Global Standards for Interventional Clinical Studies
1. Purpose & Scope
- The purpose of this clinical and medical controlled document (CMCD) policy is to describe the requirements for the conduct of all Pfizer-sponsored interventional clinical studies.
- Compliance with this policy ensures Pfizer-sponsored interventional clinical studies respect the rights and welfare of study participants (i.e., healthy volunteers, subjects, patients and others) and that those clinical studies are designed and conducted in accordance with the highest scientific and ethical standards as well as regulatory requirements. The term policy will be used throughout the remainder of this CMCD policy.
This policy applies to:
- All Pfizer-sponsored interventional clinical studies that are approved on or after the effective date of this policy.
- Pfizer colleagues who are involved in activities related to the policy, as well as to those parties with whom Pfizer contracts (e.g., contract research organizations, vendors or consultants) to perform such activities, unless Pfizer has agreed that such parties may follow their own processes with respect to these activities.
- Research and business units as well as the functional lines responsible for clinical and medical activities including research, development, regulatory, pharmacovigilance and product quality.
Requirements for the Pfizer Ethical Research Committee (PERC) do not apply to the following studies:
- Pfizer Consumer Healthcare
- Investigator-Initiated Research (IIR)
- Non-Interventional studies or
- Studies conducted in a Pfizer Clinical Research Unit
2. Terms, Acronyms & References
Terms used in this policy that are in the CMCD Global Glossary are hyperlinked upon first occurrence. Acronyms can be found in the CMCD Global Acronyms List . References can be found in the CMCD Global References List . All lists can be found on the eSOP portal.
3. Policy Statements
All Pfizer-sponsored interventional clinical studies are conducted in accordance with local laws and regulations, as well as relevant international standards including:
- International Ethical Guidelines for Biomedical Research Involving Human Subjects issued by the Council for International Organizations of Medical Sciences (CIOMS 2002)
- International Conference on Harmonisation Good Clinical Practices (ICH-GCP) Guidelines
- Ethical principles set forth in the Declaration of Helsinki (World Medical Association 2008)
- United States Belmont Report (1974)
Pfizer Corporate Policies and Procedures including Corporate Procedure 215 International Anti-Bribery and Anti-Corruption Procedure; Worldwide Research & Development (WRD) Policy 201 Anti Corruption, Global Policy on Interactions with Healthcare Professionals (GPIHP) and External Funding All Pfizer-sponsored interventional clinical studies will be conducted in accordance with the principles and procedures described in the Pfizer Human Research Protection Program (HRPP). (See Appendix 1 )
All Pfizer-sponsored interventional clinical studies in patients must be responsive to the healthcare environment of the country or countries where the research is conducted. Social and cultural considerations, and needs in countries that lack established infrastructure for human subject protection, may require additional measures to ensure appropriate protection and respect for the rights, privacy and welfare of study participants.
Informed consent , risk/benefit assessment, qualification of study team members, and the selection of study participants for research will conform to all CIOMS and ICH guidelines, and will be consistent with the principles set forth in the Declaration of Helsinki and the U.S. Belmont Report as well as any local legal and regulatory requirements.
The clinical lead responsible for the study, along with the study team, design Pfizer-sponsored interventional clinical studies and ensure they are conducted in accordance with this policy and Pfizer standards.
In addition to the deviation process in ADM01-GSOP Model for Controlled Clinical and Medical Documents SOP, prospective deviations to this policy require final approval by the Chief Medical Officer (CMO).
The Document Owner Group is responsible for submitting Trial Master File (TMF) required documents to the TMF in accordance with the CT01-GSOP-RF01 TMF Document List, the authoritative source for TMF information.
3.1 Risk/Benefit Considerations
All Pfizer-sponsored interventional clinical studies must have a favorable risk/benefit ratio (e.g., the known or foreseeable risks to the study participants must be justified by the expected benefits, direct or indirect), and must be designed and conducted to maximize the benefit and minimize risks. The clinical lead is responsible for:
- Ensuring that the study design is scientifically valid to obtain the expected knowledge and that the design does not expose the study participants to unnecessary risk. Determining whether risks to participants are minimized by using procedures consistent with sound research design, whether risks to study participants are reasonable in relation to anticipated benefits and the importance of the knowledge expected to result.
- Assessing the risk/benefit ratio before the protocol is submitted to the relevant IRB/IEC.
- Monitoring the risk/benefit ratio while the study is ongoing.
- Taking prompt action to safeguard the rights and safety of study participants.
The aforementioned is managed in accordance with GCP and Global Pharmacovigilance (PV) legislation and includes the collection and reporting of serious and non-serious adverse events to ascertain if the risks are determined to outweigh the benefits of continued participation and permit the clinical study to remain ongoing.
3.2 Ethical Review
A qualified IRB/IEC must review and approve Pfizer-sponsored interventional clinical studies before the study is conducted. The review may be conducted by a central IRB/IEC, as well as by local IRB/IECs that review proposed research for a specific research organization or for clinical study sites.
Central United States (US) IRB must be accredited by the Association for the Accreditation of Human Research Protection Programs (AAHRPP) according to CT12 POL Interactions with Institutional Review Boards and Independent Ethics Committees .
According to GCP and local regulations, IRB/IECs engaged to review Pfizer studies must be independent from Pfizer and be composed of members who have appropriate medical and scientific qualifications, experience, and are knowledgeable about the community where the study will be conducted.
- Pfizer-sponsored interventional studies involving the use of an investigational product must be reviewed by an IRB/IEC that is accredited by AAHRPP. If the IRB/IEC providing review for the protocol is not AAHRPP accredited, the protocol must also be reviewed by the Pfizer Ethical Review Committee (PERC).
Study participants may not be enrolled in Pfizer-sponsored interventional clinical studies until written authorization is received from the IRB/IEC. In addition, study participants may not be enrolled prior to authorization from appropriate regulatory or official governmental bodies from the country in which the study will be conducted, as prescribed by local laws. In those countries where the IRB/IEC does not provide written authorization, study participants may only be enrolled once the IRB/IEC review period has expired and provided that the IRB/IEC has not issued any negative comments either to Pfizer or to the investigator.
3.3 Protocol Eligibility Criteria
Protocols must define the eligibility criteria (i.e., protocol inclusion and exclusion criteria) for the study, based on medically sound criteria and ensure that the study population is scientifically appropriate. All study participants must satisfy all of the eligibility criteria and all study-specific procedures. Assessments must be performed as described in the protocol. Prospective deviations from the protocol inclusion/exclusion criteria are strictly prohibited. Diversity in clinical research (e.g., including diverse racial, gender, ethnic populations) will be sought as much as possible, as well as diversity among the clinical investigators and staff retained to conduct the study.
Interventional clinical studies involving children, pregnant women, geriatric patients and other vulnerable populations must be responsive to the health needs of these populations and be justified by the potential benefit to study participants or to the expected knowledge to result.
3.4 Informed Consent
Study participants may only be enrolled after providing their voluntary informed consent. Investigators involved in Pfizer-sponsored interventional clinical studies must ensure that study participants have adequate understanding of the study. Informed consent must be documented in writing as part of the informed consent process in accordance with CIOMS Ethical Guidelines, in accordance with the principles set forth in CT05 – Informed Consent SOP and local legal requirements. The informed consent needs to include clear explanations of the purpose of the study, the risks and expected benefits associated with participation in the study and the right of the study participant to refuse to participate in the study at any time.
The permission of a legally-authorized representative, in accordance with applicable local law, is required for members of vulnerable populations who are not capable of giving informed consent (e.g., pediatric participants and other decisionally-impaired participants). Such study participants must be afforded the opportunity to provide or withhold their assent, whenever possible.
The procedures for obtaining voluntary informed consent must be tailored to meet local laws (including but not limited to applicable data privacy laws) customs and culture but may not diminish or compromise the rights of the proposed study participant. Pfizer and its representatives must work with the study investigators, ethics committees, local health authorities or community representatives, where appropriate, to ensure the appropriateness of the informed consent process is consistent with Pfizer standards.
3.5 Standard of Care and Use of Placebo Controls
Where Pfizer-sponsored interventional clinical studies involve control groups, the control must be either an established effective treatment that is medically and ethically appropriate for the study or, where appropriate, a placebo. Placebo controls may only be used in Pfizer-sponsored interventional clinical studies where:
- there is no established effective treatment, or
- withholding an established effective treatment would expose study participants to, at most, temporary discomfort or delay in relief of symptoms; or
- use of a placebo control would not add any risk of serious or irreversible harm to the study participants.
In all cases, the IRB/IEC must review and approve the appropriateness of the proposed treatment for the control group.
3.6 Study Placement
Pfizer-sponsored clinical research in patients must be relevant to the host country's health needs. In order to be conducted in a particular country, the clinical research in patients must have the intention and potential to benefit that country's population.
Clinical studies in patients may only be placed in countries where:
- the investigational product is already approved for the indication under study and it is available or there is intent to make it so (e.g. phase 4 studies) or
- Pfizer intends, at the time of study initiation, to obtain approval for and make the investigational product available, if it is proven to be safe and effective (e.g. phase 2 & 3 studies)
- the product is already approved and available in that country for an alternate indication and/or population to that in the proposed study, and there is intent to obtain approval for the new indication or to update the local product labeling with the results of the study (e.g. Phase 3b or pediatric studies).
This restriction does not apply to studies involving healthy volunteers. Studies in healthy volunteers (those where study participants do not receive any medical treatment as part of the study) may be placed in any country that has the appropriate medical and research infrastructure to conduct the clinical study.
3.7 Study Team Responsibilities
Pfizer-sponsored clinical research must be designed, conducted, and monitored to ensure the protection of the rights and safety of study participants and the integrity of the research data, in compliance with Pfizer standards, applicable laws, regulations, and ethical standards. Pfizer may outsource the conduct of all or part of an interventional clinical study to a CRO, but the sponsor responsibilities for the quality and integrity of study conduct and data reside with Pfizer.
When Pfizer contracts with a CRO, the study team must comply with the requirements for requesting, contracting and managing a CRO in accordance with the principles set forth in OS01-GSOP Requesting, Selecting, Contracting and Managing Vendors SOP
When Pfizer collaborates with another sponsor on the joint development of a product, with a third-party, or a CRO to conduct a study, Pfizer and the other Sponsor, third-party, or CRO must agree, in writing, which party has responsibility for each process of the clinical study, including the Good Manufacturing Practice (GMP), GCP, and PV responsibilities.
Pfizer-sponsored interventional clinical studies must be monitored by trained, qualified and experienced personnel to assess the protection of study participants' rights and welfare. The monitors also need to ensure that the study is being conducted in accordance with ICH-GCP, local regulations, the protocol and in accordance with the principles set forth in CT08 – Clinical Site Management and Monitoring SOP and CT33 – Study Training SOP. In addition, a study monitoring plan must be created and maintained for each study.
All suspected significant deviations from ICH-GCP, other applicable Good Practices, applicable regulatory requirements, and legal and ethical standards must be promptly reported to Pfizer and regulatory agencies, as appropriate. Investigation and appropriate action must be taken to ensure study participant safety and data integrity, a return to compliance, and corrective and preventative actions, in accordance with the principles set forth in QMS01-GSOP Management of Qualifying Quality Issues SOP.
3.9 Data Monitoring Committees
Data Monitoring Committees (DMCs) are used to monitor safety in randomized studies with mortality or major morbidity as primary or secondary endpoints, studies where study participants may be at elevated risk of such outcomes, and other studies where an independent review of study data is warranted. Establishment and conduct of DMCs must follow international and local requirements, in accordance with the principles set forth in CT22 – Use of Data Monitoring Committees and Conduct of Interim Analysis SOP.
3.10 Control of Investigational Product
All investigational products are tracked and controlled from the time they leave Pfizer through to their use, appropriate disposal or return to Pfizer. Pfizer ensures that records documenting the control of investigational product are established for all Pfizer-sponsored interventional clinical studies, in accordance with the principles set forth in CT13-GSOP Investigational Product SOP.
3.11 Organ Transplantation
Pfizer supports the ethical principles articulated by the World Health Organization's Guiding Principles for Human Cell, Tissue and Organ Transplantation . Additionally, all investigators for Pfizer-sponsored interventional clinical studies involving study participants who have received or who will receive an organ transplant related to participation in a study are expected to follow the same ethical principles.
3.12 Essential Documents
All essential documents for Pfizer-sponsored interventional clinical studies must be maintained and archived in accordance with ICH GCP standards, applicable regulatory requirements, and in accordance with the principles set forth in CT01-GSOP – Trial Master File SOP.
3.13 Post Study Care
The protocol must clearly define the appropriateness, relevance, and feasibility of providing investigational product and/or alternative therapies to study participants at the conclusion of the study, or other necessary follow-up care (e.g., unresolved adverse events). This determination may include consideration of local availability of the treatment and alternative treatments, the development stage of the investigational product, the seriousness of the disease being treated, the global results of the research program, the overall safety and risk/benefit ratio of the investigational product, as well as individual study participant's results.
3.14 Study Participant Access to Health Infomation from Studies
Study participants may request access or corrections to health information arising from their participation in a Pfizer-sponsored interventional clinical study. Such requests are made to the physician or investigator treating them in the study. Investigators who request access to laboratory or other data about study participants must submit such requests to the study manager. Pfizer study teams must work with Research & Development (R&D) Legal and the Global Privacy Office to determine the appropriate response to such requests, taking into account local regulations and standards.
The privacy of study participants and the confidentiality of their personal information must be protected in accordance with REG09 Global Medical, Regulatory, and Research and Development Policy on Protecting the Privacy of Personal Information SOP.
3.15 Managing Potential Investigator Conflicts of Interest
Pfizer manages potential investigator conflicts of interest and bias by: 1) designing clinical trial protocols that utilize sound study design, including, when appropriate, randomization and blinding; 2) conducting source document verification at investigator sites as described in the study monitoring plan; 3) following a rigorous investigator selection process; 4) maintaining compliance with regulatory disclosure of payments to investigators; 5) publically disclosing payments to healthcare professionals, including investigators; and 6) adhering to a process for establishing fair-market-value for services of healthcare providers, including investigators, in accordance with WRD Policy 201, Anti Corruption, GPIHP and External Funding.
4. Required Forms and Templates