" about the data from the study, which showed TriCor failed to significantly reduce the risk of heart attacks and strokes among diabetics.
FDA Seeks More Information On Inhaled Insulin Drug.
Bloomberg News (3/16, Waters, Wechsler) reports MannKind Corp. "failed to win approval from US regulators to market its inhaled insulin drug, Afrezza, for people with diabetes." The FDA "asked for more information about the medication and the inhaler patients will use, MannKind said today in a statement," and although the agency "didn't cite any safety concerns, they requested updated safety data." A MannKind employee also said the FDA questioned whether the inhaler used in clinical trials was similar to another one the company created and wants to market with Afrezza. The AP (3/16) and the Los Angeles Business Journal (3/15) also covered the story.
BioSante Receives Orphan Drug Status For Potential Pancreatic Cancer Treatment.
The AP (3/15) reported, "BioSante Pharmaceuticals has received orphan drug status for its potential pancreatic cancer treatment, the company said Monday." BioSante's GVAX Pancreas Vaccine is currently "undergoing clinical trials with other anticancer agents for safety, survival and response rates." The vaccine "treats existing cancers," but "it does not prevent them." Under the designation, BioSante will have "seven years of market exclusivity following FDA approval, assistance in clinical trial design, a reduction in user

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Oral contraceptive use is not associated with increased long-term mortality rates, according to the results of a large, prospective UK cohort study reported in the March 11 issue of the BMJ.

"The Royal College of General Practitioners' (RCGP) Oral Contraception Study is one of the world's largest continuing investigations into the health effects of contraceptive pills," write Philip C. Hannaford, MD, from the University of Aberdeen, Foresterhill Health Centre, United Kingdom, and colleagues from the RCGP's Oral Contraception Study.

No Association Between Mortality and Oral Contraceptive Use

"Early reports from the study indicated an increased risk of death among ever users of these contraceptives, mainly because of an excess of vascular events among older users or those who smoked," the study authors write. "A later report, based on up to 25 years of follow-up, suggested that most of the mortality effects of oral contraceptives occurred in current or recent users, with few effects persisting beyond 10 years after stopping use."

The objective of the study was to see if the mortality risk among women who have used oral contraceptives differs from that of never-users. The cohort study began in 1968, with mortality data provided by participating general practitioners (GPs) at 1400 general practices throughout the United Kingdom, National Health Service central registries, or both.

Participants were 46,112 women observed for up to 39 years, resulting in 378,006 woman-years of observation among never-users of oral contraception and 819,175 among ever-users. The main study endpoints were directly standardized adjusted relative risks for all-cause and cause-specific mortality between never-users and ever-users.

There were 1747 deaths in never-users of oral contraception and 2864 in ever-users. Ever-users of oral contraception had a significantly lower rate of all-cause mortality vs never-users (adjusted relative risk, 0.88; 95% confidence interval; 0.82 - 0.93). Rates of death from all cancers; large bowel/rectum, uterine body, and ovarian cancer; main gynecologic cancers combined; all circulatory disease; ischemic heart disease; and all other diseases were also significantly lower in ever-users vs never-users. However, rates of violent deaths were higher in ever-users vs never-users.

Although there was no apparent association between overall mortality rate and duration of oral contraceptive use, some disease-specific associations were observed. Compared with never-users, women younger than 45 years who had stopped using oral contraceptives 5 to 9 years previously had an increased relative risk for death from any cause, but those with more distant use did not. Among ever-users of oral contraception, the estimated absolute reduction in all-cause mortality rate was 52 per 100,000 woman-years.

Strengths and Limitations of Study

When asked for independent comment by Medscape Ob/Gyn and Women's Health, Ward Cates, MD, MPH, president of research at Family Health International in Durham, North Carolina, noted various strengths and weaknesses of the study.

"[This was a] well done prospective cohort study of long-term complications from contraceptive choices; the exposure variable (contraceptive use) was regularly assessed; and the outcome variable (mortality) is an objective endpoint (indeed, the ultimate endpoint)," Dr. Cates said.

Study limitations noted by Dr. Cates were that exposures were not randomized, creating the potential for unmeasured selection and/or confounding; and previous articles from this database have acknowledged a relatively high rate of loss-to-follow-up (33%).

Do Results Apply to US Women?

Dr. Cates believes that the clinical implications of this study for US women are similar to those for UK women.

"Oral contraception was associated with a decreased long term risk of death in this large UK cohort," Dr. Cates told Medscape Ob/Gyn and Women's Health. "Thus providers can reassure women who have ever used oral contraceptives not only that they are not at increased [risk of] mortality from ever having used combined oral contraceptives but also that they may even have a net mortality benefit from their choice of contraception."

Regarding additional research, Dr. Cates recommended examining other long-term cohort studies of women using contraception to see if the findings are consistent with the findings from this UK study.

"Perceptions about the safety of oral contraception depend on whether current, recent, or more distant use of oral contraception is being assessed," the study authors conclude. "The balance of risks and benefits, however, may vary around the world, depending on patterns of oral contraception usage and the prevalence of different diseases."

The study received funding from the RCGP, Medical Research Council, Imperial Cancer Research Fund, British Heart Foundation, Cruden Foundation, Schering AG, Schering Health Care, Wyeth Ayerst International, Ortho Cilag, and Searle. The Centre of Academic Primary Care has received payments from Schering-Plough and Wyeth Pharmaceutical for lectures and advisory board work provided by Dr. Hannaford. Dr. Cates is an author of the textbook Contraceptive Technology, now in its 19th edition, and has disclosed no other financial relationships.

BMJ. 2010;340:c927. Abstract

Clinical Context

Early reports from the RCGP Oral Contraception Study suggested increased mortality rates associated with oral contraceptive use, but later reports with longer follow-up periods suggested that those effects occurred mainly in those who smoked and among older women.

This is a report of the latest mortality findings from the RCGP Oral Contraceptive Study based on up to 39 years of follow-up and nearly 3 times as many deaths as reported earlier.

Study Highlights

The RCGP Oral Contraceptive Study started in 1968 with 1400 general practitioners in the United Kingdom who recruited 23,000 women who were married or cohabiting, mainly white, with a mean age of 29 years, half of whom were prescribed oral contraceptives and the other who had never used the pill.
The GPs provided information on their health status every 6 months; women remained in the study until they left the area, the practitioner left, they died, or had stopped GP follow-up.
35,104 of the original cohort were flagged in the 1970s to be followed up for cancer and death outcomes, even if they were no longer following up with the same GP.
2 datasets were subsequently assembled: one was the full dataset with periods of observation to 2007 or at the time of death, and the other was the dataset for all flagged women younger than 38 years at the time of loss to follow-up when follow-up ended in 1996.
The GP observation dataset included deaths, events, and other information collected until time of death; loss to GPs; or until 1996 when GP follow-up ended, whichever came first.
Deaths were coded according to International Classification of Diseases, Eighth Revision, categories for causes of death including specific cancers; gynecologic cancers; ischemic heart, respiratory, digestive, and other diseases; and violent deaths.
Most deaths were notified by the central registries (75%), and others were notified by the GP or by both sources.
The full dataset contained more than 819,000 woman-years of observation for ever-users and 378,000 woman-years for never-users.
Compared with never-users, ever-users were younger, smokers, had higher parity and social class at recruitment, and were more likely to have used hormone replacement therapy.
In the full dataset, all-cause mortality rate among ever-users was 12% lower vs never-users (adjusted relative risk, 0.8.
There were significantly fewer deaths from all causes in ever-users, including deaths from all cancers; cancer of the large bowel/rectum, uterus, ovaries, or gynecologic cancers combined; ischemic heart disease; and all other diseases.
There was a higher rate of death from violent causes among women in the ever-use cohort.
All-cause mortality rate increased with age and smoking in both ever-users and never-users.
In the youngest age group (< 30 years), ever-users had a 3 times higher mortality rate vs never-users (adjusted relative risk, 2.85).
From age 50 years, however, the risk for any death was lower in ever-users vs never-users in all categories of smoking, social class, and parity.
The overall absolute mortality reduction rate among ever-users was 52 per 100,000 women-years, but this varied by age group (20 excess deaths per 100,000 women-years at age < 30 years, 4 excess deaths at ages 30 - 39 years, 14 fewer deaths at ages 40 - 49 years, 86 fewer deaths at ages 50 to 59 years, 122 fewer deaths at ages 60 - 69 years, and 308 fewer deaths at age 70 years or older).
Median duration of oral contraceptives was 44 months.
No pattern of difference in all-cause mortality was associated with oral contraceptive use for different durations vs never-users.
There was a higher rate of death from violent causes among younger women in the ever-use cohort.
There was an increased rate of death among oral contraceptive users from circulatory disease within 5 to 9 years of stopping the pill, but among those who stopped 10 or more years before, there was no increased risk.
Risk for death associated with the hormonal content of the pill was not examined.
Most pills used had 50 μg of estrogen.
The authors concluded that oral contraceptive use was not associated with increased mortality rates in long-term follow-up.
Clinical Implications

Use of oral contraceptives is not associated with increased mortality rates among women.
Use of oral contraceptives is associated with a reduction in all-cause and cause-specific mortality rates except for mortality rates from violence.

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FDA Orders Two Drugmakers To Stop Selling Unapproved Nitroglycerin Tablets.
New Jersey's Star-Ledger (3/16, Todd) reports that the FDA on Tuesday ordered "Glenmark Generics to stop selling unapproved nitroglycerin tablets for relief from chest pain." The unapproved drugs "are different from approved nitroglycerin tablets in some ways, such as formulation and labeling, but the FDA said it has seen quality and efficacy problems with the unapproved versions." The FDA also "advised consumers that Pfizer sells a version of the product that has been approved by regulators." Kotec Inc. of Arizona also received a warning.
According to the Los Angeles Times (3/16, Healy) "Booster Shots" blog, the FDA gave the two drugmakers "90 days to stop making and selling nitroglycerin tablets for use by heart patients and 180 days to stop shipping those they have made." Reuters (3/17, Richwine, Loganathan) also covers the story.
Regulatory
FDA Warns ISTA Pharmaceuticals About Advertisement For Xibrom Eye Solution.
Dow Jones Newswire (3/17, Favole, subscription required) reports that, in a letter posted to its website and sent to ISTA Pharmaceuticals, the Food and Drug Administration said that a sales advertisement for that company's Xibrom (bromfenac ophthalmic) eye solution was misleading. The agency told ISTA to cease running the advertisement immediately.
Reuters (3/17, Richwine) quotes a portion of the March 10 letter to ISTA in which the FDA said that the advertisement "omits and minimizes important risk information."
"Regulators took issue with marketing material for the drug, 'because it suggests that Xibrom is superior to other drugs in its class when this has not been demonstrated by substantial evidence or substantial clinical experience,'" the Orange County Business Journal (3/16, Lyster) reported. In addition, the letter "took issue with suggestions that Xibrom 'is effective in a broader range of patients and conditions than has been demonstrated by substantial evidence or substantial clinical experience.'"
Alpharma To Pay $42.5 Million To Settle Marketing Suit.
The Wall Street Journal (3/17, Favole, subscription required) reports that the Justice Department said Alpharma Inc. has agreed to settle allegations that it paid physicians to promote and prescribe morphine drug Kadian for $42.5 million. The agreement resolves a whistleblower suit that accused Alpharma of misrepresenting the safety of its drug and paying physicians to prescribe Kadian.

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House Passes Healthcare Reform Measure By 219-212 Vote.
In what media reports and analyses are casting as a historic development and a major win for President Obama, the House Sunday night passed the Senate-approved healthcare reform measure by 219-212. The AP (3/22) notes that after passing the bill, the House proceeded to approve "key changes" to it, "part of a prearranged agreement to guarantee passage of the historic legislation. The changes passed by a 220-211 vote. That bill now goes to the Senate for final approval, where it only requires a simple majority to pass."
Most stories are describing the bill in largely favorable terms -- and the vote as a triumph of the political system as a whole. The vote, reports USA Today (3/22, Wolf, Fritze), "assured that about 32 million Americans will gain health insurance coverage, and millions more will win protections against losing theirs." The Los Angeles Times (3/22, Levey, Hook, Silva, Muskal) reports that "House Democratic leaders proved they could hold the majority caucus together," though "thirty-four Democrats opposed the bill, as did all Republicans." An AP (3/22, Woodward) story observes, "Rarely does the government, that big, clumsy, poorly regarded oaf, pull off anything short of war that touches all lives with one act, one stroke of a president's pen. Such a moment has come."
It was, Bloomberg News (3/22, Litvan, Rowley, Jensen) notes, "the most sweeping US healthcare legislation in four decades," and "the biggest victory yet for...Obama."
The Los Angeles Times (3/22, Nicholas) reports, "Rarely does a president bet everything on a single card, but...Obama did it on healthcare," and "what became clear in the...debate is that Obama is a president with a combative stubbornness, one that was not often visible in his cool, above-the-fray public demeanor."
In a front-page story, the New York Times (3/22, A1, Bernard) reports, "The uninsured are clearly the biggest beneficiaries of the legislation, which would extend the healthcare safety net for the lowest-income Americans." Meanwhile, "for people already covered by a large employer -- most Americans, in other words -- the effect would not be as significant. And yet, just about everyone might benefit from tighter insurance regulations." The Times adds, "There is no question that the legislation should benefit consumers in various ways." In a separate front-page story, the New York Times (3/22, A1, Pear, Herszenhorn) notes that "Democrats hailed the vote as historic, comparable to the establishment of Medicare and Social Security and a long overdue step forward in social justice."
McClatchy (3/22, Doyle) reports that "Pelosi has already made the history books, and now she's written a new chapter in wielding power." The vote, says The Hill (3/22, Cusack), "showed...why she is one of the most powerful Speakers in history." Pelosi "achieved what some thought what was impossible after Scott Brown's victory in Massachusetts two months ago."
McClatchy (3/22, Lightman, Douglas) reports that "within a year, insurers" will "be barred from denying coverage to children because of pre-existing conditions, imposing lifetime limits on coverage and dropping people from coverage when they get sick." The bill also "provides more help with insurance premiums for lower- and middle-income consumers and expands Medicaid funding to states." Politico (3/22, O'Connor) reports that it was "a legislative landmark Sunday night that has eluded generations of lawmakers" -- one that provides a "climatic finale to a yearlong saga that has taken its toll on the president and his party" while securing "a historic win for Obama while providing his party with some much-needed momentum after a long, grueling slog." The Washington Times (3/22, Haberkorn) also notes that "Democrats hailed the vote as one of the most significant change[s] in American social policy since the creation of Medicare in 1965 or Social Security in 1935."

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An Exultant Obama Signs Healthcare Bill Into Law.
The signing of the healthcare reform legislation received very extensive, and overwhelmingly positive, media coverage, much of it casting the event as a historic occasion and as a major triumph for the President and his party. While Republicans continued to appear confident that the new law will be an electoral boon for them this fall, some analysts are now predicting that the win on healthcare gives Democrats new momentum and could change the political dynamic of recent months.
The bill itself is being described in generally positive terms. ABC World News (3/23, lead story, 2:45, Sawyer) said in its lead story last night, devoted to the bill signing at the White House, "As of today, it is the law of the land that every man, woman and child in America will have healthcare coverage." ABC (Tapper) added that Obama "was as happy as we've seen him, perhaps since the inauguration." The CBS Evening News (3/23, lead story, 3:00, Smith) led its broadcast announcing that this is "the closest the nation has ever come to universal coverage," and added that "ecstatic Congressional Democrats treated the President and Vice President like conquering heroes."
Insurance Mandate, Some Tax Hikes Won't Go Into Effect Until After 2012 Election. Politico (3/24, Brown) reports, "Voters will get their first taste of the benefits of health care reform only a few short weeks before the November midterm elections. They won't have to swallow most of the bitter pills until much later -- well after...Obama faces voters again in 2012." Politico adds that matching "the effective dates of key reform provisions against the election calendar" suggests that "Democrats were as focused on writing a legislative overhaul of the health care system as they were on devising a political road map for selling it to voters." The final bill "delays by at least two years the taxes on the insurance and medical device industries, the cap on contributions to flexible savings accounts and the excise tax on so-called Cadillac insurance plans."
The AP (3/24, Loven) reports, "The law's most far-reaching changes don't kick until 2014, including a requirement that most Americans carry health insurance...or pay a fine. To make that a reality, tax credits to help cover the cost of premiums will start flowing to middle-class families and Medicaid will be expanded to cover more low-income people."
Experts Give State Lawsuits Against Healthcare Reform Little Chance Of Success. AFP (3/24) reports, "In a sign of political battles to come, 14 US states filed lawsuits Tuesday challenging the constitutionality of health care reform just moments after President Barack Obama signed it into law." Moreover, "other states are expected to join the fight against the far-reaching reforms which could place huge burdens on state budgets," and "many are also considering legislation to block a provision which requires most people to buy insurance or pay a fine."
Overhaul Expands Medicare-Drug Management. USA Today /Kaiser Health News (3/23, Jaffe) reported, "When Medicare drug coverage took effect in 2006, Congress required health plans to provide medication management, but the rules were so vague that an insurer could comply simply by sending a brochure." The health overhaul, however, requires "an annual medication review and quarterly reassessments. Discussions must be in person, over the phone or via the Internet, and seniors must get a written summary." Notably, many insurers already have enhanced medication-management programs in place. Under the programs, "insurance company representatives -- in most cases, pharmacists -- are required to ask these members about their medications and side effects. They must report any problems to patients' doctors, along with recommended changes such as lowering the dose or replacing or eliminating a drug."

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Research

Potential Hepatitis C Treatment May Be As Effective Current Standard Treatment.

The Wall Street Journal (3/24, Kingsbury) reported that preliminary results from a midstage trial indicate that Zalbin (albinterferon alfa-2b) looks promising as a treatment for patients with genotypes 2 and 3 hepatitis C. In fact, Human Genome Sciences' monthly treatment appears to be just as effective as Roche Holding's Pegasys (peginterferon alfa-2a), according to Reuters (3/24, Dey).
The AP (3/24) pointed out that the "midstage study was conducted by Novartis, which is developing the drug with Human Genome Sciences. It combined the drug with ribavirin in 391 patients with forms of chronic hepatitis C." Notably, Human Genome "has submitted an application for Zalbin dosed every two weeks to the Food and Drug Administration, which is expected to make a decision this fall."

Study Questions Antithrombotic Therapy For Women With Recurrent Miscarriages.

The Los Angeles Times (3/24, Roan) "Booster Shots" blog reported that a study published Wednesday in the New England Journal of Medicine "casts doubt on antithrombotic therapy -- therapy to reduce clotting -- for women with recurrent miscarriages." Investigators "assigned 299 pregnant women to either aspirin and heparin (a blood-thinner), aspirin alone or a placebo," but "stopped" it "early because there were no differences in the miscarriage rates in the three groups. A previous randomized, controlled trial in Scotland also found the therapy is ineffective."

Poniard's Plan To Seek Approval For Picoplatin Stalls.

The AP (3/25) reports that Poniard Pharmaceuticals Inc. announced "it will halt plans to gain regulatory approval for the potential cancer drug picoplatin" following "a mix of study data," including "results showing patients taking picoplatin were more likely to develop two rare blood disorders, thrombocytopenia and neutropenia, than patients taking a standard chemotherapy regimen of treatment." Still, Poniard "plans to focus its strategy for picoplatin in small cell lung cancer, colorectal, prostate, and ovarian cancers."
Reuters (3/24) reports that Lazard Capital Markets analyst Joel Sendek said Poniard will require a partner to develop the medication, and may have to liquidate. The San Francisco Business Times (3/24, Brown) also covers this story.

Researchers Suggest Moving "Beyond" Emergency Contraception.

The Washington Times (3/25, Wetzstein) reports that as "the annual campaign to promote emergency contraception (EC) to sexually active women swung into action" Wednesday, critics say the oral-contraceptive "hasn't lived up to its hype." They point to research that "has shown that it has not dented either pregnancy or abortion rates." Researchers, in the March issue of Perspectives on Sexual and Reproductive Health, suggest "it's time to move beyond EC." Women could be allowed "IUDs (intrauterine devices) when they ask for them, instead of at a subsequent visit," they say. Alternatively, there could be a greater effort "to promote long-lasting-but-reversible contraceptives such as an implant or LNG-IUS (levonorgestrel intrauterine system)."

Antidepressants More Effective Than Placebo In Treating Depression In People With Physical Illness.

Medscape (3/24, Brooks) reported, "Antidepressants are more effective than placebo in treating depression in people with a physical illness, according to" a review published online March 17 in the Cochrane Database of Systematic Reviews. After reviewing "51 randomized controlled trials comparing antidepressants -- mostly tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) -- vs. placebos in a total of 3,603 adults with major depression; adjustment disorder or dysthymia; and a physical illnesses such as stroke, HIV/AIDS, Parkinson's disease, cancer, and chronic obstructive pulmonary disease," researchers found "in 25 studies (1,674 patients) contributing data on short-term response...the odds of response were significantly greater with antidepressants vs. placebo (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.80 - 3.00)."

Bevacizumab May Slow Metastatic Breast Cancer.

MedPage Today (3/24, Bankhead) reported that a meta-analysis of three clinical trials reported at the European Breast Cancer Conference showed "progression-free survival in metastatic breast cancer improved by almost a third in women who received bevacizumab (Avastin) in addition to chemotherapy as first-line treatment." The data "showed a trend toward improved overall survival with chemotherapy plus bevacizumab compared with chemotherapy alone. Response rate increased by 85% in women who received the targeted agent."