Health research in the heart of Vancouver

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Navigating the Clinical Research Process: From ideation to completion

You have a great research idea…now what?

It is important to plan all aspects of your clinical research study as early as possible, and prior to beginning your project, to prevent challenges in data collection, human resources, budgets, regulatory compliance, or timelines. Dedicate significant time to designing your study: clearly articulate your objectives, hypothesis, and how you will meet these objectives. If necessary, be sure to obtain professional advice on protocol design, data collection, and analyses. CHÉOS provides support for clinical researchers in the form of:

  • Project and data management
  • Methodology and statistics
  • Program evaluation
  • Regulatory affairs
  • Trial monitoring, and
  • Health economics

CHÉOS also provides a one-hour free consultation. We recommend that you conduct a literature review and prepare specific questions prior to your consultation to ensure that you get the most out  of your consultation. To help you prepare, our staff have prepared questions that they routinely ask during the consultation process. View this document here.

This process map is designed for Investigators conducting their own clinical research study, and acting as “sponsor-investigator”. However you may access this process map at any point, depending on the applicability to your research.

Researchers looking to obtain access to Cerner should click here.

PROJECT DEVELOPMENT

LITERATURE REVIEW

A proper literature search is integral to defining your research question and designing your study. Here are a few examples of available resources that can help in conducting an in-depth review:

REFINE IDEA

If your research question is too broad, you will have difficulty designing a focused study and collecting data to answer your hypothesis. If it’s too narrow, you will have difficulty finding the appropriate participants. Engaging patients in research is a relatively new aspect of clinical research, but has recently shown to improve participant experience and outcomes in clinical trials.*

The B.C. SUPPORT (Support for People and Patient-Oriented Research and Trials) Unit is a “multi-partner organization created to support, streamline, and increase patient-oriented research throughout B.C. Patient-oriented research is research that engages patients as partners and focuses on patient-identified priorities with the goals of improving patient experiences, health outcomes, and the health system”. The B.C. Unit is one of ten SUPPORT Units established across the country by the Canadian Institutes of Health Research (CIHR) as part of Canada’s Strategy for Patient-Oriented Research (SPOR).

Four CHÉOS Scientists currently serve as Methods Cluster Leads. Under the Methods Cluster structure, experts in specific methodological approaches to patient-oriented research are connected to foster innovation and collaboration.

See the B.C. SUPPORT Unit website for more information about the Unit and the services they provide to researchers to help develop patient engagement plans.

*Baker, RG (2014). Evidence boost: a review of research highlighting how patient engagement contributes to improved care. Ottawa, ON: Canadian Foundation for Health Improvement

CREATE A PROPOSAL

If you need to create a proposal to apply for funding, and the funding agency does not have their own template, you can use the CHÉOS template here.

Planning Methodology

  • Need help understanding the basics of statistics? See here.
  • The Patient-Centered Outcomes Research Institute (PCORI) recently released a detailed report on methodology standards, beginning with formulating research questions through to data analyses. See the PCORI document here.
  • Contact a Biostatistician

Preparing a Budget

  • CHÉOS provides a detailed listing of possible set-up costs, procedures, and incidental costs. Don’t forget that funding can be subject to overhead (indirect) costs of up to 40% (pharmaceutical or device company-funded studies). UBC provides a table of rates for indirect costs. You must have a UBC Campus Wide Login (CWL) to access this table. Instructions for obtaining a CWL are located here.
    • For a list of potential expenses, see here.
    • Download a site-level study budget template here.
  • Providence Health Care (PHC) does not have a list of fees for common research procedures or tests associated with research projects (e.g. lab tests), but attached is a list of the departmental contacts, who may be able to help you with your budget.
APPLY FOR FUNDING

CIHR is the primary source of federal funds for health research in Canada; other suggestions for funding are:

  • Disease-related foundations (e.g. Heart and Stroke Foundation, Cystic Fibrosis Foundation).
  • Industry partners. A pharmaceutical or medical device company may not provide direct funding for a project, but they may consider donating the study intervention (e.g. drug or device).
  • St. Paul’s Hospital Foundation.
  • The Providence Health Care Research Institute (PHCRI) website lists some awards and funding opportunities.
  • PHCRI and CHÉOS have weekly or bi-weekly e-newsletters that include funding opportunities. Subscribe at:
    • PHCRI
    • CHÉOS — Scroll to the bottom of the page and enter your email address. 

For UBC Researchers

The UBC Office of Research Services (ORS) also maintains a list of upcoming funding opportunities for UBC researchers.

SPARC (Support Programs to Advance Research Capacity) offers services and resources to UBC faculty members to make the most of their funding proposals. They will also provide examples of sample grant proposals.

Funding agencies usually require departmental approval for your proposal. This includes your department head and the ORS at UBC. UBC provides an excellent graphic of the steps required and the timelines for developing and submitting a proposal for funding.

For further information on signature requirements and timelines, see here.

Once you have received your funding, contact PHC Finance for information on setting up a study account. Depending on the source of your funding, some accounts are set up under UBC, and some under PHCRI.

TURN YOUR PROPOSAL INTO A PROTOCOL

While you can use your proposal as a template for your protocol, a proposal is written to only obtain support for your study. A study protocol contains detailed instructions on how the study will be conducted, and includes information to meet regulatory requirements (if applicable). CHÉOS provides protocol templates for use in interventional and non-interventional clinical studies.

  • The National Institutes of Health (NIH) in the US, recently released a protocol template for Phase 2 and 3 clinical trials funded by the NIH that are being conducted under a Food and Drug Administration (FDA) Investigational New Drug (IND) or Investigational Device Exemption (IDE) Application. View the NIH document here.
  • Statistics and Statistical Analysis Plan: What is the purpose of the analysis and how will the results be used? (See CHÉOS consultation document in the introductory section.)
  • Note that UBC requires that any protocol that is more than minimal risk*, must undergo a peer review. See UBC Research Ethics, General Guidance Notes, Article 8.2 for more information. Peer review should come from a colleague not involved in the research, or a supervisor or mentor for trainees. In rare circumstances, it may come from the funding agency or sponsor.

*The BC Ethics Harmonization Initiative (2013) defines minimal risk research as “research in which the probability and magnitude of possible harms implied by participation is not greater than those encountered in the aspects of everyday life that relate to the research”. Read the minimal risk common criteria guidelines here.

PROJECT SET-UP

Depending on the complexity of your study and assuming reasonable turnaround times, an estimated timeline for project set-up is from 4 to 9 months.

IS YOUR PROJECT A RESEARCH STUDY OR QUALITY IMPROVEMENT/PROGRAM EVALUATION?

According to the Tri-Council Policy Statement (Ethical Conduct for Research Involving Humans) TCPS 2 (article 2.1) any research which involves human participants or live biological material which is executed through a disciplined inquiry or systematic investigation, requires a Research Ethics Board (REB) review.

Quality Improvement
There can be significant overlap between Quality Improvement (QI) and research. Generally, QI is conducted to improve or measure the effectiveness of a program or service; research is a more structured investigation designed to contribute to generalizable knowledge.

Policy or legislative requirements stipulate that research projects involving people or their health information must be reviewed by a REB. This raises a number of questions. For example:

  • What should be done with projects that are not considered research but involve people or their health information?
  • Should quality improvement or program evaluation projects also be assessed for their risk to people?
  • What are the characteristics of research versus quality improvement/ program evaluation projects? How do you decide what to review?
  • How should ethics oversight of these “non-research” projects be approached?

There is significant debate over these questions. The ARECCI (A pRoject Ethics Community Consensus Initiative) tool, developed by Alberta Innovates – Health Solutions (AIHS) can be used to assist in determining if your project is a research study or a quality improvement/program evaluation project.

ARECCI tool (if required) 
Even if your ARECCI tool results indicate your project is quality improvement or project evaluation, you may wish to have it assessed by the Research Ethics team who can then provide documentation that the project does not need ethics review. Contact Julie Hadden (Manager, Ethical Reviews) if you need this documentation.

QUALITY ASSURANCE/IMPROVEMENT PROJECT

In 2017, a physician-led QI initiative opened to VCH and PHC physicians who are interested in learning about and doing QI work. They will receive support for their work on a project as well as education and access to our physician led QI team. See the QI document here.

CLINICAL RESEARCH

NOTE: If you have questions pertaining to behavioural research projects, please contact PHCRI.

Health Canada Clinical Trial Applications (CTAs), ethics submission, contract review, and administrative approvals can often be undertaken simultaneously. Check with your local institution’s research administration for more information.

The following links are provided to assist in obtaining the approvals needed to start your research project at Providence Health Care. Your project must be reviewed by the PHC REB to ensure participant protection, privacy and confidentiality standards are met. You must also obtain organizational approval to conduct your research study. This is completed through the REB as well.

OBTAINING HEALTH CANADA APPROVAL

If your study is testing a new drug, or an approved drug outside of its approved use, then you will have to submit a Clinical Trial Application (CTA) with Health Canada. CHÉOS has a regulatory affairs department that can submit a CTA, manage the lifecycle of your regulatory application and liaise with Health Canada on your behalf. Note that you must have your No Objection Letter (NOL) for drug studies before the REB will provide their final approval.

If your study involves an investigational medical device, you may need to obtain an Investigational Testing Authorization (ITA) from Health Canada. Contact Dana Nohynek for further advice.

In August 2019, Health Canada, Regulatory Operations and Enforcement Branch (ROEB), released the long-awaited Guidance Document (GUI-0100), created to provide guidance in interpreting the regulations around conducting a regulated clinical trial in Canada.

“This guidance document will help anyone who is involved in the conduct of clinical trials of drugs in human subjects in Canada to comply with Part C, Division 5 of the Food and Drug Regulations and to understand the International Council for Harmonisation (ICH) Guidance Document: Good Clinical Practice: Integrated Addendum to E6(R1) ICH Topic E6(R2) in the Canadian context.”

BEFORE BEGINNING THE STUDY

OBTAINING ETHICS APPROVAL

This link contains guidance notes and instructions in accessing RISe (Researcher Information Services), the UBC online tool to manage and track your ethics application and funding support information online. Note you must have a UBC CWL to start. Instructions for obtaining a CWL are also located here.

The PHC REB generally meets the last Friday of every month, and applications must be submitted three weeks in advance. For meeting dates see here.

OBTAINING ORGANIZATIONAL/INSTITUTIONAL APPROVAL
CONTRACTS

Any contract or agreement necessary to start your research study should be run through the PHCRI contracts office. This includes confidentiality agreements, sub-site agreements, or industry clinical trial agreements, among others. Contact Esther Wu (Manager, Clinical Research Contracts and Grants) for further information.

There are some common medical-legal issues that arise in the context of clinical trials. The Canadian Medical Protective Association (CMPA) released a document recently that describes some of the issues with respect to clinical research contracts. See here for more information.

ESSENTIAL DOCUMENTS FOR CLINICAL TRIALS

Good Clinical Practice (GCP) is an international standard for the design, conduct, performance, recording, analyzing, and reporting of research that involves human participants. Ultimately GCP are in place to protect the rights, safety and welfare of humans participating in research, and to assure the quality, reliability, and integrity of data collected. All members of the research team (investigators, sponsors, and research ethics boards) are required to follow GCP.

All Health Canada regulated clinical trials require maintenance of essential documents. It’s strongly recommended that all non-regulated research studies maintain these documents to comply with GCP guidelines. These documents are generally filed in the Trial Master File (sponsor), or the site regulatory file (site level). To assist you, included in the following list of required documents are templates that can be used/modified for investigator-initiated studies and sponsored studies as well.

A list of Essential Documents and their purpose can be accessed here.

Suggested logs for clinical trials:

Current CVs and practice licenses (as appropriate) should be maintained to show the qualifications of the study team.

TRAINING AND STANDARD OPERATING PROCEDURES (SOPs) FOR CLINICAL RESEARCH STUDIES

As indicated above (see: Obtaining Ethics Approval), the PHC REB requires that the course on research ethics be completed by all study team members, prior to receiving REB approval.

Through B.C.’s membership in the Network of Networks (N2) you have access to many other required training courses.

You must complete, at a minimum:

  • GCP training. Note: Health Canada does not define how frequently GCP training should be completed, but in general, sponsors require re-training every two years (N2 offers a refresher course). Check with the institution you signed up with for their specific retraining requirements.
  • If shipping specimens is included in your protocol, all personnel conducting the shipping must complete the Transportation of Dangerous Goods certification.

Recommended:

  • Division 5 training (required for regulated studies)
  • Responsible Conduct of Research (RCR)

Membership in N2 also provides access to a set of clinical research Standard Operating Procedures (SOPs). Contact Julie Hadden, Erin Cherban, or Leslie Love if you need access to these. At a minimum, at the site level, you should have the following SOPs for a Health Canada regulated clinical trial:

  • Informed Consent Process
  • Serious Adverse Drug Reaction Reporting
  • Research Team Training
  • Equipment Calibration and Maintenance
  • Long-term Storage of Study Documents
  • Management of Investigational Product (if applicable)
TRIAL REGISTRATION REQUIREMENTS

Any clinical study involving human participants must be registered on a public clinical trial registration website. The most commonly used is clinicaltrials.gov. UBC provides assistance for UBC researchers. See here for assistance in getting your study registered.

OTHER ITEMS TO CONSIDER

DEFINING ROLES AND RESPONSIBILITIES

If you are acting as sponsor-investigator for a multi-centre study, or you are receiving some support from an industry partner, it is suggested to document who is responsible for each study activity. This is often required when negotiating a contract with another institution.

HUMAN RESOURCES

You may wish to conduct a needs assessment in advance to determine your human resource requirements to perform the study. For example, how much work will this study entail and what sort of training is required? For Health Canada regulated clinical trials, you are required to conduct this needs assessment prior to hiring staff.

You are legally obligated to ensure that both you and your staff have sufficient time to conduct the trial, and that all personnel affiliated with the trial are sufficiently trained for their position and their duties during their trial. CHÉOS can help you in this assessment. We also have many qualified research coordinators/assistants on staff who may be able to provide assistance. Contact researchsupport@cheos.ubc.ca for further information.

DATA COLLECTION AND MANAGEMENT

What type of database do you need to collect your data? Evaluate the scope of data to be collected as that will drive the decision. For example, interventional studies are better suited to an electronic data capture (EDC) platform like Inform while observational studies may utilize an EDC platform like REDCap. REDCap is also suitable for web-based surveys.

It’s always a good idea to create data collection worksheets for each study visit to ensure all required data elements are collected. Here are a couple of examples of data collection worksheets that are generally included in all clinical research studies: physical exam and demographics.

MONITORING PLAN AND STATISTICAL ANALYSIS PLAN (for multi-centre studies)

For Health Canada regulated clinical trials, you are required to provide oversight on the study to ensure it is conducted in accordance with the protocol, SOPs, GCP, and local requirements. Generally, this is completed by either onsite monitoring of study sites or remote monitoring through the data collected. The purpose of monitoring is to ensure the rights and wellbeing of participants are maintained, and that the data collected are accurate, complete, and verifiable from source documents (GCP 5.18.1). The extent and nature of monitoring will depend on the study. CHÉOS provides a monitoring plan template; contact Erin Cherban or Leslie Love to access the templates.

A statistical analysis plan (SAP) is created to define the details of the planned statistical analysis for your research study. It should be created before the research starts. It usually includes sample tables and listings of data, the manner in which the datasets will be analyzed, and methods for protocol deviations, unblinding, and how to deal with missing data. The SAP needs to be created by a statistician with experience in clinical trials.

RISK MANAGEMENT PLAN

The 2016 ICH E6 (R2) Addendum to Good Clinical Practice guideline requires clinical trial sponsors to incorporate a risk management plan as part of clinical trial activities. Risk Management allows the study team to identify areas where issues may occur in a clinical study, and incorporate strategies to prevent issues from impacting the study’s successful completion. For further information see our Risk Management 101 overview.

PROJECT EXECUTION

CONDUCT THE STUDY/PROJECT

Recruitment

Recruitment and participant retention can be the most challenging aspect of any clinical research study. A potential study participant may meet all the inclusion/exclusion criteria, but find the time commitment too onerous, the study too complicated, or be worried about how participation may affect their disease. You should have a realistic recruitment plan in place: site databases, social media, and print advertising are just some suggested recruitment strategies. Note that any recruitment materials must be approved by the REB.

Monitoring, Audits, and Inspection

Monitoring is considered the oversight, or quality review, of the study as it progresses to ensure it is being run in compliance with the study protocol, GCP, and local regulations. Generally, monitoring is ongoing throughout the study. Similar to monitoring, the purpose of an independent audit is to ensure the investigator is in compliance. All clinical studies can be audited by the local REB or by the study sponsor. In addition, all Health Canada regulated studies are potentially subject to inspections and/or audits by Health Canada. If you are notified that your study is subject to an audit or inspection, contact Erin Cherban, Chief Clinical Research Officer, CHÉOS/CTN.

ANALYZE THE DATA

Once the study is complete, you will need to contact a biostatistician (preferably the one who created the statistical section in the protocol, or the statistical analysis plan in regulated studies) to analyze the data.

DISSEMINATE/PUBLISH THE DATA
  • For designing conference posters, see here.
  • If you decide to publish a manuscript, each journal has their own format and guidelines for manuscript preparation. For general rules, the EQUAtor website has a searchable database for reporting guidelines.
  • Knowledge Translation is the term used when moving the data generated in research into the hands of the organizations that use it. Fraser Health has an excellent toolkit on how to implement research findings into clinical practice.
  • CIHR resources on knowledge translation and synthesis and knowledge user engagement.
  • CHÉOS also provides support for Knowledge Translation.
STUDY CLOSURE AND ARCHIVING

If your study is a clinical trial regulated by Health Canada, you are required by Health Canada to retain study documents for 25 years after trial completion. UBC now offers records managements/storage services at a reasonable cost. Iron Mountain and Butler Box and Storage also offer record management services.

If your study is not a clinical trial, you should retain your records per institutional requirements. For UBC, this is five years after study publication or presentation.

You must close the study with the PHC REB, and if you have received outside funding you usually need to report back to the funding agency as well.

FURTHER INFORMATION

Providence Health Care Research Institute

UBC Research Ethics

UBC Office of Research Services

Network of Networks Canada

Health Canada Clinical Trials Information

For a more in-depth overview of particularly important aspects of the clinical research process, please see our Clinical Research 101 Series, a set of articles written by our Project Management staff and other local experts.

Health research in the heart of Vancouver

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