Starting a Research Project at SKMCH&RC

1.1 What is Clinical Research?

For the purposes of these guidelines, clinical research is defined as a systematic activity that involves one or more of the following:

• People (typically patients, their careers, staff or volunteers)
• Their tissue
• Their organs
• Their personal information

And that meets all three of these criteria

• Attempts to answer a clearly defined question
• Employs systematic and rigorous methods
• Leads to new knowledge that may be transferable/generalizable

The first two criteria will also be met by audit and service evaluation activities, but these differ from research in that audit seeks to measure existing practice against evidence-based standards, and service evaluation addresses local service issues.

You need to register your project if it involves participants for whom SKMCH&RC has a duty of care, i.e. patients, their carers or staff including data, images or tissue derived from the participants. You will also need to register your research if it occurs in SKMCH&RC premises even if it does not directly involve patients as would be the case of a medical physicist working on the development of instrumentation. You may begin your project only after you have received a formal letter of approval, following research review applicable to your research project

Some examples:

• If participants are recruited by virtue of their relationship with SKMCH&RC, but the study involves interviewing subjects in their own homes, the hospital has a duty of care.
• If the participants are recruited by virtue of their membership of a community group, and are interviewed on SKMCH&RC premises, SKMCH&RC has a duty of care.
• If the participants are recruited by virtue of their membership of a community group, and are interviewed in their homes, SKMCH&RC does not have a duty of care. In this case, if the subjects were recruited or identified because of lists/data available at SKMCH&RC, the research still falls under the purview of SKMCH&RC

1.2 Types of Research Projects Undertaken at SKMCH&RC:

All clinical departments at the hospital are involved in investigator-initiated studies and clinical trials. Following three sections housed in Abdul Hafiz Research Wing are dedicated to perform and facilitate research in variety of ways:

• Clinical Research Office
• Basis Science Research Lab
• Cancer Registry and Clinical Data Management

Pharmacy, nursing, radiology, pathology, ancillary teams and other relevant services also provide support for various research studies where required. Human subject research activities in diverse areas related primarily to the diagnosis and treatment of cancer are undertaken at the hospital. We are currently not involved in animal research activities.

Table 1 below gives an overview of the various types of research projects undertaken at the hospital and their approval requirements;

Table 1: Types of Research Projects Undertaken at SKMCH&RC

* Scientific review in case of international multicenter investigational new drug /device/biologics trials is done during the internal feasibility assessment process facilitated by the Clinical Research Office. Proposed investigators, who are subject area experts, are part of this assessment and studies are reviewed for both scientific content and their logistic feasibility at the hospital.

Research studies to be done in collaboration with other organizations would require additional steps which may involve IRB review at collaborating institute, collaboration data/material transfer and funding agreements, and other applicable regulatory requirements as per national and international laws and regulations. No collaborative research can be undertaken without the involvement of a designated member of SKMCH&RC staff as the institutional facilitator for that project. (See section 6 for details.)

1.3  Conducting Research at SKMCH&RC

• Registration of research – Registration of research is done by submission of the research studies  to the clinical research office. Complete guidance on how to make a submission of research study is provided in the Appendix I Clinical research office shall facilitate scientific and ethical review of studies as applicable.
• Scientific review – The MD will nominate a scientific review committee for projects that qualify for scientific review. SRC is constituted wilth MD, Secretary SRC, Secretary IRB, at least two members from the consultant staff and at least one representative from the basic science research group and the cancer registry and clinical data management (CRCDM) section . The committee will advise and facilitate the investigators and may support, oppose or suggest modifications to the proposal.
• IRB approval – Once scientific approval is obtained, the study should be submitted for approval by the IRB. Clinical research office staff will guide and facilitate the principal investigator in this process. The primary objective of obtaining IRB approval is to ensure the protection of the rights, safety and well-being of study participants and to address ethical issues. The IRB may approve, reject, modify or defer pending further information. Research projects which fall in the following categories also need to be submitted to the Research Ethics Committee (REC) of the National Bioethics Committee (NBC), Pakistan for review and approval before these are initiated
• All research (medical or social science) projects involving human subjects, whether as individuals or communities, including surveys, drug/device trial, the use of fetal material, embryos and tissues from alive or the recently dead done with one or more of the following
  • International funding specifically given for research done anywhere in Pakistan e.g. Research Advocacy Fund (RAF), DFID, USAID etc
  • Funded or supported by the Government of Pakistan
  • Any other research either done all over Pakistan or is a multi-province
  • Drug trials for registration

Click here to download NBC application form, exemption request form and guidance sheet (used with thanks and permission of National Bioethics Committee, Pakistan http://nbcpakistan.org.pk/downloads.html

• Human subject research involving no more than minimal risk qualifies for exemption from full quorum IRB review. These studies will not require approval by SRC as the scientific and ethical review is completed jointly by designated IRB members. Appendix I contains detailed guidance on which type of projects may qualify for IRB exemptions.
• Application for SKMCH&RC funds (if applicable)
• Maintenance of a site file and research records – This includes essential documentation related to the study such as protocol, signed consent forms, case report forms/source data , ethics review approval and related communication record, regulatory approval (where applicable), medication management records (in case of studies involving investigational new drug/device/biologic interventions), hazardous material management and maintenance of equipment used in research (if applicable). Investigators should retain a record of study team qualification and delegation of study related duties as per their qualification and experience. In addition , a record of research oversight by the principal investigator or training supervisor as applicable should be maintained . For interventional drug/device /biologic studies, reporting of adverse events as per hospital adverse event reporting (ADR) system should be ensured along with the sponsor and IRB reporting requirements. In addition, all incidents , sentinel events and near misses in a research participant should be reported as per  the hospital quality improvement (QI) and sentinel event reporting system. Clinical research shall educate researchers on responsible conduct of research and research-related documentation requirements for all prospective research studies via series of research oversight meetings (for details see section on investigator’s responsibilities on responsible conduct of research)
•  Preparation of periodic progress reports – IRB at SKMCH&RC collects periodic progress reports for all IRB approved studies reviewed by the full quorum committee as per frequency defined by the IRB (at least annual frequency). In addition, investigators are required to submit all amendments to the protocol for IRB review and approval as well as a final report at study completion. Investigators are also required to notify the IRB in case of changes in the study team.
• Research Compliance and Integrity Oversight: As part of hospital’s commitment to facilitate researchers in ensuring responsible research conduct, a representative from the clinical research office team meets investigators of all prospective studies, periodically, during the course of the study to provide guidance on appropriate record keeping for research and to enhance awareness of researchers about responsible research conduct. At study close out, all study records are collected at clinical research office for central archiving and retained as per hospital record retention and archival policy.

1.4 Submission Requirements

For details related to submission Requirements, kindly see appendix I.

The following general format should be used as guidance for submitting a synopsis and related documents (such as Informed consent forms etc.) for review and approval;

I. Study Title
II. Investigator(s) With Institutional Affiliations
III. Introduction
IV. Objectives
V. Definitions
VI. Hypothesis
VI. Materials And Methods

Study Design: Describe in detail the design and methodology of the study. Identify and distinguish between those procedures that are standard of care and those that are experimental. Provide a detailed description of the planned data collection, specific outcomes, and criteria for evaluation and endpoint definition.

Setting

Duration: Include the frequency and duration of each activity and the total length of subject participation.

Sample Size and Sampling Techniques: If applicable; include information on stratification or randomization plans, the maximum number of subjects you plan to recruit for this study. If this is a multi-site study, indicate the projected total subject accrual.

Inclusion and Exclusion Criteria

Study Procedures:  Include details on medical procedures

Data Analysis and Statistical Methods: Describe the statistical considerations for the study, how the sample size was determined, and how the results will be analyzed, if applicable.

For Interviews/Focus groups:   Attach copies of any scripts and/or questions that will be used to guide the interviews/groups. Indicate the member(s) of the study team who will conduct the interviews/focus groups and any necessary qualifications such as special training, supervision etc.

For Studies Involving Surveys/Questionnaires:   List all of the measures/instruments that will be used for this study and attach copies for these. Indicate the member(s) of the study team who will use these measures/instruments and any necessary qualifications such as special training or licenses.

For Studies Involving Use of Existing Data/Specimens: When using existing data/specimen and Applying for Exemption, Describe the following: the source of data/specimen and the process used to unlink the data or specimen/make it anonymized/ (the process by which identified data is recorded in a way that individuals cannot be identified)

VIII. HUMAN RESEARCH SUBJECT PROTECTION

Risks, Discomforts and Potential Harms: Describe the risks associated with each research intervention (physical, psychological, social, and other factors) with the estimated probability that given harm may occur and the potential reversibility. Describe the safety precautions that will be taken to minimize risks/harms. When appropriate, include a study monitoring plan for the safety of participants and for the validity and integrity of data.

Potential Benefits and Alternatives:

Describe any potential for direct benefits to participants in the study. There may be no direct benefits.  Also, include information on the importance of the knowledge that may reasonably be expected to result.  Also describe the alternatives available to patients in cases of non-participation in research.

Informed Consent: Indicate the types of consent that will be involved in this study and attach copies of the informed consent/assent document that will be used for this study. If a waiver of Informed consent is considered justified, describe with reasoning.

Data Privacy and Confidentiality: How will the data for this study be collected and recorded? Describe the provisions to protect the privacy of the individual.  Where will the research data be stored & how it will be secured? Who will have access to the study records or data? Specify their name, role and affiliation.

IX. RESOURCE REQUIREMENT
Monetary, logistic and administrative or other

X. REFERENCES