Facilities & Expertise

Equipment | Pharmacy Support | Special Techniques | Participants | Regulatory | Research Ethics

Equipment

Full support and equipment is available for studies that require intensive subject monitoring. In addition to executing studies ourselves, the PARC Unit can also be made available to other local investigators planning to undertake specialised studies.

• Cardiovascular monitors with ECG, oxygen saturation, non invasive blood pressure
• ECG and non-invasive cardiac output monitoring (NICOM device)
• Resuscitation trolley with defibrillator
• Infusion pumps/syringe drivers
• Emergency management through the 24 hour on-call medical team at the hospital
• Centrifuge, freezers, etc.

Pharmacy Support for research studies

Comprehensive research pharmacy capabilities including compounding and manufacture

• Sterile IV, SC, i.d drug supply
• Drug dispensing accountability etc
• Randomisation
• Schedule 8 drug storage and supply
• Encapsulation and placebo formulation

Special techniques

Pain models

In CNS Pharmacology it is usual to incorporate several biomarkers or models in one panel to plan a comprehensive understanding of drug action. Pain models are useful for:

• Screening for analgesic drug action
• Examining dose-concentration high response relationships (PK/PD modelling)
• Dose duration responses
• Efficacy of drug combinations

Pain models in PARC include:

• Cold pain model
  This is a nociceptive model with excellent sensitivity to detect opioid drug action and opioid-related hyperalgesia. The test involves immersion of a forearm into warm water, then under ischaemic conditions immersed into a controlled temperature stirred bath at 2 C. Time to pain detection and pain tolerance are recorded. Sample data are shown.
• Electrical pain
  This is another nociceptive model which can be used as a type of 'internal standard' as it does not show opioid related hyperalgesia.
• Pressure thresholds
  These are measured at the thenar eminence at a controlled rate of increase. The output is measured in Newtons.
• Ischaemic pain
  Time to pain detection and pain tolerance are measured when the forearm is exercised at a controlled rate under ischaemic conditions
• Intradermal capsaicin
  This is a model of neuropathic pain. We use intradermal injection rather than topical application because of its better spatial resolution. Response includes local pain, flare, hyperalgesia to punctate stimuli (von Frey hairs) and mechanical allodynia measured with a foam paint brush. We have developed a sterile multi-use capsaicin formulation for use in such studies. Intradermal capsaicin will detect the effects of single doses of drugs with anti-neuropathic pain activity, eg. gabapentin or pregabalin.
• Specialised temperature bars
  This is a test of participants response to temperature. Evidence suggests that temperature sensitivity is dysfunctional in people with chronic pain. Therefore investigating response to temperature in chronic pain patients may provide additional information to better understand what causes chronic pain to occur in some people. Participants are required to place the body region of interest (e.g. palm, leg etc.) onto the temperature bars for a specified duration of time. Both affected and unaffected body regions can be investigated to compare temperature sensitivity between painful and non-painful body regions. Once participants remove their body region from the specialised temperature bars, participants are asked to fill in various visual analogue scales rating the sensation experienced. There is no risk of scarring or permanent change in skin sensitivity after exposure to the temperature bars.

Other measures of CNS drug effect

• Computerised pupillometry
  We use the AMTECH computerised infrared pupillometer for accurate pupil measurement. This is principally used for the assessment of CNS action of opioids.
• Saccadic eye movements
  Measuring the peak saccadic velocity is a non-invasive objective measure of sedation with extensive literature to support its use. It has a wider dynamic range than pupillometry for measurement of CNS effects.
• Measurement of pyschological effects of opioids and related drugs
  We use a variety of pen and paper scales to assess subjective drug effects including bond and lader visual analogue scales, MBG scales of ARCI scores etc.
• EEG

Participant Population

We have a database of healthy volunteers to assist in recruitment to pharmacokinetic and pharmacodynamic studies. We have successfully and safely recruited healthy volunteers for a study of epidural anaesthesia of a depot local preparation.

We generally invite patient participation in our trials by direct advertising and liaising with the local media. For patients of unusual types we liaise with local physicians for referral. Patient populations we have successfully recruited include:

• Painful diabetic neuropathy
• Sciatica
• Complex regional pain syndrome
• Opioid-related hyperalgesia
• Patients participating in an opioid maintenance program
• Medication over-use headache
• Migraine
• Opioid induced constipation
• Chronic tension type headache
• Post-herpetic neuralgia
• Opioid and non opioid related endocrine dysfunction

We have successfully completed studies at a single centre where the sponsor had been advised they would need to go to a muticenter approach for satisfactory recruitment. We are able to assess the feasibility of other populations.

Regulatory Review

Australia has one of the most favourable regulatory environments for clinical research. The dominant method of approval of studies is that the Ethics Committee accepts the responsibility of regulation. Following regulatory approval, a single page notification system is sent to the Australian regulator (Therapeutic Goods Administration). No regulatory review is done nor is there any waiting period. Alternatively the sponsors or Ethics Committee may choose to request regulatory review; however, this is rarely the path chosen. Details of the Australian regulatory system for clinical trials is found on the TGA website.  

Research Ethics Committee Approval

As would be expected in the environment where the regulatory authority effectively provides the regulatory function, the Research Ethics Committee of the Royal Adelaide Hospital is scientifically and procedurally thorough. A single submission is made; but it is firstly reviewed by a technical review committee, the Investigational Drugs Sub-Committee (IDSC) and subsequently (1 week later) by the Research Ethics Committee (REC) which performs a more general ethics review. There is a three week lead time for submission to the IDSC. Any queries from the IDSC or REC are handled rapidly on an ongoing basis without needing to wait for subsequent meetings.

Currently, the RAH REC is undertaking administrative changes to its service and will incorporate research governance requirements. Applications will be completed online using a centralised approach. Please refer to the RAH REC website for the most up-to-date information.