**3. Requirements for implementation of the tele-trial model**

Satellite sites (regional, rural or metropolitan) would vary in their capability to conduct trials based on resources and prior experience. Based on the capabilities of the satellite sites, primary sites may delegate to the satellite sites some or all aspect of trials, in agreement with the sponsors and satellites.

#### **3.1. Selection of satellite sites and suitable trials**

Site feasibility assessments may have to consider the capability of the whole cluster and potential satellite sites are indicated during the site feasibility process. This informs the trial Sponsor of the referral relationship between the primary site and satellite sites within the cluster. The cluster may include hospitals within the same region, network or local health district or hospitals in other regions, networks and local health districts. Once the primary site is chosen, the acceptance of the satellite sites by a trial Sponsor will depend on the prior experience of the satellite site in conducting clinical trials, the complexity of the trial, and the medical, nursing, allied health, pathology and pharmacy research capabilities. Site capacity and trial complexity will determine the ability of the site to conduct trial-related activities at the satellite site and will be assessed by the Sponsor at the time of site selection. It is not anticipated the satellite site will undertake all trial-related activities. Satellite sites that have established trial capabilities are able to take part in complex protocols from the outset. At sites that have no or limited experience in delivering clinical trials, a staged approach may allow for gradual building of clinical trials capacity from simple to more complex trials.

#### *3.1.1. Accreditation of satellites*

For sites that have not taken part in clinical trials previously, as required under current practice, it is likely that the Sponsor may wish to perform a site visit. The Sponsor may also wish to delegate this responsibility to the primary site.

#### *3.1.2. Supervision plan*

researchers. This may have flow-on benefits for improved access to trials and improved quality of care. There are also advantages for Australia to develop a more flexible approach to the conduct of trials; given our relatively small population and geographic barriers to recruitment. Recruiting specific patient cohorts is an ever-present challenge. Without multisite collaboration, Australia is less attractive to international trial Sponsors, which limits the availability of experimental, life-saving treatments. Developing these clinical trial networks through models like this tele-trial concept, we can better promote our capacity to support a wider range of

Tele-trials offer the unique opportunity to impact this inevitable cascade of circumstances that compound the difficulties of defining new treatments for so many cancers in the modern era

While the benefits discussed above have positive flow on effects on patient care and the Australian Health system as a whole, system improvement using this model is unlikely to be achieved without added cost for the sponsors (including increased site visits, medication transport cost to satellites, etc.), hospitals and governments (increased workforce, technological and pharmacy infrastructure). Benefits of improved rural access to clinical trials and enhanced rate of recruitment can offset those extra costs. Reforms on remote monitoring, site accreditation, ethical, governance and contractual processes are required at a system level to

Geographic isolation due to distance may cause several problems including workforce stability, transporting and handling of medications and devices, access to source documents and communication between sites which can be mitigated by implementing the processes

Satellite sites (regional, rural or metropolitan) would vary in their capability to conduct trials based on resources and prior experience. Based on the capabilities of the satellite sites, primary sites may delegate to the satellite sites some or all aspect of trials, in agreement with

Site feasibility assessments may have to consider the capability of the whole cluster and potential satellite sites are indicated during the site feasibility process. This informs the trial Sponsor of the referral relationship between the primary site and satellite sites within the cluster. The cluster may include hospitals within the same region, network or local health district or hospitals in other regions, networks and local health districts. Once the primary site is chosen, the acceptance of the satellite sites by a trial Sponsor will depend on the prior experience of the satellite site in conducting clinical trials, the complexity of the trial, and the medical,

of molecular characterisation of cancer across regional and rural Australia.

**3. Requirements for implementation of the tele-trial model**

trials.

**2.2. Anticipated costs and threats**

162 Clinical Trials in Vulnerable Populations

reduce financial and human resource cost.

outlined in this document.

the sponsors and satellites.

**3.1. Selection of satellite sites and suitable trials**

Some registration bodies require that the primary site Principal Investigator (PI) take responsibility for overall supervision of the trial across a cluster. Tele-health offers a unique opportunity for direct supervision of patient management. A supervision plan agreed between the primary and satellite sites and the Sponsor needs to be developed and formalised at the outset of a trial. The supervision plan may include, but not be limited to, details on joint consultations using tele-health, collation and monitoring of documents, frequency of joint trial meetings across a cluster (with minutes of these meetings) and any site visits performed by the PI.

#### *3.1.3. Site visits*

While the travel by staff and patients is reduced as the result of this model, Sponsors may wish to undertake site visits for accreditation and monitoring purposes, unless remote monitoring is agreed by the Sponsor and source documents are available at the primary site.

#### **3.2. Workforce: roles and responsibilities**

The workforce requirements of current tele-health models could be extended to the tele-trial model. While larger rural and regional centres may have resident or visiting medical oncologists, oncology clinicians and trial nurses, satellite sites may have limited specialised services. Under the current tele-health models, urban specialists at a primary site provide their services using videoconferencing. Service delivery is supported and facilitated by doctors, nurses and allied health professionals at a satellite site. The nature of support to and by the rural health professionals would be determined by the complexity of the trial and the clinical capabilities at the site [22, 23]. The delegated responsibilities would need to be agreed by the Sponsor, clearly documented within the master site file and trial-related training records provided before this delegation could occur.

Defining roles and allocating specific responsibilities to staff within a cluster can ensure the safe and efficient conduct of clinical trials. The satellite team would need to take part in the Investigator Meeting & Study Initiation Visit so that they are fully aware of the requirements for compliance with the Investigational Brochure (IB), study protocol and the importance of these required processes. Tele-health technologies offer the opportunity to conduct investigator meetings and study initiation visits across geographically dispersed clusters. This is particularly important for reporting and managing adverse events and serious adverse events, and ensuring that patient reported outcomes are completed in a timely manner without excessive missing data.

**8.** Develop arrangements for radiology and pathology reviews and for engagement with other clinicians including genetic counsellors, other specialists and allied health professionals,

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Satellite site medical officers will be the local contact for trial-related matters within a satellite unless the PI and the primary site agree to take this responsibility. Depending on the prior experience of satellite site investigators and satellite capabilities, the PI may delegate some or

**2.** Satellite sites would require monitoring visits to review source documents that are not entered into an electronic medical record (EMR) system or shared between the satellite site

**7.** Timely communication and management of AEs and SAEs and study reporting in collabo-

**8.** Develop arrangements in collaboration with the PI for radiology and pathology reviews and for engagement with other clinicians including genetic counsellors, other specialists

**9.** Develop plans for local contacts during periods of cover for holidays and unexpected leave.

Trial co-ordinators at primary sites act as a contact for coordinators at both the primary and

**2.** Collate and coordinate documentation from satellite sites including the preparation of

**5.** Manage the regulatory processes and reporting requirements to the trial Sponsor, and hu-

and allied health professionals, as dictated by trial protocols, within their site.

as dictated by trial protocols, across a cluster.

**6.** Undertake activities related to study follow-up.

all of the trial-related responsibilities to the satellite site investigators:

**3.** Undertake ICH-GCP accreditation and training on the study protocol.

**5.** Manage, store and dispense CTIMP if required and accredited to do so.

**1.** Coordinate the study and monitor progress across the cluster.

**3.** Identify staff changes and initiate appropriate training.

**4.** Conduct trial meetings by including satellite sites.

man research ethics committees as required.

**1.** Conduct joint trial visits with primary sites when required by the trial Sponsor.

**4.** Take part in the consenting process, perform and document physical assessments.

*3.4.2. Satellite site investigators*

and primary site.

ration with primary sites.

*3.4.3. Trial co-ordinators*

satellite sites.

CRFs.

#### **3.3. Good clinical practice**

All clinical trials involving Clinical Trial of Investigational Medicinal Products (CTIMPs) must be conducted according to the principles of International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and local laws for Good Clinical Practice (GCP). ICH and GCP requirements, local laws and regulations and the Sponsors' protocol and company requirements as outlined in the Australian legislative requirements applying to prescription medicines are contained in the Therapeutic Goods Act 1989 and the Therapeutic Goods Regulations 1990.

#### **3.4. Roles and responsibilities of trial site staff**

Prior experience of staff and capabilities of the satellite sites would determine the roles of the satellite trial staff. PI may delegate some or all of the trial-related processes to the satellite site staff, in agreement with the sponsor and satellite staff. It is important that roles and responsibilities are agreed and formalised at the outset.

#### *3.4.1. Primary investigator at primary sites*

Some registration bodies require that the PI is responsible for overall supervision of the trial, including satellite sites. Therefore, it is important to develop a supervision plan including cover for holidays and unexpected leave at the outset of a trial and incorporate this into the contract.


**8.** Develop arrangements for radiology and pathology reviews and for engagement with other clinicians including genetic counsellors, other specialists and allied health professionals, as dictated by trial protocols, across a cluster.

### *3.4.2. Satellite site investigators*

for compliance with the Investigational Brochure (IB), study protocol and the importance of these required processes. Tele-health technologies offer the opportunity to conduct investigator meetings and study initiation visits across geographically dispersed clusters. This is particularly important for reporting and managing adverse events and serious adverse events, and ensuring that patient reported outcomes are completed in a timely manner without

All clinical trials involving Clinical Trial of Investigational Medicinal Products (CTIMPs) must be conducted according to the principles of International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and local laws for Good Clinical Practice (GCP). ICH and GCP requirements, local laws and regulations and the Sponsors' protocol and company requirements as outlined in the Australian legislative requirements applying to prescription medicines are contained in the Therapeutic

Prior experience of staff and capabilities of the satellite sites would determine the roles of the satellite trial staff. PI may delegate some or all of the trial-related processes to the satellite site staff, in agreement with the sponsor and satellite staff. It is important that roles and responsi-

Some registration bodies require that the PI is responsible for overall supervision of the trial, including satellite sites. Therefore, it is important to develop a supervision plan including cover for holidays and unexpected leave at the outset of a trial and incorporate this into the contract.

**1.** Participate in trial consultations with satellite site medical officers via tele-health if required. **2.** Take part in the consenting and recruitment process remotely or on-site as required via

**4.** Provide oversight of SAE reporting, ensuring satellite sites provide source documents and

**5.** Be available to consult on the management of Serious Adverse Events and adverse events

**7.** Ensure all staff at both the Primary and Satellite Site are trained in the trial specific activi-

**6.** Maintain a delegation log for all research staff at both primary site and satellite sites.

**3.** Communication with satellite investigators regarding protocol revisions,

Goods Act 1989 and the Therapeutic Goods Regulations 1990.

**3.4. Roles and responsibilities of trial site staff**

bilities are agreed and formalised at the outset.

*3.4.1. Primary investigator at primary sites*

tele-health.

reports as required.

(SAE/AEs) as required.

ties delegated to each.

excessive missing data.

164 Clinical Trials in Vulnerable Populations

**3.3. Good clinical practice**

Satellite site medical officers will be the local contact for trial-related matters within a satellite unless the PI and the primary site agree to take this responsibility. Depending on the prior experience of satellite site investigators and satellite capabilities, the PI may delegate some or all of the trial-related responsibilities to the satellite site investigators:


#### *3.4.3. Trial co-ordinators*

Trial co-ordinators at primary sites act as a contact for coordinators at both the primary and satellite sites.


#### *3.4.4. Pharmacy and pharmacy facilities*

Trial Sponsors may elect to deliver CTIMP directly to the site, dispensing the CTIMP and maintain drug accountability documentation at the site. Sponsors may delegate this responsibility to the primary sites. This requires the primary and satellites sites to work together collaboratively. Both the primary and the satellite site(s) would need to ensure that adequate documentation is in place to allow full drug accountability and be suitably qualified to undertake the following:

**10.** Regular temperature monitoring of CTIMP storage facilities should be undertaken and records maintained for both primary and satellite sites. All CTIMP storage areas should be fitted with calibrated temperature monitoring devices that record minimum and maximum temperatures, with a robust system to alert staff if the temperature falls outside of the specified range. The temperature monitoring devices should have a valid calibration certificate which is maintained for reference. The pharmacy should have written procedures in place for the actions to be taken when the storage conditions are outside of the

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**11.** Pharmacies should have an approved destruction policy that outlines the process for destroying; although some Sponsors may require unused, expired or returned CTIMP study medication to be returned to a Sponsor nominated central licensed facility for

**12.** Pharmacy files will be kept by the primary site and where requested, may develop ad-

**13.** Suitable archiving facilities will be required for pharmacy trial files. The system used for archiving must allow for prompt retrieval of any pharmacy study file or of non-study specific documentation (such as pharmacy standard operating procedures, original phar-

**14.** Pharmacy should receive funding for providing a clinical trial service. This funding should reflect the workload and cover costs involved and is separate to the prescription

**15.** Procedures for unblinding must be made available to the satellite site in the case of an

The patient compliance with taking the medication will be monitored by the dispensing pharmacy, nursing and medical officers. During joint consultations, primary site clinicians can

Pathology and radiology requirements are dealt with at the feasibility questionnaire stage and arrangements agreed by Sponsors. Biopsy and biomarker and pharmacodynamic studies may require onsite centrifuge, processing and storage. If the satellite site does not have these capabilities, private pathology could be used and considered subcontractors or agents of the primary site in agreement with the Sponsor. Similar arrangement could be made for radiology requirements. For sites that have never participated in trials, the Sponsor may wish to

Training requirements are the same for both the primary and satellite site staff involved in

macy temperature monitoring records and training records of pharmacy staff).

ditional accountability logs and files for satellite site usage.

specified range.

destruction.

charge.

**3.5. Training**

emergency.

also reiterate to patients.

*3.4.5. Pathology and radiology*

clinical trials within a cluster.

conduct a site visit to assess these aspects.


The patient compliance with taking the medication will be monitored by the dispensing pharmacy, nursing and medical officers. During joint consultations, primary site clinicians can also reiterate to patients.

#### *3.4.5. Pathology and radiology*

Pathology and radiology requirements are dealt with at the feasibility questionnaire stage and arrangements agreed by Sponsors. Biopsy and biomarker and pharmacodynamic studies may require onsite centrifuge, processing and storage. If the satellite site does not have these capabilities, private pathology could be used and considered subcontractors or agents of the primary site in agreement with the Sponsor. Similar arrangement could be made for radiology requirements. For sites that have never participated in trials, the Sponsor may wish to conduct a site visit to assess these aspects.

#### **3.5. Training**

*3.4.4. Pharmacy and pharmacy facilities*

166 Clinical Trials in Vulnerable Populations

are under consideration by the primary site.

provide up-to-date GCP training records.

take the following:

types of products.

to ensure traceability.

ing stock.

annotated guidelines annex 13.

certified and reach GMP standards etc.

able to participate in trials with this requirement.

Trial Sponsors may elect to deliver CTIMP directly to the site, dispensing the CTIMP and maintain drug accountability documentation at the site. Sponsors may delegate this responsibility to the primary sites. This requires the primary and satellites sites to work together collaboratively. Both the primary and the satellite site(s) would need to ensure that adequate documentation is in place to allow full drug accountability and be suitably qualified to under-

**1.** The primary site pharmacist is responsible for overall service provision in collaboration with satellites, i.e. receipt of the IP, storage and handling, dispatch to satellite or trial participant, reconciliation and communicating the management of IP with the satellite site. The primary site pharmacist will be the first point of contact when trials involving CTIMPs

**2.** Designated pharmacy staff providing a clinical trial service must be adequately qualified, trained and experienced to assume clinical research responsibilities and should be able to

**3.** The pharmacy must hold training records and signature logs for those staff involved in a clinical trial in the pharmacy department. These will be held at the site and should include all staff involved at either the primary site or satellite sites. These records may also be held

**4.** Appropriate facilities should be available before agreeing to support a clinical trial particularly one involving radiopharmaceuticals or Advanced Therapy Medicinal Products (ATMPs) such as gene therapy and cell therapy. The pharmacy lead site for clinical trials should liaise with, and seek advice from, satellite sites with experience in handling these

**5.** The institution (pharmacy department) is required to hold a GMP licence as per the TGA

**6.** Manufacturing must be performed to GMP and release performed by a Qualified Person in certain circumstances labelling may be performed at a site but the facilities have to be

**7.** If the satellite site does not have access to a local GMP qualified facility they would not be

**8.** Pharmacies should have facilities that allow for CTIMPs to be stored separately from normal pharmacy stock in an area with access restricted to pharmacy staff. Licensed products used as CTIMPs do not have to be stored separately as long as there is a process in place

**9.** CTIMPs that are returned by patients or expired should be stored separately from unused CTIMPs. Quarantined medication should be clearly identified and segregated from work-

in a central location and should be readily available for inspection if required.

Training requirements are the same for both the primary and satellite site staff involved in clinical trials within a cluster.

#### *3.5.1. Training for individual staff*

All investigators and trial staff at each site are required to have undertaken GCP training and certification. Individual staff members should ensure GCP competence is commensurate with their roles and responsibilities in relation to the study protocol and the management of CTIMPs. Whilst it may be the case that some staff carry out trial-related tasks that are part of their normal role, they should be certified in the principles of GCP. A mentorship program would be of benefit where staff from the satellite sites have the opportunity to observe and have hands on experience at the primary site is one such example. Primary and satellite staff training is required to ensure that staff are competent to participate in the conduct of, or for providing the supporting and delegated activities of, a clinical trial. Both the primary and satellite sites must retain training records and signature logs for those staff involved in the clinical trial. These records should be readily available for inspection if required. GCP training can be accessed through the Australian Clinical Trials website: https://www.australianclinicaltrials.gov.au/researchers/good-clinical-practice-gcp-australia

**3.8. Obtaining participant consent**

*3.8.1. Options for obtaining consent*

informed consent.

**3.9. Medication handling**

are completed.

outside of the bag of medication.

lowed by satellite site.

labelled and packaged for transport.

ated storage being transported from the primary site.

**f.** As per IB/Sponsor or manufacturers instruction.

on-site in a process approved by the Sponsor and the HREC.

Patients from satellite sites are screened and recruited and provide consent for trial participation in collaboration with doctors and nurses at primary and satellite sites using video-link or

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The process for obtaining consent remotely via tele-health or onsite would be reviewed by the Sponsor and approved by the HREC. Satellite sites can be delegated responsibility to obtain

For sites that do not have prior experience in clinical trials, it is important that the PI is directly involved in the trial consent process. In this option, the participants and the satellite site investigator sign the consent form, observed by an investigator at the primary site. This process is documented concurrently at both the primary site and satellite sites. At sites that have prior experience in trials, the satellite site investigator may be delegated to complete the consent process onsite. A copy of this final consent form can be given to the participant and stored in the medical record and in the primary trial site file. Mode of transfer for these documents (fax, emails and/or post) needs to be agreed by the Sponsor according to their privacy policies.

Sponsors may prefer to deliver CTIMP or devices directly to primary and satellite sites to reduce the cost of medication transport. At the request of the Sponsor, the primary site pharmacy may transfer clinical trial medication for administration or collection to satellite sites. Medications may include the investigational product and/or non-investigational medications related to the clinical trial. The following Sponsor approved medication could be managed in the following way:

**a.** Medication is dispensed and/or prepared according to protocol and accountability logs

**c.** An acknowledgement of receipt form and a copy of the prescription are attached to the

**d.** The bag of medication is placed into a suitable container (e.g. box or padded envelope) and

**e.** Cold pack and temperature monitor should be included for medication requiring refriger-

**g.** Completed CTIMP containers being returned to the primary site are not required to be temperature-monitored. However, if a temperature-monitoring device is supplied by the Sponsor, the primary pharmacy will include it with the parcel with instructions to be fol-

**b.** Medication is sealed in a non-transparent bag clearly labelled with the patient details.

#### *3.5.2. Site initiation and trial update*

Site initiation meetings and site staff training on the trial protocol for primary and satellite sites in a cluster could be undertaken via videoconferencing across a large geographical area. Site initiation meetings could also be used to reiterate the roles and responsibilities of staff across all sites. Joint consultations and regular trial meetings are also useful forums for discussing trial-related matters and updates.

#### **3.6. Technology and support**

A web-based system or videoconferencing equipment are required for interactive consultations. Availability of the electronic medical record (EMR) would enable seamless sharing of clinical data between sites. However, where the EMR is not available, source documents will need to be provided to the primary sites for data verification and trial monitoring purposes unless the Sponsor wishes to conduct trial monitoring visits themselves. While a tele-health approach may support the visit process both the primary and satellite sites need to understand the critical need for reliable source documents. In cases of technical failure, a secondary source of web-based technology should be available to ensure continuity of clinical encounters.

#### **3.7. Participant screening and recruitment**

It is expected that all processes and activities related to recruitment are coordinated by the primary site in communication with the satellite site. Satellite sites that have adequate resources could assist with screening and referral of patients for recruitment. Doctors, nurses and trial coordinators are able to identify patients, provide trial-related information and notify the primary sites, prior to participant consent being obtained.

NB: It is important to note that the National Statement has special requirements when enrolling special populations for example indigenous members of the community therefore sites need to ensure these requirements are met where appropriate.

#### **3.8. Obtaining participant consent**

*3.5.1. Training for individual staff*

168 Clinical Trials in Vulnerable Populations

*3.5.2. Site initiation and trial update*

**3.6. Technology and support**

cussing trial-related matters and updates.

**3.7. Participant screening and recruitment**

primary sites, prior to participant consent being obtained.

need to ensure these requirements are met where appropriate.

All investigators and trial staff at each site are required to have undertaken GCP training and certification. Individual staff members should ensure GCP competence is commensurate with their roles and responsibilities in relation to the study protocol and the management of CTIMPs. Whilst it may be the case that some staff carry out trial-related tasks that are part of their normal role, they should be certified in the principles of GCP. A mentorship program would be of benefit where staff from the satellite sites have the opportunity to observe and have hands on experience at the primary site is one such example. Primary and satellite staff training is required to ensure that staff are competent to participate in the conduct of, or for providing the supporting and delegated activities of, a clinical trial. Both the primary and satellite sites must retain training records and signature logs for those staff involved in the clinical trial. These records should be readily available for inspection if required. GCP training can be accessed through the Australian Clinical Trials website: https://www.australianclini-

Site initiation meetings and site staff training on the trial protocol for primary and satellite sites in a cluster could be undertaken via videoconferencing across a large geographical area. Site initiation meetings could also be used to reiterate the roles and responsibilities of staff across all sites. Joint consultations and regular trial meetings are also useful forums for dis-

A web-based system or videoconferencing equipment are required for interactive consultations. Availability of the electronic medical record (EMR) would enable seamless sharing of clinical data between sites. However, where the EMR is not available, source documents will need to be provided to the primary sites for data verification and trial monitoring purposes unless the Sponsor wishes to conduct trial monitoring visits themselves. While a tele-health approach may support the visit process both the primary and satellite sites need to understand the critical need for reliable source documents. In cases of technical failure, a secondary source of web-based technology should be available to ensure continuity of clinical encounters.

It is expected that all processes and activities related to recruitment are coordinated by the primary site in communication with the satellite site. Satellite sites that have adequate resources could assist with screening and referral of patients for recruitment. Doctors, nurses and trial coordinators are able to identify patients, provide trial-related information and notify the

NB: It is important to note that the National Statement has special requirements when enrolling special populations for example indigenous members of the community therefore sites

caltrials.gov.au/researchers/good-clinical-practice-gcp-australia

Patients from satellite sites are screened and recruited and provide consent for trial participation in collaboration with doctors and nurses at primary and satellite sites using video-link or on-site in a process approved by the Sponsor and the HREC.

#### *3.8.1. Options for obtaining consent*

The process for obtaining consent remotely via tele-health or onsite would be reviewed by the Sponsor and approved by the HREC. Satellite sites can be delegated responsibility to obtain informed consent.

For sites that do not have prior experience in clinical trials, it is important that the PI is directly involved in the trial consent process. In this option, the participants and the satellite site investigator sign the consent form, observed by an investigator at the primary site. This process is documented concurrently at both the primary site and satellite sites. At sites that have prior experience in trials, the satellite site investigator may be delegated to complete the consent process onsite. A copy of this final consent form can be given to the participant and stored in the medical record and in the primary trial site file. Mode of transfer for these documents (fax, emails and/or post) needs to be agreed by the Sponsor according to their privacy policies.

#### **3.9. Medication handling**

Sponsors may prefer to deliver CTIMP or devices directly to primary and satellite sites to reduce the cost of medication transport. At the request of the Sponsor, the primary site pharmacy may transfer clinical trial medication for administration or collection to satellite sites. Medications may include the investigational product and/or non-investigational medications related to the clinical trial. The following Sponsor approved medication could be managed in the following way:


**h.** The pharmacy at the receiving satellite site is contacted by telephone to notify them of the delivery.

Patients and their families need to be educated of the need for seeking urgent medical attention and reporting to the primary and/or satellite site staff of their concerns. Patients could also be given letters or brochures for communication with clinicians in an emergency situation. Not all situations may be able to be managed at the satellite site. Inter-hospital transfers may be required in consultation between primary and satellite medical officers in some cases.

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Some trials will include PROs, including quality of life endpoints, usually as secondary endpoints, but sometimes as primary. It is a matter of equity that rural and remote patients have the opportunity to self-report aspects of their health and quality of life as specified in the trial

PROs are typically assessed with questionnaires, either handed out to trial participants by the research nurse or completed online. The specific questionnaires, mode(s) of administration, and timing relative to recruitment and treatment need to be followed as per trial protocols. It is also important to develop mechanisms to minimise missing data as far as possible and

Many trials groups have reported success of centralised monitoring systems for maintaining high PRO completion rates. Staff should have access to ongoing training and written guidance

During trial consultations, a detailed patient history including the documentation of AEs and SAEs is obtained by doctors at primary or satellite sites or at both sites simultaneously. Results of investigations are available online at most centres. If results are not available online,

Physical examination may be performed by the doctor at the satellite site with or without observation by the primary site doctor and as per ICG-GCP the PI can only delegate to those with the necessary experience, training and qualifications. When joint medical consultations are conducted via tele-health, clinical encounters are documented at the site with the delegation to perform the specific study-related activity. If EMR is not available, certified copies of the source documents may be required and sent to the primary sites for monitoring purposes. Mode of transfer for these documents (fax, emails and/or post) needs to be agreed by the

Consideration also needs to be given to how satellite sites will be reimbursed for undertaking

There are administrative efficiencies if the co-ordination of invoicing or journal transfers for trial-related expenses at satellites sites are coordinated by the primary site. Generally most of

the primary site will ensure certified copies are provided by the satellite site.

trial specific procedures (e.g. blood tests; radiology procedures, etc.).

record reasons for missing data, so patient engagement is essential.

**3.11. Patient reported outcomes (PROs)**

and understand the importance of PROs.

Sponsor according to their privacy policies.

**3.13. Financial considerations**

**3.12. Documentation and reporting**

protocol.


#### **3.10. Managing and reporting adverse events (AEs) and serious adverse events (SAEs)**

#### *3.10.1. Management at routine clinics*

During planned trial consultations, the history of AEs and SAEs is obtained. Clinical trial staff needs to be aware that drug intervention studies will require minimum reporting times and the occurrence of AEs/SAEs are to be reported to the primary site in the usual within 24 hour plan by any satellite staff, medical practitioner, nurse or data manager. SAEs are managed according to the protocol and documented in the EMR or medical charts by medical specialists/medical officers at satellite sites. If EMR is not available, certified copies of the source documents may be required and sent to the primary sites for monitoring purposes. Mode of transfer for these documents (fax, emails and/or post) needs to be agreed by the Sponsor according to their privacy policies. Upon notification of an AE or SAE, the trial coordinator at primary or satellite site will report SAEs to the Sponsor and follow the local procedure for documenting and reporting adverse events to the approving Human Research Ethics Committee (HREC) and local site governance office.

Roles of trial staff regarding this aspect of care need to be outlined in the site responsibility form, agreed upon by both primary and satellite sites and the Sponsor and incorporated into the contracts. Engagement with other specialists either via tele-health or onsite needs to be finalised according to the trial protocol. This is important for managing immune-related and unusual side effects of medications including trial medications.

#### *3.10.2. Additional consideration for unplanned presentation during and after hours*

In cases of presentation to hospital between medical consultations, the on-site investigator needs to be contacted by emergency staff who in turn will notify the primary site staff within 24 hours. Trial coordinators at the primary site and medical specialists are informed by any satellite staff who is the first to become aware and a joint review may be initiated using videoconferencing.

A 'trial patient alert' process would be useful for alerting the emergency staff or general practitioners that a patient is on a trial so that on-call specialists can be contacted. The name of the trial and contact details for the PI at both the primary and satellite sites needs to be included.

Patients and their families need to be educated of the need for seeking urgent medical attention and reporting to the primary and/or satellite site staff of their concerns. Patients could also be given letters or brochures for communication with clinicians in an emergency situation. Not all situations may be able to be managed at the satellite site. Inter-hospital transfers may be required in consultation between primary and satellite medical officers in some cases.

#### **3.11. Patient reported outcomes (PROs)**

**h.** The pharmacy at the receiving satellite site is contacted by telephone to notify them of the

**j.** The faxed signed copy of the Acknowledgement of Receipt from the satellite site is filed

**k.** In the event that the Acknowledgement of Receipt is not received by the primary site Pharmacy within 48 hours, the satellite site is contacted to check that the parcel has been

**3.10. Managing and reporting adverse events (AEs) and serious adverse events (SAEs)**

During planned trial consultations, the history of AEs and SAEs is obtained. Clinical trial staff needs to be aware that drug intervention studies will require minimum reporting times and the occurrence of AEs/SAEs are to be reported to the primary site in the usual within 24 hour plan by any satellite staff, medical practitioner, nurse or data manager. SAEs are managed according to the protocol and documented in the EMR or medical charts by medical specialists/medical officers at satellite sites. If EMR is not available, certified copies of the source documents may be required and sent to the primary sites for monitoring purposes. Mode of transfer for these documents (fax, emails and/or post) needs to be agreed by the Sponsor according to their privacy policies. Upon notification of an AE or SAE, the trial coordinator at primary or satellite site will report SAEs to the Sponsor and follow the local procedure for documenting and reporting adverse events to the approving Human Research Ethics

Roles of trial staff regarding this aspect of care need to be outlined in the site responsibility form, agreed upon by both primary and satellite sites and the Sponsor and incorporated into the contracts. Engagement with other specialists either via tele-health or onsite needs to be finalised according to the trial protocol. This is important for managing immune-related and

In cases of presentation to hospital between medical consultations, the on-site investigator needs to be contacted by emergency staff who in turn will notify the primary site staff within 24 hours. Trial coordinators at the primary site and medical specialists are informed by any satellite staff who is the first to become aware and a joint review may be initiated using

A 'trial patient alert' process would be useful for alerting the emergency staff or general practitioners that a patient is on a trial so that on-call specialists can be contacted. The name of the trial and contact details for the PI at both the primary and satellite sites needs to be included.

**i.** The courier service is contacted to arrange suitable pick-up/delivery.

with the original prescription in the primary site Pharmacy folder.

delivery.

170 Clinical Trials in Vulnerable Populations

received.

videoconferencing.

*3.10.1. Management at routine clinics*

Committee (HREC) and local site governance office.

unusual side effects of medications including trial medications.

*3.10.2. Additional consideration for unplanned presentation during and after hours*

Some trials will include PROs, including quality of life endpoints, usually as secondary endpoints, but sometimes as primary. It is a matter of equity that rural and remote patients have the opportunity to self-report aspects of their health and quality of life as specified in the trial protocol.

PROs are typically assessed with questionnaires, either handed out to trial participants by the research nurse or completed online. The specific questionnaires, mode(s) of administration, and timing relative to recruitment and treatment need to be followed as per trial protocols. It is also important to develop mechanisms to minimise missing data as far as possible and record reasons for missing data, so patient engagement is essential.

Many trials groups have reported success of centralised monitoring systems for maintaining high PRO completion rates. Staff should have access to ongoing training and written guidance and understand the importance of PROs.

#### **3.12. Documentation and reporting**

During trial consultations, a detailed patient history including the documentation of AEs and SAEs is obtained by doctors at primary or satellite sites or at both sites simultaneously. Results of investigations are available online at most centres. If results are not available online, the primary site will ensure certified copies are provided by the satellite site.

Physical examination may be performed by the doctor at the satellite site with or without observation by the primary site doctor and as per ICG-GCP the PI can only delegate to those with the necessary experience, training and qualifications. When joint medical consultations are conducted via tele-health, clinical encounters are documented at the site with the delegation to perform the specific study-related activity. If EMR is not available, certified copies of the source documents may be required and sent to the primary sites for monitoring purposes. Mode of transfer for these documents (fax, emails and/or post) needs to be agreed by the Sponsor according to their privacy policies.

#### **3.13. Financial considerations**

Consideration also needs to be given to how satellite sites will be reimbursed for undertaking trial specific procedures (e.g. blood tests; radiology procedures, etc.).

There are administrative efficiencies if the co-ordination of invoicing or journal transfers for trial-related expenses at satellites sites are coordinated by the primary site. Generally most of the expenses related to staff will be covered by existing work contracts and funding mechanisms that exist for routine operations. Remuneration of sites for trial-related activities should equate to the proportion of work the site undertakes and should be negotiated between Sponsor, primary and satellite sites at the outset. Primary sites need to be renumerated for coordination of trial activities and preparation of regulatory documentations across clusters.

and contractual matters are needed to reduce cost and workload, and to expedite approval

Access to Clinical Trials Closer to Home Using Tele-health

http://dx.doi.org/10.5772/intechopen.70205

173

1. Adoption of tele-trial models such as the Australasian Teletrial model as part of standard practice by cooperative trial groups, industry, researchers, governments, regulatory bod-

**3.** Development of overarching contracts for the tele-trial model between sites within clusters

**4.** Development of a pre-accreditation process where the focus is on the capability of the site and the investigator at the satellite, well ahead of any trial. Once pre-accredited, a satellite should be able to recruit to any trial immediately or at short notice, if they have a candidate case. A pre-accredited satellite could then recruit to more than one primary site, provided that the trial of interest has been approved by the primary site governance and ethical approval processes. Any primary sites could pre-accredit a number of satellite sites even

**5.** Provision of incentives by funding bodies and government and non-government organisations for hospitals, industry or trials groups to accommodate innovative models such as the Australasian Tele-trial model in their trial protocols to improve access to clinical trials

**6.** Exploration of the feasibility of adopting remote monitoring systems by Sponsors and au-

COSA acknowledges the contribution of various jurisdictions and organisations including the clinical trial groups, Medicine Australia and its industry partners, state government research offices, cancer centres and research centres in developing the Australasian Teletrial model and guide available via https://www.cosa.org.au/media/332325/cosa-teletrial-model-final-

COSA Teletrial Consortium Steering Committee, Clinical Oncology Society of Australia

**2.** Inclusion of central review processes for site-specific authorisations within clusters.

in order to simplify the contract processes at local, state and national levels.

though different sites may be part of a cluster at different times.

processes.

**4.1. Recommendations**

ies, hospitals and insurers.

for rural and regional cancer patients.

diting authorities.

**Acknowledgements**

19sep16.pdf.

**Author details**

Sabe Sabesan\* and John Zalcberg

(COSA), Sydney, Australia

\*Address all correspondence to: sabe.sabesan@health.qld.gov.au

#### **3.14. Regulatory considerations**

Many of the regulatory aspects of clinical trials are governed by local and state jurisdictions and are therefore beyond the scope of this document. It is important to engage with health service executives, ethics committees and research governance officers to expedite approval processes within clusters. However, a simplified and streamlined approach at state and national level may reduce the cost and expedite the approval processes.

It is recommended that the primary site takes the responsibility for preparation and submission of documents related to ethics, contracts and site-specific assessment forms (SSAs) in order to streamline and expedite the trial approval processes. Contractual, ethical and governance processes can be expedited when common standards and strong collaboration are established between primary and satellite sites within clusters.

It is prudent for clinicians or cancer centre managers who wish to participate in this model to get the support of their managers and chief executive officers especially in developing trial clusters between centres located within other health service districts and states so that governance and contract processes can be streamlined.

#### **3.15. Indemnity, insurance and clinical trial agreements**

Primary sites and the Sponsor assume responsibility for ensuring that criteria for safe care are met by all sites within a cluster. When undertaking investigator lead trials, both the primary and satellite are indemnified as per each state and territory health department provision. For industry-sponsored studies the indemnity is provided by the trial Sponsor (https://medicinesaustralia.com.au/policy/clinical-trials/indemity-and-compensation-guidelines/).

The Sponsor of a clinical trial takes overall responsibility for the conduct of the trial, including protocol design and the investigational product.

Agreements between sites within a cluster could be in the form of formal contracts, or overarching agreements such as Service Level Agreements (SLA). This matter needs to be solved at the local level between health services or at the state level through research and governance offices in collaboration with the Sponsors.
