Frequently Asked Questions

Questions (full Q&A details follow this section)

• What is the definition of a clinical trial?
• What documents should be included in a pharmacy file?
• What are the licensing requirements of a clinical trial?
• What are the labelling requirements of a clinical trial?
• What areas of service do pharmacy charge for when participating in clinical trials?
• What are the various phases of a clinical trial?
• What is the new model Clinical Trial Agreement and what does it mean for pharmacy?
• When do I need a QP (IMP) release statement?

Q. What is the definition of a clinical trial?

A. A clinical trial is an investigation by a doctor or dentist involving administration of a medicinal product in patient and non-patient volunteers, to discover the effects and/or adverse reactions of the product.

Q. What documents should be included in a pharmacy file?

A. A typical pharmacy file for both company and investigator-led studies should consist of the following documents:

• Protocol and any amendments
• Regulatory and ethics approval documents
• Latest version of Investigators brochure (usually company-led studies only)
• Copy of Patient Information Leaflet
• Drug accountability logs
• Prescription forms (must include a sample)
• Receipt and return of study medication forms
• Code break envelopes and procedure
• Temperature Log
• Signature Log
• CVs
• Financial and confidentiality agreements
• Correspondences  

For further information please refer to 'SOPs and Checklists for Pharmacy Personnel: an aid to producing Pharmacy Clinical Trial Standard Operating Procedures'. This booklet is produced by The Institute of Clinical Research and can be ordered via the ICR's publication page.

Q. What are the labelling requirements of a clinical trial?

A. Double blind studies should be labelled the same, and supplied in child-proof containers.

The 'Global' requirements for labelling of such materials are covered by the EEC directive 65/55, and should include the following information:

•  Contents and dosage form

• Treatment/drug name or code
• Other pharmacologically active ingredients
• Strength
• Patient number
• Visit reference
• Method and route of administration
• Dosage instructions
• Warnings
• Storage conditions
• If necessary, special destruction instructions
• Batch number
• Expiry date
• Sponsors name and address
• Name of investigator

EXAMPLE:
'FOR CLINICAL TRIAL USE ONLY - KEEP OUT OF REACH OF CHILDREN'

FOR CLINICALTRIAL USE ONLY
Patient number: 1001Run-In medication
(15) Drug x 25mg capsules or Placebo

Take ONE capsule EACH MORNING, with food

Expiry date: XX/XX/XXXX Batch number: XXX
Store in a refrigerator
Sponsors: XXXXXX
Investigator: XXXXXX
KEEP OUT OF THE REACH OF CHILDREN

It is good practice to use at least seven point text or larger. Unfortunately this may cause a problem with smaller packs.

Reference: CRfocus Volume 12 Number 3 May 2001
13 'Manufacture of investigational medicinal products'
Guide to Good Manufacturing Practice for medicinal products.

Q. What areas of service do pharmacy charge for when participating in clinical trials?

A. This list is an overview. For further information please refer to the 'Pharmacy Fees Survey' prepared by the Institute of Clinical Research Pharmacy Sub-Committee, of which, hard copies are available on request from info@icr-global.org

• Set-fee for an initial study:
• Set-up fee for an extension study
• Aseptic set-up fee
• Extemporaneous preparation set-up fee
• Dispensing fee
• Dispensing fee which requires IVRS
• Controlled Drug dispensing fee
• Aseptic dispensing fee
• Extemporaneous dispensing fee
• Storage Fee for: Room temperature storage / Fridge/Freezer storage / Controlled drug storage
• Destruction fee
• Prescription charges (please refer to the Department of Health - Prescription charges for drugs given to outpatients in clinical trials document)

Q. What are the various phases of a clinical trial?

• A. In-Vivo studies
  Live animal studies provide toxicology data about a prospective drug (acute, chronic, reproductive toxicity, and carcinogenesis studies), pharmacokinetic studies and pharmacodynamic studies
  It is vital that the drug is shown to be safe in this phase, as in the next phase, the drug will be administered to humans.
  

• Phase I (50-100 patients)
  These studies are carried out on healthy volunteers (except for example cancer chemotherapy studies usually use patients rather than volunteers since these drugs often have fairly high toxicity).
  The primary objective is to gather safety data, defining a dose that might be effective, investigate the absorption in a pharmacokinetic aspect, pharmacokinetics and pharmacodynamic profile and drug interactions.
  If the results of the Phase I study show that there are no contra-indications to administering to patients the study will proceed to Phase II.
  
• Phase II or 'Therapeutic Pilot Studies' (100-200 patients)
  The drug is administered to patients suffering with the disease in question. This phase is usually performed as a double-blind, randomised, placebo controlled study usually carried out in a hospital or a laboratory.
  The primary objective is essentially to demonstrate the pharmacological activity and to assess short-term safety in patients suffering from the target indication.
  This phase also aims to provide a determination of appropriate dose regimens and dose response relationships.
  
  Throughout this study the programme will identify 'milestones' or 'key targets', at which point decisions will be made. The decision will be whether or not to continue the programme into Phase III.
  
• Phase III (500-5,000 patients)
  
  Phase III studies are large studies that may investigate the effects of the drug on thousands of patients.
  The main aim of this phase is to investigate the safety and potency of the new drug. The big sample size means that the majority of the possible adverse effects of the drug will be seen, but above all the most important factor is that the drug is shown to be acceptably safe.
  This phase would normally be conducted as a randomised, double blind study, but unlike Phase II they will usually compare the new drug with a previous drug of choice for the disease in question rather than a placebo.
  If the study is successful a licence can be applied for.
  
• Phase IV (Post-Marketing Surveillance)
  Phase IV studies are usually performed after approval of a drug for a product licence.
  The aim of this phase is to provide further information about the efficacy and toxicity of the new treatment.
  Once a new drug is marketed and for a period afterwards, it is the doctor's responsibility to report any side effects that occur in patients. This is done via the yellow form found at the back of the BNF.
  Reference:Student BMJ volume 9 February 2001

Q. What is the new model Clinical Trial Agreement and what does it mean for pharmacy?

A.The model Clinical Trial Agreement has been written as a response to the Pharmaceutical Industry Competitive Task Force's (PICTF) investigation into the international competitiveness of the pharmaceutical industry in the area of clinical trials conducted in the UK. It found that a number of factors were resulting in unnecessary delays in the implementation of studies at NHS sites and as a result the agreement was written. The agreement lays out contractual principles for clinical trials that both the ABPI and the DoH believe to be acceptable. All drug studies sponsored by commercial companies, conducted in NHS establishments, may be done under this model agreement. Exclusions include healthy volunteer studies and those conducted in primary care (a separate agreement is applicable). The use of this model agreement is entirely voluntary and NHS Trusts may continue to use their own.

The main aspect that affects pharmacy is that there must only be one agreement. That is the Trust will enter into the agreement and not individual departments within the Trust. The pharmacy fees will have to be incorporated into the agreement along with other costs. A practical solution is to add the Pharmacy fees in Appendix 5 to the main agreement. The actual scale of fees is set according to the actual requirements of the study using a pre-agreed scale of fees for pharmacy services. This new model agreement does not set out to dictate the level of fees.

It is clear from the above, that to ensure progress of a satisfactory Clinical Trials Agreement and the implementation of studies at NHS sites, that there is a good working relationship between Principal Investigators, support staff (including pharmacy) and the Trust's Research and Development Managers.

Q. When do I need a QP(IMP) release statement? 

A.Under the EU Directive and Medicines for Human Use (Clinical Trial) Regulations all IMPs (test drug, placebos and comparators) must be manufactured according to GMP and released by a QP.

The QP must certify that each batch complies with: GMP, regulatory approval and the product specification file. The QP release statement therefore is the final release of the batch and contains the following, or similar, wording: “this batch of product has been manufactured in full compliance with EU-GMP requirements and the Clinical Trial Authorisation”.

The trial sponsor must ensure that there is QP release for each batch of IMP.

• For commercial studies the pharmaceutical company sponsoring the trial will have the appropriate documentation and it is not necessary for individual sites to have copies of the QP release statement.
• For multicentre non-commercial studies the trial sponsor may be a Trust, University or research organisation (eg CRUK, CCLG) and they should hold the QP(IMP) release documents. However, in these cases it may be prudent for the site pharmacies to request the QP release statements for the IMPs, especially when they have been sourced from outside the UK or EU or from a little known manufacturer, in order to satisfy themselves that the IMPs are of a suitable quality and fit for purpose.
• If the study is an investigator-initiated single-centre study it is essential that the pharmacy is involved in the specification and sourcing of the IMPs  and has a copy of the QP(IMP) release documents