Ensuring Confidence in the Safety and Quality of Our Products

Nothing is more important to Merck than the quality and safety of our medicines and vaccines. We dedicate millions of dollars each year and extensive resources to ensuring the safety profiles of our products are well characterized. The President of Merck Research Laboratories (MRL) has ultimate responsibility for the analyses and interpretations of safety data and safety-related decisions. In addition to the physicians and nurses we employ to conduct clinical trials, our pharmacologists analyze compounds chemically to determine potential effects in people, and epidemiologists assess the prevalence of potential risks in a population.

The Worldwide Withdrawal of VIOXX

On September 30, 2004, Merck announced a voluntary worldwide withdrawal of VIOXX® (rofecoxib), our arthritis and acute pain medication. Merck took this action because we believed it best served the interests of patients.

Although we believed it would have been possible to continue to market VIOXX with labeling that would incorporate the new data, given the availability of alternative therapies and the questions raised by the data, we concluded that a voluntary withdrawal was the most responsible course of action.

In the several years after the withdrawal of VIOXX, VIOXX has been the subject of litigation. However, after prevailing in the majority of cases that were brought to trial, Merck entered into an agreement to resolve the majority of the U.S. product liability lawsuits related to VIOXX. More than 99 percent of eligible U.S. claimants have initiated enrollment in the program.

The Company has a dedicated Vioxx Information Center that contains all major Company communications and other resources on the matter.

We build on this work by engaging with regulatory authorities and independent scientific and medical groups and individuals, often at leading universities and medical schools, to collect, investigate and evaluate information about the effects of medicines and vaccines. We do this not only before a product can be approved but also after a product has begun to be prescribed.

Safety Monitoring

Merck has an efficient global system of pharmacovigilance. Our global pharmacovigilance teams within MRL are responsible for the safety evaluation of our medicines and vaccines. In parallel, at the country level, local pharmacovigilance teams at our subsidiaries worldwide are responsible for ensuring that safety information is collected and reported to our Headquarters pharmacovigilance staff and to local regulatory authorities.

Clinical Trials

We assess the safety of our products in clinical trials over many years before our products are approved. We disclose results from our clinical trials in patients irrespective of the outcome. Click here for more information on clinical trials.

Post Marketing Studies

Merck continues to research the effectiveness and safety profiles of our products on an ongoing basis. We conduct several types of studies after approval:

Post Marketing Studies

Post-approval studies on new indications: Some drugs may be effective for more than one indication. For example, an oncology product can be developed to treat several types of cancer. In such cases, a clinical trial must be conducted to determine the safety and efficacy of the drug in each new patient population.
Commitments to Regulatory Authorities: For some products, regulatory authorities require that companies conduct additional studies after the product is approved. The study could be required for multiple reasons including to obtain further information on the safety of the product. Merck works closely with regulatory authorities to design a study that will fulfill the specific requirement.
Epidemiology studies: Merck has a long history of working closely with external experts in pharmacoepidemiology to understand the types of patients utilizing our products as well as examine the effectiveness and safety profiles of many of our marketed products as they are used in clinical practice in several population-based health care systems.
Pregnancy Registries: For some products, Merck has active data collections in systems, which can facilitate the early detection of teratogenicity and other serious adverse experiences in patients who inadvertently or purposefully use a drug during pregnancy. Useful information about the outcome of exposure in pregnancy can best be obtained by the careful collection and analysis of postmarketing surveillance data. Reports of the aggregate data in each Registry are updated annually.

Adverse Experience Reporting (AER)

Questions About Merck Products in 2008

During 2008, post-marketing reports of adverse events drew interest from the media on the safety of GARDASIL, our vaccine to help prevent cervical cancer. Merck continues to evaluate all safety data in the context of its own post-marketing adverse experience database as well as its ongoing clinical trial database and provides post-marketing reports to regulatory authorities worldwide. In December 2008, after an updated review of all available safety data, the CDC reinforced their continued recommendation for vaccination with GARDASIL.¹

Since the introduction of SINGULAIR in 1998, the Company has updated the post-marketing section of the prescribing information to communicate a range of adverse events reported with post-marketing use of the drug, including neuropsychiatric events. Merck will continue to work with the FDA to revise the prescribing information for SINGULAIR in the United States to include a precaution related to those events. Merck is confident in the efficacy and safety of SINGULAIR, which has been prescribed to tens of millions of patients with asthma and allergic rhinitis since its approval.²

After a product has been approved and is being prescribed to patients, regulatory authorities require manufacturers to report adverse experience information received from any source – domestic or foreign. These sources can include clinical trials, health care providers, patients, published literature and epidemiological or observational studies. Our staff of global pharmacovigilance professionals ensure adverse experience information is entered into our global AER database and is submitted to regulatory authorities in accordance with country specific regulations.

To report an adverse experience to regulatory authorities, we need minimal information: the name of a Merck medicine or vaccine involved, an adverse experience, an identifiable patient and an identifiable reporter.

In addition to submission of individual adverse experience reports to regulatory authorities, either within 15 days or periodically, we also file certain periodic reports that aggregate information for as long as we market a product.

Over time, rare adverse experiences may be detected as more patients use a product. Additionally, an adverse experience may be more frequent or more intense than initially observed in clinical trials. Our safety teams, which include physicians and epidemiologists, review post-marketing data and determine whether actions need to be taken with reference to the evolving safety profile of our products.

Safety Matters Initiative

In late 2007, Merck senior leadership launched the SafetyMatters initiative to investigate potential enhancements to our already robust approach for identifying and evaluating health outcomes of interest (HOIs) in connection with our marketed products. The goal of the SafetyMatters initiative is to explore and implement appropriate use of emerging technologies and methods for HOI identification and evaluation, and thereby further enhance post-licensure monitoring and evaluation of our marketed products.

Product Label Reviews

Ongoing oversight and monitoring of our product labels is a major focus of our safety efforts. Our label review teams monitor information on our products and work with our product safety teams to develop or update product labeling. We communicate relevant information on an ongoing basis to regulatory agencies worldwide.

Observational Medical Outcomes Pilot (OMOP)

The Observational Medical Outcomes Pilot (OMOP) initiative is a partnership between PhRMA and FDA to comprehensively identify and assess the optimal applications of large claims and electronic health record databases for the purpose of the continuing evaluation of the benefit/risk profiles of marketed drugs. This collaboration has been in development since late 2006, and was formally initiated in August 2008. Merck has been a principal contributor to this effort since the early planning stages, and will continue to actively support the many scientific method research projects arising from this collaboration over the next two years. OMOP is complementary to our internal effort, the SafetyMatters initiative. We continue to explore synergies and linkages between OMOP and SafetyMatters to establish standards for the use of modern epidemiology data sources and analytic techniques to evaluate the benefits and risks of our products.

Training

Employees responsible for monitoring and reporting adverse experiences undergo rigorous training. New MRL employees, including all contract personnel working in areas related to clinical research, undergo training on Merck's adverse experience policies and procedures when they join the company. All MRL employees are encouraged to complete the training.

Communicating About Product Risks

Our information leaflets in our product packaging contain information on possible side effects and, if appropriate, how to avoid some potential problems. We include contact details for patients, care givers and health professionals to report adverse experiences in the United States on our corporate website. Outside the United States, adverse events are reported according to local laws and practices.

Depending on label changes and their context, in consultation with regulatory agencies we may determine that more extensive communications may be appropriate. In such cases, we work with regulatory authorities to contact health care professionals in a timely manner to communicate these findings to patients through appropriate mechanisms. This might include such activities as “Dear Doctor” letters and sometimes media releases.

REPORTING AN ADVERSE EXPERIENCE IN THE U.S.

To speak with a Merck health care professional about Merck products, or to report an adverse experience with a specific Merck product, please call the Merck National Service Center at 800-444-2080. The Merck National Service Center is pleased to assist you Monday through Friday from 8 AM to 7 PM ET. Adverse experiences and product-related emergencies can be reported at any time by dialing:
800-444-2080.

Consistent Product Quality

We strive consistently to maintain strict quality standards that meet current Good Manufacturing Practices regulations in our manufacturing operations and insist on equivalent standards from our suppliers that make active pharmaceutical intermediates and finished pharmaceuticals. For more information on our product quality efforts, click here.

Merck & Co., Inc., Whitehouse Station, NJ, USA, and Schering-Plough Corporation, Kenilworth, NJ, USA, are now one company. We have combined our global operations under the name Merck & Co., Inc. We are working to update our corporate responsibility Web site to reflect our new, combined, global organization.