Good morning Mr. Chairman, Ranking Member Buyer and Members of the Committee.

My name is Ponni Subbiah.  I am a medical doctor and a Vice President in Medical Affairs at Pfizer.  I am responsible for the medical and scientific activities for products in the Urology/Respiratory area, which includes Chantix.  On behalf of Pfizer, thank you for the opportunity to speak with you today.  I would like to briefly address the following areas: the global epidemic of tobacco addiction and its impact on public health; the role of Chantix in helping patients stop smoking; the clinical trial process at Pfizer; how Pfizer monitors drug safety; and, finally, the recent updates to the Chantix label. 

The World Health Organization has described tobacco use as the leading preventable cause of death.   Worldwide, approximately 1.3 billion people currently smoke cigarettes.1  In the U.S. alone, more than 438,000 deaths are attributable to smoking each year.2  More people die from smoking annually than inhabit the city of Miami, Florida.3  In fact, cigarette smoking is a risk factor for six of the eight leading causes of death in the world – including heart disease, stroke, lung disease such as emphysema, tuberculosis, and lung cancers.1  Health care costs from smoking-attributable diseases are $75.5 billion annually as per the 2004 Surgeon General’s report.4

It is important to understand that, for most people, smoking is not a lifestyle choice or habit, but rather an addiction to nicotine.  Nicotine is a highly addictive drug - as addictive as heroin or cocaine. Smokers become physically and psychologically dependent on nicotine.  Less than 7% of  smokers are able to quit on their own.5  Therefore, medications and other therapeutic options are needed to assist smokers who are motivated to quit.    Quitting smoking, with or without treatment, is associated with nicotine withdrawal symptoms, which are both physical and mental and may include irritability, anger, depressed mood and weight gain.  Quitting smoking has also been associated with the exacerbation of underlying psychiatric illnesses.6  It is important to assess the benefits and risks of smoking cessation treatments in the context of this setting. 

In the United States, currently 20.8% of the population in general smoke cigarettes.7  By comparison the smoking rate in the VA population is 33%.8 Of interest to this hearing, there is a strong link between smoking and a range of psychiatric disorders. A study by Harvard Medical School showed that 35 - 41% of people with mental illness smoke.9  Smoking prevalence rates are 50 - 70% 10, 11 in patients with major depression and over 80% in patients with schizophrenia.11  The smoking rate in post traumatic stress disorder (PTSD) patients ranges from 45 - 60%.12, 13  

Chantix is the first non-nicotine based medicine developed specifically for smoking cessation and the first prescription aid to smoking cessation approved by the FDA in nearly a decade.  It is currently approved in 74 countries and is designed to bind at the same receptor in the brain as nicotine, which allows it to reduce the urge to smoke, while at the same time blocking the effects of nicotine.14 Chantix has been demonstrated to be more efficacious than placebo and Zyban (another popular smoking cessation treatment) in two clinical trials.  To date, Chantix has been prescribed to approximately 7.5 million patients worldwide, 5.6 million of those in the U.S. 

Chantix is not a treatment that is used over a prolonged period of time.  Rather, physicians should prescribe Chantix for 3 months for their patients who wish to quit smoking.  For those patients who successfully quit with Chantix by the end of the 3 months, an additional 3 months of Chantix is recommended to help them remain smoke free.14 

Chantix was studied in a comprehensive clinical trial program involving more than 5,000 patients over a span of 10 years.  The studies conducted during development of a drug for approval are done in order to fully characterize the unique properties of a medicine.  The FDA will approve a medicine for use only when its benefits outweigh the risks.  Even after a medicine enters the market, and throughout the lifecycle of the product, Pfizer strives to enhance its knowledge regarding the safety and efficacy of its products through ongoing research in order to continually assess the benefit/risk profile.  This includes information not only on risks but also on the important benefits that these medicines may have, especially in specific subpopulations.    The benefits and risks that need to be considered will vary between different disease areas as well as between individual patients.  Thus, consideration of benefits and risks of medicines is a critical component of the dialogue that needs to occur between patients and their doctors.

Gathering data to continuously inform the benefit/risk assessment is accomplished through various means, including conducting clinical trials and epidemiological studies.   Gathering this information requires Pfizer to work with outside researchers in a variety of ways such as getting scientific input and involving external experts in Pfizer’s clinical study program for a medicine.  When clinical trials are conducted, there are various mechanisms in place designed to protect patients from harm.  These include independent Institutional Review Boards (IRBs), which are designed to assure that appropriate steps are taken to protect the rights and welfare of patients.  Patients must also give their informed consent prior to participating in a study.

Prior to a medicine’s approval, Pfizer is the sponsor of, and responsible for, the clinical trials involving the medicine.  The company contracts with independent researchers to conduct studies according to international standards and FDA’s good clinical trial practice (GCP) regulations. After the medicine is approved, there may be studies done that are not sponsored by Pfizer, but may be supported by the company through the provision of grant funding or free supplies of Pfizer medicines for independent investigator research (IIR) to advance scientific knowledge and understanding.  However, Pfizer is not involved in the design, conduct or publication of an IIR study. 

There are also clinical trials of Pfizer medicines, such as the trial that is the subject of this hearing, that are conducted independently of Pfizer.  Once a medicine is available on the market, any researcher can obtain the medicine and conduct studies without the involvement of Pfizer.  These studies may be funded from non-Pfizer sources such as academic institutions or the NIH. 

The Pfizer drug safety surveillance system is designed to continuously gather and analyze reports received about patient experiences with our products after they have become available in the market. These adverse event reports are routinely shared with the FDA and other regulators as required.  Based on clinical study data and post-marketing reports, we work with regulators on a continuing basis to effectively communicate to patients and healthcare professionals any change in the benefit/risk profiles of our medicines.  The primary mechanism of communicating changes in a medicine’s benefit/risk profile is the product labeling.  It  is common for the label to be revised numerous times in a product’s lifecycle.  In fact, in 2007 there have been over 500 FDA approved safety related labeling changes across various prescription medicines in the U.S.  Pfizer’s primary goal is to communicate to both physicians and patients what is known about the benefits and risks so that doctors and patients can decide together whether a particular medicine is the best treatment option.

With regard to Chantix, there have been adverse event reports of certain neuropsychiatric symptoms, including depressed mood, agitation, changes in behavior, thoughts of suicide and suicidal behaviors, in patients attempting to quit smoking with Chantix.  The report of an adverse event does not necessarily mean there is a causal relationship between the product and the event and, in the case of Chantix, a causal relationship between these reports and the use of Chantix has not been established.  However, in some reports related to Chantix, a causal relationship could not be excluded.  In November 2007 Pfizer worked with the FDA to update the Chantix label to reflect these reports.  Additional label updates were made in January and May 2008, respectively, to put this information in the Warnings section of the label to heighten awareness and to provide further guidance to physicians and patients about these symptoms. The current label advises that a patient should stop taking Chantix and contact their healthcare provider immediately if agitation, depressed mood, or changes in behavior that are not typical for them are observed or if the patient develops suicidal ideation or behavior.

Pfizer communicated these label updates to physicians, study investigators and other health care professionals through various routes including product labeling, written communications, website updates (e.g. PfizerPro.com, Chantix.com) and communications from our sales representatives.  Patients have access to this information through their health care provider as well as through the Chantix website (Chantix.com).

Pfizer reviews the benefit/risk profile of all our products, including Chantix, on a continuing basis.  Based on our review of the available safety information, including the adverse event reports received to date, we believe the Chantix label accurately reflects the product’s efficacy and safety profile, thereby facilitating appropriate use by physicians and patients.  In particular, full awareness and understanding by both physicians and patients of the neuropsychiatric symptom related labeling, highlights the key role that doctors and patients can play in managing and mitigating the potential risks, so that the important benefits of Chantix as an aid to smoking cessation can be realized when appropriate.      

There are few things that provide greater health benefits than quitting smoking.  Patients who smoke cigarettes should be encouraged to seek support from a health care professional and counseled to quit.  Health care providers should discuss the risks of smoking, the health benefits of quitting smoking, and the benefits and risks of available treatment options including Chantix.  It has been reported that nearly 70% of smokers want to quit, although as indicated earlier, fewer than 7% of those who try are able to quit on their own.5  Given the devastating health effects of smoking, it is essential to have treatment options available to help smokers break free of nicotine addiction and stop smoking.

Thank you.  I look forward to answering any questions you may have.

 References

1. World Health Organization. WHO Report on the Global Tobacco Epidemic, 2008: The MPOWER package. Geneva: WHO; 2008.

2. Centers for Disease Control and Prevention. Annual Smoking-Attributable Mortality, Years of Potential Life Lost, and Productivity Losses --- United States, 1997--2001. MMWR. 2005;54(25):625-628.

3. U.S. Census Bureau. Annual Population Estimates 2000 to 2007. 2007.

4. Centers for Disease Control and Prevention. Smoking-attributable mortality, morbidity, and economic costs (SAMMEC): adult and maternal and child health software. Atlanta, GA: US Department of Health and Human Services, CDC; 2004.

5. National Institute on Drug Abuse. Nicotine Addiction. NIH Publication 01-4342. Bethesda, MD: National Institute on Drug Abuse; 2001.

6. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th Ed, Text Revision (DSM-IV-TR). Washington, DC; 2000.

7. Centers for Disease Control and Prevention. Cigarette smoking among adults--United States, 2006. MMWR. Nov 9 2007;56(44):1157-1161.

8. McKinney WP, McIntire DD, Carmody TJ, Joseph A. Comparing the smoking behavior of veterans and nonveterans. Public Health Rep. May-Jun 1997;112(3):212-217; discussion 218.

9. Lasser K, Boyd JW, Woolhandler S, Himmelstein DU, McCormick D, Bor DH. Smoking and mental illness: A population-based prevalence study. JAMA. Nov 22-29 2000;284(20):2606-2610.

10. George TP, Krystal JH. Comorbidity of psychiatric and substance abuse disorders. Current Opinion in Psychiatry. 2000;13(3):327-331.

11. Hughes JR, Hatsukami DK, Mitchell JE, Dahlgren LA. Prevalence of smoking among psychiatric outpatients. Am J Psychiatry. Aug 1986;143(8):993-997.

12. Beckham JC, Kirby AC, Feldman ME, et al. Prevalence and correlates of heavy smoking in Vietnam veterans with chronic posttraumatic stress disorder. Addict Behav. Sep-Oct 1997;22(5):637-647.

13. Fu SS, McFall M, Saxon AJ, et al. Post-traumatic stress disorder and smoking: a systematic review. Nicotine Tob Res. Nov 2007;9(11):1071-1084.

14. Chantix (varenicline) [US prescribing information]. New York, NY: Pfizer, Inc.; May 2008.