Clinical Trials

Safety in Research and Development

Delivering a medicine from the laboratory to the patient involves rigorous discovery and development. Abbott is committed to meeting the highest standards of clinical practice in our research. This includes safeguarding the volunteers and patients who participate in clinical trials, as well as ensuring the safety of all products that we bring to market through safety testing before and after launch.

Biomedical research often raises ethical questions about the conduct of clinical trials, the use of new technologies, animal welfare practices and other matters. We abide by national and international regulations and standards, and enforce our own high standards in all research endeavors.

The safety of our clinical trial subjects is of utmost importance, and we take numerous steps to assure that our high standards of quality, safety and transparency are upheld at all stages and in all countries where we conduct trials.

There are three distinct phases of clinical trials. Phase I is conducted on a relatively small number of healthy volunteers to determine whether the drug candidate works in humans as it did in animals and computer models, as well as to obtain information on safety and dosage. Phase II involves a larger number of patients and continues to evaluate the safety and efficacy of the drug, often experimenting with different amounts and dosing frequencies. Phase III is the final, pivotal phase of clinical trials required by government regulators before making the drug widely available through prescription. Regulators have highly specific guidelines for clinical trials, which typically involve hundreds or thousands of patients.

Clinical trials on human subjects are a critical step in bringing safe, effective and correctly dosed medicines to patients. Safety of study subjects is always Abbott's highest priority, and we take a number of steps to assure that our high standards of quality, safety and transparency are upheld at all stages and in all countries around the world where we conduct trials. We have standard operating procedures in place for all employees involved in conducting trials, and they receive dedicated training on these procedures.

Informed consent is crucial for both the safety of participants and the success of trials. Healthy volunteers and patients who are interested in participating in our clinical studies engage in a full discussion of the process with clinical professionals and undergo an appropriate medical screening before entering the trial. Informed consent documentation is drafted in language that's easy for patients to understand and is also translated into different languages if required, to make sure trial subjects have the information they need to make an educated decision on whether to take part in the trial.

Trials are subject to internal as well as independent external scrutiny at every stage. Abbott's internal ethics committees review protocols, and data-monitoring committees make sure data is fairly presented and appropriately shared. Additionally, we work with independent review boards to make sure our studies meet local, national or international guidelines.

Procedures and Training

We have rigorous operating procedures and training for all employees involved in conducting trials, and we take numerous steps to ensure that high standards of quality, safety and transparency are upheld.

Abbott studies are reviewed by independent external review boards to make sure our studies meet local, national or international guidelines. These independent review boards also check the informed consent document. Additionally, studies may be reviewed by an Independent Data Monitoring Committee to assess safety data and to recommend whether to continue, modify or stop a trial.

Abbott is committed to being transparent about the clinical trials we sponsor. We recognize that there are important public health benefits to making clinical trial information available to health care providers, patients, and the public. We voluntarily abide by the PhRMA Principles on Conduct of Clinical Trials and Communication of Clinical Trial results.

Our registrations and results disclosure adhere to all relevant state and federal laws.

In addition, Abbott respects the influence of the following organizations regarding registrations and results disclosures. However, where policies of these organizations conflict with the above laws, Abbott will defer to the laws.

• WHO Technical Consultation on Clinical Trial Registration Standards (April 2005)
• Joint Position Statement on the Disclosure of Pharmaceutical Clinical Trial Information (November 26, 2008)
• International Council of Medical Journal Editors (ICMJE), Uniform Requirements for Manuscripts

Abbott registers all applicable clinical studies, regardless of outcome, in a publicly accessible clinical trials registry (www.ClinicalTrials.gov). For drugs, we register all phase 2–4 interventional trials. For medical devices, we register prospective interventional clinical studies of health outcomes, except feasibility studies, and FDA-designated pediatric post-marketing surveillance studies. Registration information is provided according to the laws and policies mentioned above.

Abbott discloses the results of all applicable clinical trials, regardless of outcome, in a publicly accessible clinical trials results database (www.ClinicalTrials.gov). For pharmaceuticals, we report results for all phase 2–4 interventional trials for our approved products. Consistent with the Joint Position Statement on the Disclosure of Pharmaceutical Clinical Trial Information, we also report the results of any exploratory pharmaceutical clinical trials if we deem the findings to have significant medical importance (e.g., an important safety finding). For medical devices, we report results for prospective interventional clinical studies of health outcomes, except for feasibility studies. In addition, we post results for FDA-designated pediatric post-marketing surveillance studies of medical devices.

Working with Research Partners

Much of our clinical trial work around the world is conducted in partnership with contract research organizations (CROs). It is critical that all CROs commissioned by Abbott meet our high standards of clinical trial conduct, particularly on subject safety. There are multiple procedures in place to ensure that CROs understand and conform to all Abbott's standards, and we perform regular reviews of all CRO conduct. Abbott employees who work with CROs receive training and consult company policies in this area, including on the selection and monitoring of CROs.

Trials in Developing Countries

Increasingly, clinical trials are being conducted in developing and emerging regions. In these countries, as everywhere in the world, we abide by the Helsinki Declaration, World Health Organization Good Clinical Trials Standards and Abbott policies to ensure the highest standard of ethics in conduct of clinical trials.

Clinical Trials Transparency

Abbott is committed to being transparent about the clinical trials we sponsor. We recognize that there are important public health benefits to making clinical trial information available to health care providers, patients and the public. Abbott is committed to registering all applicable clinical studies regardless of outcome on the publicly accessible clinical trial registry www.ClinicalTrials.gov. To date, Abbott has registered over 150 trials initiated under our sponsorship and additionally independent investigators have registered over 100 trials designating Abbott as a collaborator.

Clinical Trial Registration

No later than 21 days after the initiation of patient enrollment, Abbott lists all studies in serious and life-threatening diseases that investigate primary or secondary efficacy endpoints, in compliance with Section 113 of the 1997 Food and Drug Administration Modernization Act.

These registrations will adhere to the compliance specified by the following laws and organization standards: Section 113 of the FDA Modernization Act of 1997 (FDAMA), WHO Technical Consultation on Clinical Trial Registration Standards (April 2005), and the Joint Position Statement on the Disclosure of Clinical Trial Information endorsed by PhRMA and IFPMA in 2005.

Consistent with the preceding standards, the following registration information will be provided: unique trial number, trial registration date, secondary identifiers, sponsors, collaborators, brief title, official title, human subjects review, brief summary, study phase, study type, recruitment status, study start date, study design, outcome measures, intervention type and name, condition, inclusion and exclusion criteria, target sample size, central contact and study officials. For some studies, additional fields may also be disclosed.

Following these standards, Abbott registers clinical trials active on, or initiated after, July 1, 2005.

Clinical Trial Results Disclosure

Abbott discloses the results of all clinical trials regardless of outcome, other than exploratory studies, in a publicly accessible clinical trials results database (www.ClinicalStudyResults.org), on any pharmaceutical product that is approved for marketing and is sold in at least one country.

Abbott also discloses trial results from exploratory studies if they are deemed to be of significant medical importance. Abbott posts results within one year after the product is first approved and sold in any country, unless the posting would compromise publication in a peer-reviewed journal or contravene national laws and regulations. Results of efficacy and safety registration trials active on or after October 2002 will be disclosed once the product is approved for marketing in at least one country.

Global Initiatives

In a constantly changing regulatory environment, we seek to engage with all stakeholders to ensure that we are not only staying abreast of regulation but also proactively moving the debate forward. We continue to work with industry partners, trade associations, the U.S. Congress, regulators, international health organizations, academics and patient groups to develop a global framework for registration and results disclosure. We also actively participate in trade association activities aimed at increasing clinical trial transparency.

The International Federation of Pharmaceutical Manufacturers & Associations (IFPMA) Portal helps users access information about ongoing clinical trials and the outcomes of completed trials through custom searches. In addition to English, the IFPMA Portal allows users to search in the French, Spanish, German and Japanese languages, making it a unique and valuable international tool.

The Portal allows access to, and search capabilities for, two broad types of information:

1) Listings (registries) of ongoing clinical trials throughout the world, providing access to basic information, such as brief title, description in lay terms, trial phase, trial type (e.g. interventional), trial status, trial purpose (e.g. treatment, diagnosis, prevention), intervention type (e.g. drug, vaccine), condition or disease, key eligibility criteria (including gender and age), location of trial and contact information; and

2) Links to the results of completed clinical trials, which are made available in a standard, nonpromotional, summary format by various online databases.

This search portal is provided by IFPMA on behalf of its member companies and associations. The portal offers a single entry point for the public to access comprehensive information on ongoing clinical trials (registry) and results of completed trials (database).

Publishing Clinical Trial Results in Journals

One way we present a full picture of clinical trial results to stakeholders is through published manuscripts in peer-reviewed journals. Within the industry, there is ever-increasing scrutiny of scientific publication integrity, and questions have recently arisen about improper influence on journal articles by pharmaceutical companies. A draft Abbott publication policy, expected to be fully approved in 2008, provides guidance for all employees on issues such as criteria for authorship, acknowledging medical writers and other contributors, access to data, and disclosing conflict of interest and clinical trial sponsorship.

The goal for this policy is to establish a corporate standard to ensure that Abbott develops publications in a consistent and transparent manner, applying the highest ethical standards.