A. Organizational Structure

The organization or individual conducting the research shall be fully responsible for the operation and performance of the research. The organization shall be a legal entity with a governing body that sets policy and that is fully responsible for the adminstrative aspects of the organization and its related research activities.

The relationship, roles and responsibilities of the organizations and/or individuals sponsoring or conducting the study should be carefully defind in writing.

For example, this should include delinating the roles and responsibilites to be assumed by the study sponsor and the contractor(s) in communicating various aspects of the study as well as data ownership, archiving etc.

B. Personnel

Personnel engaged in epidemiologic research and related activities shall have the education, training and/or experience necessary to competently perform the assigned functions. The organization shall maintain a current summary of training and experience of these personnel. A job description for each individual engaged in or supervising activities shall be maintained and updated periodically.

II. Facilities, Resource Commitment, and Contractors

A. Facilities

Adequate physical facilities shall be provided to all those engaged in epidemiologic research and related activities. Sufficient resources, eg., office space, relevant equipment, and office/professional supplies, shall be available to ensure timely completion of all studies. Suitable storage facilities shall be available to maintain research materials in a safe and secure environment.

B. Resource Commitment

Sufficient commitment shall be made at the beginning of each study to ensure its timely and proper completion (see section III-K protocol).

C. Contractors

For the purposes of ensuring and documenting the contractor`s conformance with the guidelines of Good Epidemiology Practices, it is recommended that the study sponsor have the right during the course of the study, and for a reasonable period following completiong of the study, to inspect the contractor`s facilities, including equipment, technical records, and records relating to the work conducted under the sponsor`s contract.

III. Protocol

Each study shall have a written protocol. This protocol must be approved before study begins (see section IV: Review and Approval).

The protocol should include the following:

1. A Descriptive title.
2. The names, titles, degrees, addresses, and affiliations of the study director, principal investigator, and all co-investigators.
3. The name(s) and address(es) of the sponsor(s).
4. An abstract of the protocol.
5. The proposed study tasks and milestones, including study approval data (data protocol signed by all signatories), study start date (first date that the protocol is implemented), periodic progress review dates, and completion date.
6. A statement of research objectives, specific aims, and rationale:
   The statement should identify the immediate purpose of the investigation. For example, it might also indicate whether the study will be exploratory data analysis, hypothesis testing, or a combination of both as well as whether the proposed study will address previously unanswered questions, will attempt to corroborate or confirm previous findings, or will be routine epidemiologic surveillance.
7. A critical review of the relevant literature to evaluate applicable findings.
   For example, the literature review should encompass animal and human experiments, clinical studies, vital statistics, and previous epidemiologic studies. The literature review should be of sufficient depth to identify potential cofounders and effect modifiers and to determine areas where new knowledge is needed.
8. A description of the research methods, including:
   1. The overall research design and strategy and reasons for choosing the proposed study design.
   For example, case control, cohort, cross-sectional, nested case control or other hybrid designs.
   2. The data sources for exposure, health status, and risk factors.
   For example, questionnaries, biological measurements, exposure/work history record reviews, or exposure/disease registries.
   3. Clear definitions of health outcomes, exposure, and other measured risk factors as well as selection criteria, as appropriate, for exposed and nonexposed persons, morbidity or mortality cases, and referent groups.
   4. Projected study size, and if appropriate, statistical power.
   5. The methods to be used in assembling the study data.
   This should include a description of, or reference to, methods used to control, measure, or reduce various forms of error - eg, bias due to selection, misclassification, interviewer, or confounding - and its impact on the study. Pretesting procedures for research instruments and any manuals and formal training to be provided to interviewers, abstractors, coders, or data entry personnel should be described or referenced.
   6. Procedures for handling the data in the analysis.
   This should include a description of procedures for defining or categorizing exposure and health outcome variables for purposes of analysis. It should also include provisions for assessing dose-response relationships and treatment of potentially confounding and effect modifying variables.
   7. Methods for data analysis.
   This should include procedures to control, if possible, sources of bias and their influence on results and a description of planned comparisons and methods for analyzing and presenting results.
   8. Major limitations of the study design, data sources, and analytic methods.
   9. Criteria for interpreting the results.
   This should include a brief discussion of the characteristics of the proposed study design, including limitations, that will influence the discussion of the results. It also should state criteria for assessing biological plausibility, internal and external consistency of the findings, and casual inference. The statistical tests to be applied to the data and procedures for obtaining point estimates and condience intervals of measures of occurence or association should also be described.
9. A description of plan for protecting human subjects.
   This should include information about whether study subjects will be placed at risk as a result of the study, under what circumstances informed consent will be required, and provisions for maintaing confidentiality of information on study subjects. (See section IV: Review and Approval; section V: Study Conduct; section VI: Communication; and section VII: Archiving)
10. A description of, or reference to, quality assurance and quality control procedures for all phases of the study. As appropriate, include certification and/or qualifications of any supporting laboratory or research groups (see section VIII: Quality Assurance).
11. A description of plans for disseminating and communicating study results (see section VI: Communication).
12. Resources required to conduct the study.
    Describe, for example, time, personnel, and equipment required to conduct the study, including a brief description of the role of each of the personnel assigned to the research project.
13. The bibliographic references.
14. Addenda, as appropriate.
    For example, correspondence, collaborative agreements, institutional approvals, and samples of the informed consent forms, questionnaries, and representative sampes of other documents to be used in the study.
15. A dated protocol review and approval sign-off sheet for the study director, principal investigator, co-investigators, and all reviewers (see section IV: Review and Approval).
16. Dated amendments to the protocol.

IV. Review and Approval

Review of study protocols and final reports should encompass all aspects of a study outlined in the guidelines for Good Epidemiology Practices (see section III: Protocol and section V-D: Study Conduct). All reviews shoud be conducted in a timely fashion. It may be appropriate to involve worker or community representatives in the planning and review of the protocol and study results.

A. Scientific Review

The study protocol shall receive appropriate scientific review by qualified person(s) who are not part of the investigative team to ensure that the study is designed to address that objectives of the research and that the protocol is written according to Guidelines for Good Epidemiology Practices. The nature and circumstances of this review shall be documented (see section III: Protocol).

The scientific aspects of the completed study shall receive appropriate technical review to ensure that the abstract, summary and conclusions are supported by the underlying data, methods, and analysis (see section V: Study Conduct).

B. Ethical Review

The ethical aspects of each study protocol shall be reviewed by an institutional review board or other comparable review procedure.

This review should consider:

1. Obligations to research subjects.
   For example, protecting the welfare of study subjects; the need for, and content or, communications and informed consent;  protecting privacy; and maintaining confidentiality.
2. Obligations to society.
   For example, avoiding conflicts of interest; avoiding partiality; disseminating the study`s findings; data sharing; and pursuing responsibilities with due diligence.
3. Obligations to funders and employers.
   For example, specifying obligations in contractual form of how research is to be conducted and how it may involve ethical, technical, adminstrative, or legal responsibilities; presenting methods and alternatives; and protecting privileged information.
4. Obligations to colleagures.
   For example, promoting and preserving public confidence in epidemiologic research while not over or underestimating the methods or results or epidemiologic inquiry; reporting methods and results; and disseminating the study`s findings.

C. Administrative Review

The adminstrative aspects of the study protocol shall receive appropriate review and written approval by sponsors, contractors, and associated third parties to ensure that sufficient resources are available to complete the study in a timely and proper fashion.

Reports shall include a statement that the study was completed in accordance with the protocol, including any approved modifications to the protocol, and in accordance with the GEPs. Any deviations from the GEPs shall be explained and documented (see section VIII: Quality Assurance).

V. Study Conduct

While the study director shall be responsible for the overall research program, the principal investigator shall be responsible for the individual research project, including the day-to-day conduct of the study, interpretation of the study data, and preparation of a final report. These responsibilities extend to all aspects of the study including periodic reporting of study progress as well as quality assurance. In some situations, the study director and the principal investigator may be the same person.

To ensure the proper conduct of the study, personnel shall adhere to sound research principles and practices established according to the protocol.

A protocol must be approved before the study begins. The study shall be conducted in accordance with the protocol; all deviations from the protocol shall be properly documented and authorized by the principal investigator.

If a decision is made not to complete a research project, the reasons for that decision shall be put in writing, dated, and signed by the responsible party, ie, the individual who makes the decision to terminate the study.

A. Protection of Human Subjects

Procedures for protecting human subjects shall be followed (see section III-I: Protocol and section IV-B: Review and Approval). Confidential information about study subjects shall be protected using established procedures.

If stipulated by the study protocol and/or required by an institutional review board, each study subject shall be informed about the purpose of the study and any risks associated with participating in the study. Written consent, if required, shall be obtained from each study subject before he/she participate in the study.

Written consent shall include at a minimum:

1. Purpose of the research or study.
2. Name(s), address(es), and phone number(s) of personnel available to answer questions about the research and the rights of study subjects.
3. Expected duration of subject`s participation.
4. Eligibility requirements for study participation.
5. Possible benefits to the study subject or other of study results.
6. Statement on the voluntary nature of participation in the study and the right of the study subject to discontinue participation at any time.
7. Statement of confidentiality of records identifying the study subject, including reasonable exceptions to absolute confidentiality, eg, sharing of information with the study subject`s personal physician or as required by court order.
8. Description of any foreseeable risks or discomforts to the study subject.
9. Statement of availability of results.

B. Data Collection and Verification

All data collected for the study should be recorded directly, accurately, promptly, and legibly. The individual(s) responsible for the integrity of the data, computerized and hard copy, shall be identified.

All procedures used to verify and promot the quality and integrity of the data shall be outlined in writing (see section VIII: Quality Assurance). An historical file of these procedures shall be maintained, including all revisions and the dates of such revisions. Any changes in the data enteries shall be documented.

C. Analysis

All data management and statistical analysis programs and packages used in the analysis should be documented. All dated versions used in research shall be kept with accompanying documentation (see section VII: Archiving).

D. Study Report

Completed studies shall be summarized in a final report that accurately and completely presents the study objectives, methods, results and the principal investigator`s interpretation of the findings.

The final report shall include at a minimum:

1. A descriptive title.
2. An abstract.
3. Purpose (objectives) of the research as stated in the protocol.
4. The names, titles, degrees, addresses and affiliations of the study director, principal investigator, and all co-investigators.
5. Name(s) and address(es) of sponsor(s).
6. Dates on which the study was initiated and completed.
7. Introduction with background, purposed, and specific aims of the study.
8. A description of the research methods, including:
   a. the selection of study subjects and controls.
   b. the data collection methods used.
   c. the transformations, calculations, or operations of the data, and
   d. statistical methods used in data analyses.
9. A description of circumstances that may have affected the quality or integrity of the data (see section VIII: Quality Assurance).
10. A summar and analyses of the data.
    Include sufficient tables, graphs, and illustrations to present the pertinent data and to reflect the analyses performed.
11. A statement of the conclusions drawn from the analyses of the data.
12. A discussion of the implication of study results.
    Cite prior research in support of an in contrast to present findings. Discuss possible biases and limitations in present research.
13. References.
14. A statement describing the location where all source data and the final report stored (see section VIII: Archiving).
15. A dated study review sign-ff sheet for the study director, principal investigator, co-investigators, and reviewers and/or auditors (see section IV: Review and Approval and section VIII: Quality Assurance).

VI. Communcation

Each organization shall predetermine procedures under which communications of the intent, conduct, results, and interpretations of an epidemiologic study will occur, including what function individuals associated with the research must fulfill. These individuals should include the principal investigator, study director, and/or the sponsor. This procedure may be documented in the form of a company standard operating procedure, in the study protocol, or through contractual agreement.

Government agencies shall be informed of study results in a manner that complies with applicable regulatory requirements.

Scientific peers shall be informed of study results by publication in the scientific literature or presentations at scientific conferences, workshops, or symposia, to the extent possible.

All study subjects shall be informed of the study results and any interpretation of the study findings and conclusions, to the extent possible. Study subjects may be informed in person, through meetings, video tapes, letters, newsletters, summary reports, or other appropriate communcation. Information about study results shall be provided in language appropriate for the audience.

VII. Archiving

There shall be physically secure archives for the orderly storage and expedient retrieval of all study related material. An index shall be prepared to identify the archived contents, to identify their location, and to identify by name and location any material that by their general nature or not retained in the study archive.

Access to the archives shall be controlled and limited to authorized personnel only. Special procedures may be necessary to ensure that access to confidential information is limited and that the confidentiality of information about study subjects is protected (see section III-I: Protocol).

At a minimum the study archive should contain, or refer to, the following:

1. Study protocol and copies of all approved modifications.
2. A final report of the study.
3. All source data and, where feasible, specimens. A printed sample of the master computer data file(s) with reference to the location of the machine readable.
4. Documentation adequate to identify and locate all computer programs and statistical procedures used, including version numbers where appropriate (see section V-C: Study Conduct).
5. Copies of computer printouts, including relevant execution code, that form the basis of any tables, graphs, discussions, or interpretations in the final report. Any manually developed calculations shall be documented on a work sheet and similarly retained.
6. Correspondence pertaining to the study, standard operating procedures, informed consent releases, copies of all relevant representative material, copies of signed institutional review board and other external reviewer reports, and copies of all quality assurance reports and audits.
   Include, for example, questionnaires, name, make and model numbers of relevant measurement instruments, calibration information and procedures.
7. Original documents for the following research materials shall be included in the archives.
   1. Laboratory / research notebooks.
   2. Coder modification notebooks.
   3. Signed and dated copies of the research protocol and final report.

VIII. Quality Assurance

Written procedures shall be established to ensure the quality of the data used in a study (see section III-J: Protocol and section V: Study Conduct). These procedures shall addres data collection and completeness, coding and computer input, storage, and retrieval, and data validation and analysis. Any deviations from the GEPs shall be explained and documented in the final report (see section IV-C: Review and Approval).

An individual who is not part of the investigative team should be assigned as a study quality assurance auditor. This individual shall, no less than annually, review study compliance with the written quality assurance procedures. The study quality assurance auditor shall prepare a written summary of the audit. The principal investigator should respond in writing to the audit report, including any remedial actions taken.

Quality assurance activities shall address the preceeding sections of these guidelines as well as monitor conformance with established standard operating procedures (SOPs) (see Appendix 1: Standing Operating Procedures).

APPENDICES

Standard Operating procedures

The Guidelines for Good Epidemiology Practices address the conduct of epidemiologic studies rather than the management of epidemiologic research programs. Many of the suggested guideline requirements can be fulfilled by reference to standard operating procedures for the research program.

Standard operating procedures (SOPs) are written, detailed descriptions of routine procedures involved in performing epidemiologic studies. Reproducibility, accuracy, and validity are ensured when SOPs are designed to clearly reflect each facility`s research procedures. It should be the responsibility of a designated individual to develop and continuously review and update SOPs pertaining to his area of responsibility. Signatures of approval from the department`s managing personnel or appropriate designees should be obtained for all new and updated versions. Significant changes in established SOPs should be maintained, including all revisions and dates of such revisions. The manual of SOPs should be readily available to all research and administrative personnel.

1. A statement of the purpose of the standard operating procedure.
2. A detailed description of the procedure.
3. The person responsible or the training level required to perform the procedure.
4. The date of issue (effective date).
5. The issue number / revision number.
6. Sigature or preparer.
7. Authorizing / reviewing signature of management.

Examples of research program activities for which SOPs could be established include:

1. Procedures for collecting raw data.
2. Procedures for validating the completeness of the study population.
3. Procedures for coding death certificates.
4. Procedures for assessing error rates in data abstraction and coding.
5. Security procedures for ensuring the integrity of the raw data and computer records.
6. Procedures for archive management.
7. Procedurs for standard industrial hygiene sampling and analytic methods.
8. Procedures for scientific review.
9. Required composition of scientific review boards.
10. Procedures for data analysis.
11. Procedures for communications.

Appendix 2

Glossary of Terms used in this text