The Site Initiation Visit (SIV) is required to prepare and set up a research site to conduct a study and must occur prior to patient recruitment. 

The principal investigator (PI) must attend this visit together with as many members of the research team as possible. Representatives from any supporting departments should also attend where possible e.g. pharmacy, radiology, laboratories.

If NBT have agreed to sponsor your study, they are required to attend the SIV. Please provide the Research & Innovation Office advance notice of the date for the SIV to ensure attendance.

The role of this meeting is to discuss the protocol, especially the inclusion/exclusion criteria, study procedures, and the research participant pathway the sponsor will discuss the monitoring plan for the study – including safety reporting procedures and monitoring to Good Clinical Practice (GCP) and International Conference on Harmonisation (ICH) requirements.

When conducting the site initiation visit (SIV):

• Review the protocol in detail
• Review instruction on any specialised procedures such as diagnostic tests and special computer programs
• Receive direction for Case Report Form (CRF)/electronic CRF completion & safety reporting
• Define source documents
• Be prepared to provide sponsor with an update on any study related
• Issues
• Document all study related training
• Review the Investigator Site File 

All documentation generated before, during and after undertaking a research project must be kept together in an Investigator Site File. It is important that such documentation is complete, legible and easily accessible at any time for monitoring and or audit purposes.

For every research study it is important to keep clear accurate version controls of all trial related documents including; Protocol, Patient Information Sheet (PIS), consent, GP letter, trial specific procedures and Standard Operating Procedures (SOPs). The current approved versions of all study documents must be filed in the Investigator Site File. All previous versions must also be retained in the Investigator Site File clearly marked as superseded (with details of current approved version number and date, initialled and dated.

The study documentation also serves some other important purposes:

• To demonstrate the compliance of the investigator, sponsor and monitor in accordance with Good Clinical Practice (GCP)and International Conference on Harmonisation (ICH) guidelines and any regulatory requirements
• Assist all parties in the successful and smooth management of the research;
• Provide monitors/auditors with the necessary information they need to confirm the validity of the research, its conduct and the integrity of the data collected

If NBT is the sponsor, then we can provide the Investigator Site File and index pages. To request this, please contact us via research@nbt.nhs.uk.

If you are the Lead Site of a multi-centre study, sponsored by NBT, we will also provide you with Master Trial Files with index pages – it will be important to clearly label the volumes of these files with appropriate indexes.  These files will contain all documentation relating to the research study and to all the recruitment sites involved in the conduct of the study. As a Lead Site, you must provide an Investigator Site File for each recruiting site.

The Investigator Site File will contain only documentation relating to the local recruiting site i.e. participant consent forms (which should be protected by envelopes to maintain confidentiality) and local screening and recruitment logs. Where you are a Lead Site and a recruiting site, there may be duplication of some documents, but this is required to maintain a clear documentation trail for monitoring and audit purposes. In this situation, please note that the duties on the local delegation log may differ from that on the delegation log in the Master Trial Files.

In line with GCP & ICH guidelines, the Investigator Site File and Master Trial Files (where applicable) must be kept in a secure locked room as some of the contents will contain patient related data and must be kept confidential.

The permissions or approvals required will depend on the type of research you are undertaking.

Permissions may include:

• NHS R&D approval
• NHS Research Ethics Committee
• NIHR Portfolio Adoption
• Medicines and Healthcare Products Regulatory Authority (MHRA)

For general information on all of the above permissions see: http://www.nres.nhs.uk/applications/approval-requirement

Integrated Research System (IRAS)

Most applications can be made via the (IRAS)  http://www.myresearchproject.org.uk.

IRAS was developed to bring all the research regulatory application forms together in one place.  By completing a checklist of questions, the system will generate the forms you need to complete based upon your responses including the:.

• Portfolio Adoption Form (PAF)
• Research & Development (R & D) Form
• Site Specific Information (SSI) Form

An IRAS training module is available (approx 60 minutes) that will lead you through the system and show you how all of the forms are generated.  It also explains how certain information is pre-populated throughout the form to save having to repeat certain text.

NIHR Portfolio Adoption

All researchers with funded research projects should be encouraged to apply for NIHR portfolio adoption.  This is important in order to bring additional funding into the Trust to support the delivery of research.

On the first page of their IRAS application you can choose to have your project assessed for NIHR Clinical Research Network (CRN) support and inclusion in the NIHR Clinical Research Network (CRN) Portfolio. 

Research studies funded by NIHR and NIHR partners are eligible to be adopted on to the NIHR Portfolio. Other criteria for adoption include who is funding the research, if funding is awarded in open competition, if the study has received a peer review and if the research is of value to the NHS and fits within the needs and realities of the NHS.  A portfolio adoption form (PAF) should be completed and submitted via IRAS. One application is required for the entire research project from the lead site, where the Chief Investigator is based. For more information visit:http://www.crncc.nihr.ac.uk/about_us/processes/portfolio/p_how

If your research study meets the criteria for portfolio adoption, it is important to submit the PAF form at an early stage (prior to the R & D form & SSI form) in order to be processed via the ‘Coordinated System for gaining NHS Permission’ (CSP) system for R&D approval, and funding received from the NIHR.

During the sponsorship review NBT may recommend that your research is submitted for NIHR Portfolio adoption. 

• Strong links with the Musculoskeletal Research Unit at Southmead Hospital Bristol (part of the School of Clinical Sciences, University of Bristol)
• Our research interests at the Musculoskeletal Research Unit at Southmead Hosptial Bristol include bone density and fractures in children, osteoporosis and vertebral fractures in older people, high bone mass, hypermobility, scoliosis and the genetics of bone development.
• We support and participate in multicentre clinical observational and interventional studies in rheumatoid arthritis, inflammatory myositis, systemic sclerosis, psoriatic arthritis and ankylosing spondylitis.
• North Bristol Trust Rheumatology department is part of several UK/European networks (the Early Rheumatoid Arthritis Network (ERAN), BIAS, TRACE, TCL and (genetic predictors of response to anti-TNF) with collaborations with:
  • University of the West of England (UWE)
  • University Hospitals Bristol Foundation Trust
  • Royal National Hospital for Rheumatic Diseases in Bath
  • University of Oxford
  • University of Nottingham

• North Bristol NHS Trust hosts an Academy within the University of Bristol Medical School. In rheumatology we help deliver the musculoskeletal element of the Musculoskeletal Diseases, Emergency Medicine and Ophthalmology (MDEMO) course. We host 3rd year medical students for 9 weeks in four blocks throughout the year.
• We organise and run teaching and training sessions for junior doctors at North Bristol NHS trust and rheumatology trainees from across the Severn Deanery region. In addition we run teaching sessions for doctors taking their postgraduate examination.

The role of the Neuro-Oncology Clinical Nurse Specialist (CNS) focuses on providing support, information and advice to patients and relatives with a diagnosis of a malignant primary brain tumour.  Currently there are two Specialist Nurses within the team and a Support Worker. We work closely with both the Neurosurgeons at Southmead and the Oncologists at the Bristol Oncology Centre.

We primarily support patients who live within the Bristol, North Somerset and Somerset region. For patients outside of these areas we handover to the local specialist team to take over and continue support locally.

The Neuro-Oncology Specialist Nurse Team at Southmead Hospital can be contacted on 0117 414 7352. This will be answered by one of the team between the hours of 08:30 to 15:30 hrs Monday to Friday.

We do not work on Weekends or Bank Holidays.

Outside of these hours there will be an answering machine on this number and any messages left on this answer machine, will be picked up on the next working day, except on Bank Holidays. 

This service is not for emergencies and patients / carers should contact the nearest A&E or local GP or in case of a medical emergency dial 999.

Radiation

The majority of high-grade gliomas (WHO grade 3 and 4) require radiotherapy following surgery. Although radiotherapy rarely cures glioblastoma, studies show that it doubles the median survival of patients, compared to supportive care alone. A recent important study (known as the 'Stupp' trial) showed a benefit for chemotherapy using temozolomide in patients with glioblastoma multiforme. In the study, the median survival of patients who received temozolomide in addition to radiotherapy was increased by 2.5 months and two-year survival by 16 percent. For grade 3 gliomas the options for treatment following surgery would involve radiotherapy alone or chemotherapy alone followed by surveillance (i.e. keeping an eye with regular scans). Following surgery to obtain tissue for biopsy or to resect a grade 4 glioma (or glioblastoma), the patient is scored on their general well being (WHO performance status) and those with performance status of 0 or 1 are offered high dose radiotherapy treatment along with Temozolomide tablets during the treatment.

Further details about radiotherapy can be obtained by viewing this booklet which has been designed specifically for patients treated at the University Hospitals Bristol NHS Foundation trust:

Chemotherapy

Chemotherapy is an integral part of the treatment of Cancer and the decision on when to use it is dependant again on the type of tumour, but also on the clinical status of the patient (i.e. how well is the patient and will he/she be able to tolerate the treatment). For grade I gliomas no chemotherapy is currently indicated. For grade 2 gliomas, the role of chemotherapy is limited and is currently restricted to clinical trials. For grade 3 gliomas (Astrocytomas, Oligo-astrocytomas amd Oligodendrogliomas) the options for treatment include either initial radiotherapy followed by chemotherapy with either Temozolomide or PCV (Procarbazine, CCNU and Vincristine). The exact management plan is arrived at after the Clinical Oncologist is able to have a full and complete discussion with the patient and family about the pros and cons of each treatment. For grade 4 gliomas, following surgical resection of the tumour where appropriate, a decision about additional treatment is made by the Clinical Oncologist depending on the general fitness level of the patient (see links to WHO performance status above). The current standard of treatment in a fit patient would be Radiotherapy to the tumour bed and concomitant administration of Temozolomide (i.e. Temozolomide taken orally during the administration of Radiotherapy) followed by a few cycles of adjuvant Temozolomide orally over a period of time. Additional information about Temozolomide can be found here:

Awake Craniotomy

This is a highly specialised procedure performed when tumours are present very close to areas of the brain that control movement, speech and language, to minimise injury to these areas and preserve function. An important part of the brain, which controls voluntary movement of the opposite side of the arm, leg, face and tongue, is called the motor cortex. (See fig below)

The anatomical region of the brain known as Area 4 (coloured red in the figure above) was given the name primary motor cortex after the Canadian Neurosurgeon Dr Wilder Penfield showed that focal stimulations in this region elicited highly localized muscle contractions at various locations in the body. The motor cortex also includes Area 6, which lies in front of Area 4 and is divided into the premotor area (or premotor cortex) and the supplementary motor area. The premotor cortex is believed to help regulate posture by dictating an optimal position to the motor cortex for any given movement. The supplementary motor area, for its part, seems to influence the planning and initiation of movements on the basis of past experience. The mere anticipation of a movement triggers neural transmissions in the supplementary motor area. Tumours in the Premotor and supplementary motor areas can be removed in most instances without any significant loss of function to the patient, though there may be some temporary weakness on the opposite side of the body if these areas are removed on the dominant side (i.e. in the majority of people (both right and left handed) the left half of the brain is dominant). However tumours in the primary motor cortex are difficult to remove without loss of function of the opposite side of the body. Any injury to the primary motor cortex is in most instances likely to lead to irreversible loss of function of the arm, hand , leg or face of the other side of the body.

If a glioma is present very close to the primary motor cortex then an 'Awake craniotomy' can be performed to minimise injury to this area. In this procedure the patient is awake (but pain free) during parts of the operation to remove the tumour. The surgeon and his team are able to talk to the patient while the operation is in progress. The surgeon stimulates various areas of the brain and looks for muscle contractions in the patient and sometimes correlates with electrical recordings obtained from specific muscle groups in the arm and leg. The patient is also asked to move the arm, hand, and leg repeatedly to observe for any decrease or loss of function while removal of the tumour is underway. In this way the surgeon is able to obtain a map of the opposite side of the body on the brain surface and is able to avoid injury to areas of the brain that he/she knows is responsible for movement. This is known as 'Cortical mapping'. This procedure is also performed when tumours that are very close to the speech / language areas of the brain have to be removed. In this case the patient is asked to repeat a variety of small simple tests (like naming objects, counting numbers etc) while the operation is underway to help prevent any injury to the speech & language areas of the brain. The risk of developing a neurological disability like weakness of arm / leg or difficulty in speech can be significantly reduced by performing this procedure where appropriate, but the risk can never be completely eliminated.

Gliadel

Carefully selected patients with a suspected malignant glioma on an MRI scan may be eligible for application of Gliadel wafers in the tumour cavity at the time of surgery to resect the tumour. A team of experts at the Multi disciplinary meeting will make the decision about the suitability for this treatment. If the patient is assessed and found suitable for this treatment then the Neurosurgeon will discuss this in detail with the patient and family at the initial consultation. Gliadel is a form of topical chemotherapy containing the drug called Carmustine (or BCNU), which has shown some benefit in clinical trials. NICE has approved this treatment in selected cases of newly diagnosed malignant glioma. 

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