Designing and budgeting a clinical trial can feel daunting once your research concept has been endorsed, especially when facing regulatory, budgeting and operational questions for the first time.
This guide walks you through the essential steps to create a budget and conduct a clinical trial in Australia, from identifying your Sponsor and trial centre to planning data management, drug supply, safety oversight and protocol development, ensuring your study is feasible and ready for funding.
Identify your Sponsor and trial centre
The clinical trial Sponsor will have requirements under Good Clinical Practice (GCP). In an IIcT or Investigator-initiated clinical trial, a pharmaceutical company is never the Sponsor. TOGA also does not take on the role of clinical trial Sponsor. The Sponsor is responsible for the accuracy of the protocol and for the safety and accuracy of the clinical trial, and will enter into contracts with the site. Usually, the funding body, will make site payments (unless delegated to the trial centre) and will need to obtain clinical trial insurance. This is not a comprehensive list of Sponsor obligations; these can be found in ICH GCP E6 and subsequent amendments.
The Sponsor needs to be comfortable that their risks are mitigated, so they will likely have some views on other trial decisions such as trial centre, site selection, data management, drug distribution, budget and how you intend to oversee safety. Engaging the Sponsor is key to feasibility of your clinical trial operations and budget. If you are using a trial centre, you will need to request a quote. You can request the centre’s quote form, or assemble your thoughts using ‘TOGA’s Multisite investigator-initiated trial cost drivers description”.
Regulatory notification
In Australia, this is generally an application through the Clinical Trial Notification (CTN) system if you need to supply drug as clinical trial supply (i.e. not under a marketing licence). You can check if a drug has a relevant marketing licence under the ARTG.
Note: drugs can have marketing licences, even if they are not on the PBS.
Drug supply
Determine if drugs are PBS-supplied or need to be provided as part of the trial; if supplied, determine if study funding must cover an Australian depot to receipt and distribute drug, forecasting, and any type of labelling and QA release costs. Most site pharmacies will not hold large quantities of drugs, especially if recruitment is slow. This may increase your drug transport frequency. You can quote the cost of these services with Australian drug depots. Consider how you will meet the obligation to provide ongoing supply beyond the trial if a patient is continuing to receive benefit.
Trial master file (TMF)
This is all the documentation related to the clinical trial. It has a defined structure and must be kept up to date and kept for the relevant archiving period. Maintenance of this will be part of your trial centre quote.
Data management
This is a significant component of your trial budget, and rightly so. Without clean and complete data, you cannot draw conclusions from your trial, or you may draw inaccurate conclusions. If you have engaged a trial centre, they will likely provide data management as part of their quote, which probably includes collection, cleaning and source data verification.
- Data collection: This is most commonly done on electronic Case Report Form (CRFs) linked to a database through a provider such as MediData Rave or accomplished through REDCap. Licensing and cloud storage fees may apply. Ensure you know the location of your cloud storage to satisfy Australian privacy requirements for health-related data.
- Data cleaning: This involves field validations, e.g., numeric character only, or an upper allowable limit, and cross-field validations (can be pre-programed or done manually). In an electronic data capture system, programmed checks may raise data queries immediately, whereas manual checks usually need to be raised in the system. Some of these checks may also be run on aggregated data to identify and validate outliers. If manual checks are required, and you are using a trial centre, this will be part of their quote.
- Source data verification (SDV): Commonly undertaken by site monitoring, this type of check is the most expensive way to ensure clean data, and other options should be considered first. It is usually limited to key outcome fields and eligibility. In recent years, remote monitoring has increased. If you rely on SDV, ensure you have access to the site and any electronic health records needed.
- Data Access and Analysis: If you need access to demographic data for laboratory studies before the primary analysis, arrange this early. Most trial centres will only allow data to be accessed before primary analysis in extreme circumstances. Analysis of clinical trial data must be undertaken by suitably qualified individuals, e.g., a statistician who will likely need access to a statistical package. There is also a growing need for access to secure research environments for certain analyses. Ensure these costs are part of the trial centre quote or elsewhere accounted for in the budget.
Safety oversight
The clinical trial Sponsor is responsible for safety oversight. Depending on the type of clinical trial, they may rely on a team of investigators and a statistician to review safety reports (Serious Adverse Event (SAE), international SUSAR (Suspected, unexpected, serious adverse drug reaction) line listings) and any other emerging data that could impact on safety (e.g. scientific literature, Investigator’s Brochure (IB)). This committee may be called a DSMB, and IDSMC or a SDMC.
The committee should have a Terms of Reference detailing composition, appointment, role of the Chair, and any other specialist members’ data to be made available, frequency of reviews and how decisions are made. Conflicts of interest need to be managed. Consider whether this committee will have expenses, e.g., for meetings or travel. SAEs need to be reviewed in real time to assess if they qualify as SUSARs, promoting notification to the TGA. This is usually part of the trial centre quote.
Real time review of SAEs for causality and expectedness is also a Sponsor responsibility but often delegated to a team of lead investigators in an IIcT. The causality assignment from the site investigator can only ever be upgraded centrally, and expectedness is determined by comparison to the Investigator’s Brochure (IB) or Product Insert. SAEs that are unexpected and related to the drug are commonly referred to as SUSARs and require reporting to the TGA according to strict timeframes.
Laboratory studies
It is important to determine sample collection, processing, shipping and storage for your budget.
If samples can be processed on site, they can usually be stored frozen and batched in one shipment at the end of the clinical trial. Do not write arrangements for laboratory studies in the protocol, but prepare a separate lab manual that does not need to go to HREC. This gives extra time to prepare this document, and also means that changes in lab samples or processing will not incur a protocol amendment. In some studies, specialised collection tubes and kits are sent to sites. Ensure you have storage space for consumables and resource for packing and distributing kits factored into your planning if this is needed.
Site management
- Site feasibility survey and site selection: It is important to select a network of sites that have adequate facilities, can deliver on recruitment and span a geographical breadth to ensure sufficient diversity in your population and treating centres to facilitate translation of clinical trial results. For endorsed studies, TOGA cand send site feasibility surveys to their membership. To plan a site feasibility survey, use the Site Feasibility Questionnaire Master.
- Ethics and governance: A lead site for the submission needs to be identified. The lead site traditionally attracts a higher payment. Governance fees likely also apply but could be incorporated into a site start-up payment to be negotiated in the site contract. This start up payment is made to the site regardless of patient recruitment, and goes some way to off-setting setup costs.
- Site contracts: Clinical trials usually use the Medicines Australia Clinical Trial Research Agreement (CTRA). For clinical research not providing a novel intervention, the Collaborative research agreement template – for projects not involving clinical trials may be useful.
- Per-patient payments: TOGA can provide guidance on typical per-patient payments used in TOGA trials.
- Pharmacy fees: These are not always waived for IIcTs but are usually paid as part of the per-patient payment. You may need to prepare a pharmacy manual.
- Site monitoring: An assessment of risks in study conduct and of inaccurate data collection will be undertaken by the Sponsor and will usually determine the need for central (remote) vs on-site monitoring. As well as source data verification, an on-site monitoring visit generally involves a check with pharmacy to ascertain drug accountability and existing stocks of investigational product, a review of the Investigational Site File a meeting with the site PI and on site study team to answer questions or communicate important updates, and verification of consent documentation.
Close out activities and archiving
Participating sites in a clinical trial need to be formally closed out at the conclusion of their participation. They will likely require a summary of the trial results for submission to HREC and distribution to participants. When closed out, sites may ask to transfer the Investigator Site File to central storage, incurring archiving costs.
In addition, the TMF and the trial data will need to be stored for a certain period, incurring archiving costs. Digital and paper storage may apply.
Writing a protocol
Don’t rush into this step.
Focus on getting the design right first. New investigators may consider the MOGA ACORD workshop that provides expert guidance to work an idea into a protocol. If you’re not sure where to start, fill out the protocol synopsis first as a prompt for the information required. If you are using a trial centre, they will most likely provide you with their own protocol template. Writing the protocol may be part of the trial centre quote. Download a generic protocol template or use the SPIRIT protocol checklist.
- Assessments for response and safety: These form the study visit/assessment schedule in the protocol. Clarify which tests and procedures are standard. Costs for additional tests are typically built into the per-patient payment.
- Central reviews: If applicable, these may be for imaging, pathology, or molecular reviews, and there may be costs for provision of review services or infrastructure to facilitate reviews.
- Biostatistics Generally a statistician will write the statistical section of the protocol, formed by the initial discussion over sample size calculations you had during study design. They may require additional payment for this work.
- Protocol and PICF amendments: Factor these into your trial costs. PICF amendments generally arise due to newly emerging safety data and will incur central management and HREC costs. Generally, sites re-consent at no extra cost to the IIT, but it’s important not to stretch the goodwill of site teams. Protocol amendments can be avoided if the protocol is well planned from the outset. Keep non-critical information out of the protocol (e.g. lab sample processing details can be in a manual, exploratory studies can be described more generally).
Many of the above also apply if you are planning to bring an international trial to Australia to open at multiple sites. You will still need a local Sponsor, but the international Sponsor will provide the electronic data collection and data management procedures, the analysis, the publication, as well as overall safety review. However, the local sponsor is still responsible for local safety obligations in clinical trials, and you will still need some central coordination resource, and a central contact for the International Sponsor operational staff. The local Sponsor will most likely enter into an agreement with the international Sponsor. For more information on how to set up an international trial, see the checklist for division of responsibilities in international trials to start your conversation with the international trial Sponsor.
Key takeaways: Turning a concept into a clinical trial
- Engage your Sponsor early: Clarify who will hold legal responsibility under GCP and ensure risk mitigation processes are in place.
- Select a capable trial centre and obtain a detailed quote covering data management, safety oversight, and trial master file maintenance.
- Plan your regulatory pathway: Confirm if a CTN submission to the TGA is required and check marketing licence status on the ARTG.
- Budget comprehensively: Include drug supply logistics, data collection systems, monitoring, DSMB activities, archiving, and site start-up fees.
- Protect data quality: Specify how data will be captured, validated, and cleaned; identify who will perform analysis.
- Define safety oversight: Establish a DSMB or equivalent committee with clear Terms of Reference and conflict-management processes.
- Prepare robust supporting documents: Create a separate laboratory manual, pharmacy manual, and site feasibility survey.
- Write the protocol last: Finalise the design and budget first, then develop the protocol using the SPIRIT checklist or TOGA template.
- Consider international collaborations: Clarify local Sponsor responsibilities and agreements when opening global studies in Australia.
- Use TOGA resources: Access protocol templates, site feasibility questionnaires, and quote prompts to streamline trial setup.
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