Autologous Chondrocyte Transplantation / Implantation Versus Existing treatments
PARTICIPANTS Chondral defects Why ACTIVE? Which Hospitals? Your Participation
Why do we have local study co-ordinators?
Each participating site will recruit a study co-ordinator to help enter patients into the trial and to ensure things run smoothly. This position is suitable for someone such as a nurse or physiotherapist who is already working with the patient group to be studied and has had previous research experience (or is willing to undertake training). The hours of work will depend on the number of patients to be recruited into the trial at your site, but is unlikely to exceed a few hours each week and the job will continue throughout the two-three year recruitment period. You will receive training centrally from the Trial Manager. These notes are designed to provide further training and support to you and can be downloaded here.
Most hospitals have already recruited a co-ordinator. Co-ordinators' names can be viewed along with the other local ACTIVE team members on the Which hospitals? page.
What does a local study co-ordinator do?
Please click on the bullet points below for guidance on what to do. It is important that you follow the correct protocol for entering patients into the trial as summarised in the trial schema and flow diagram. You should also familiarise yourself with the Patient Information Leaflet.
1.1. The surgeon is initially responsible for identifying suitable patients and giving out the Patient Information Leaflet. If a patient is interested and signs the pre-consent form, the surgeon will pass the patient’s details on to you by completing Parts A & B of the Patient Entry Form.
1.2. You check Parts A & B of the Patient Entry Form are complete and check the patient meets the eligibility criteria.
1.3. You arrange an appointment
for the patient to visit you within 3months prior to his/her expected
(b) Check the patient has read and understood the patient information leaflet and is happy to enter the trial knowing there is a 50/50 chance of being randomised for ACT or one of the alternative treatments (which the surgeon will have already discussed with the patient).
(c) Ensure the patient is aware that they will be expected to complete a pack of 4-5 questionnaires each time they see the Independent Assessor, and complete the same questionnaires annually through the post. Also mention that they will be expected to remain contactable by notifying research staff if their address/telephone number changes.
(d) Test the patient’s knowledge by asking questions. Repeat information from the Patient Information Leaflet to clarify anything when necessary. You may also refer to the Rehabilitation Advice Leaflets for information from Physiotherapy about the surgical procedures, and rehabilitation.
(e) Give the patient an opportunity to speak to the surgeon again before deciding to participate.
(f) If the patient decides to participate you both sign three copies of the consent form - 1 copy to go in the patient's notes, 1 copy to be given to the patient, and 1 copy for you to file securely. Please also send a photocopy of the consent form (using the top copy so that it photocopy's clearly) to the Trial Office.
2.1. If you are using a commercial cell supplier it’s no longer necessary to carry out the blood tests before randomisation. Under the Human Tissue Authority regulations the blood is tested at the time of the biopsy (first stage AC/MACI) and this is organised by the company. Therefore you may randomise your patient without the blood results unless the surgeon requests the results of the blood test before entering the patient into the trial.
3. Contact the central randomisation service (by telephone or internet) to randomise patients, co-ordinate with the Independent Assessor and schedule the allocated treatment
3.1. Before contacting the central randomisation service you will need to have completed the Patient Entry Form (which should confirm the patient is eligible) and obtain a copy of the patient’s completed Lysholm questionnaire from the Independent Assessor’s pre-randomisation assessment.
3.2. You should arrange for the Independent Assessor to carry out the pre-randomisation assessment within 3 months prior to surgery. This assessment should, whenever possible, coincide with the patient’s normal pre-operative clinic appointment. You will therefore need to let the Independent Assessor know when the patient’s pre-operative clinic appointment is (there will probably be an Appointments Clerk you can ask).
3.3. If you randomise on the same day the patient visits for their pre-randomisation assessment you can then inform the patient, in person, of their allocated treatment.
3.4. To randomise patients, go to https://www.trials.bham.ac.uk/active (you will be trained in using the online system and have a password) or or phone up Birmingham Clinical Trials Unit (BCTU) on 0800 953 0274 (+44 (0) 121 687 2319 outside UK). BCTU may also ask you to fax them the Patient Entry Form and the pre-randomisation Patient Lysholm form on 44(0) 1216872313.
3.5. It is recognised that certain centres may have difficulty in managing their caseloads with the uncertainty of whether a patient will be requiring ACT or a shorter standard operation. To ease difficulties of resource allocation there is the option of pairwise randomisation. Pairwise randomisation means you randomise two patients simultaneously in the knowledge that one will receive ACT and the other will not. The randomisation centre will only allow this method of randomisation if both patients really are randomised simultaneously. Therefore, you must have the pre-randomisation Lysholm scores and a completed Patient Entry Form for each patient ready at the same time.
3.6. Once the patient is randomised you must inform the theatre manager of what treatment has been allocated and confirm the date of surgery.
should also inform the patient’s GP using the GP
letter or check whether the surgeon will inform the GP.
4.1. Since the aim of a clinical trial is to compare the effects of different treatments it is important to minimise sources of bias between different treatment groups or ‘arms’ of a trial. For example, patients may have to wait longer for ACT than for a standard surgical procedure, and this difference in waiting times between the two arms could cause differences in patients’ outcome scores, making it difficult to identify any ‘real’ differences between ACT and the standard treatment. To minimise this type of bias, patients’ treatment should be completed as soon as possible after randomisation and in any case within 3 months of randomisation.
4.2. Another method used in
this trial to reduce possible sources of bias between study arms is stratified
randomisation to ensure each arm has a similar spread of patient/clinical
characteristics. The stratification variables for ACTIVE are:
5.1. The Independent Assessor is the only member of the local research team who is blinded to patients’ treatment allocation and it is very important that you avoid him/her becoming ‘unblinded’. If the Independent Assessor knows what type of treatment a patient had, this can introduce bias into his/her outcome assessments, e.g. if the Independent Assessor forms an opinion on what type of treatment is working better, and knows which patients had that treatment, he/she may unwittingly score those patients better.
5.2. It is very easy in a busy clinic or ward to overhear staff discussing patients’ treatment, or to access patients’ notes. Therefore, to maximise blinding, the Independent Assessor (probably a Physiotherapist) will not be involved in the treatment of trial patients and will, if possible, not visit any clinics or wards when the trial patients are there.
5.3. Ideally, the Independent Assessor will assess patients in a separate part of the hospital, although part of the assessment may involve using the physiotherapy gym. As co-ordinator you will need to liaise with the Independent Assessor so you should be particularly careful not to discuss the trial patients’ treatment, or say anything which could give a clue to which treatment the patient had.
6.1. As mentioned above, you will need to ensure the Patient Entry Form is complete before randomising patients. This form will be explained in your training session. When the surgeon passes the Patient Entry Form to you please check he has filled in parts A & B. Any missing information from Part A can be found from the patient’s notes or by electronic patient records such as PAS. If a hospital sticker has been used for Part A please check the patient’s telephone number is also included on the form. If any information is missing from Part B you will need to ask the surgeon to complete it. For example, the surgeon needs to give an estimate of the predicted size of defect even if this information isn’t clear from the patient’s notes.
6.2. You should keep a copy of the Patient Entry Form filed securely and put a copy in the patient’s notes to show which treatment the patient has been allocated to receive.
6.3. You will be advised on how to enter the information from the Patient Entry Form into the database.
6.4. After the patient has had the trial treatment please check the surgeon sends you a completed copy of the Treatment Record Form. The Treatment Record Form must include the date of treatment (or if ACI/MACI, dates of both stages) as this information will enable the Trial Manager to forecast when the post-operative assessments should take place. Please send a copy of the Treatment Record to the ACTIVE Trial Office.
7. Liaise with other members of the research team as necessary to assist in the smooth running of the trial
7.1. At the beginning it is important that you liaise with your Principal Investigator or any surgeons that might recruit and treat trial patients, to check they are aware of the randomisation process and can forward the Patient Entry forms to you. You should liaise with the Independent Assessor to ensure she/he books patients for their pre-randomisation assessment on an appropriate date, within 3 months prior to surgery, coinciding whenever possible with the patient’s pre-operative clinic appointment. You may also need to liaise with the Theatre Manager to book theatre slots once you have randomised patients and know their allocated treatment. You may want to set up a meeting between staff members involved in the trial at your hospital to discuss how things will run. Please contact the Trial Manager for any information you may wish to present at a meeting.
8.1. Please contact the Trial Manager, Dr Johanna Wales by email/telephone (firstname.lastname@example.org tel: 01691 404142) to discuss any problems with recruitment or issues relating to the trial.
Once a patient has been entered into the trial and treated it’s very important you send copies of the following to the Trial Office:
What if the patient wants to sign up for the trial straight away and avoid making a separate return visit to see the co-ordinator?
To comply with ethical guidelines, patients must have had the Patient Information Leaflet for at least 24 hours before they give written consent to participate in the trial. Even if patients have read the leaflet and talked it over with relatives, they should still ‘sleep on it’ before making a final decision and giving informed written consent.
Normally patients will first hear about the trial when they see the consultant in the outpatient clinic. However, if the surgeon can identify possible candidates for the trial and send them a Patient Information Leaflet before they are seen in clinic, and provided the patient is likely to get treated within 6 months after their clinic appointment, you could arrange to see patients for informed consent and a blood test on the same day the patient comes to hospital for their outpatient clinic appointment.
Can we offer trial patients travel expenses?
Unfortunately travel expenses cannot be offered to trial patients when they visit you for informed consent and a blood test. However, trial patients can claim travel expenses for attending the assessments which cannot coincide with routine visits to the hospital, i.e. the 6-month, 3-year, 5-year, and 10-year post-operative assessments, provided they present their travel details or receipts to you or the independent assessor. MRC funding will pay on the basis of reasonable actual expenditure incurred, up to £25 per visit or in special circumstances more at the discretion of the Trial Manager.
What if the patient decides not to participate?
The patient is under no obligation to participate in the trial. If the patient decides not to participate, you should record the reason (if given) on the Patient Entry Form. Patients must not be coerced into participating, but if they are undecided, you should provide enough information to ensure the patient is able to make a fully informed decision.
be excluded if they don’t get their randomised treatment?
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ACTIVE is being carried out by the Robert Jones & Agnes Hunt Orthopaedic & District Hospital NHS Trust in collaboration with the University of Birmingham Clinical Trials Unit and Health Economics Facility. The trial is funded by the Medical Research Council and administrated by Keele University.