“Hints and Updates”
15th February 2013
TRAINING AND SITE ACTIVATION
Video and Powerpoint presentations from the FOR DMD US Investigator Meeting (IM) are available on Chillibean. They are divided by study role (Principal (Site) Investigator, Trial Coordinator and Clinical Evaluator).
Study staff who have attended an IM (in Rochester or Newcastle) are not required to review the video but can use them as a refresher, if they think it might be useful.
As part of the study mandatory training, any study staff member who did not attend an investigator meeting is required to review the Powerpoint presentations and accompanying video(s) listed under their study role before performing any study procedure. This needs to be documented on the training form, which then should be signed by the site PI to confirm the completed training. Signed forms need to be returned to Kim Hart (via fax or email, contact details in section 2.1 of the MOO) to allow site activation.
If a primary or back-up Clinical Evaluator did not attend an Investigator Meeting, they should check with Michelle Eagle (UK/EU sites) and Wendy King (US/CAN sites) (contact details in the Clinical Evaluator Manual, section 5) to determine what type of training is required.
We have encountered some connection problems with PCs running multiple Internet Explorer (IE) sessions when logging in to EXPeRT, and also on PCs that have other browsers installed (Google Chrome and Firefox, for example). In addition to previous recommendations noted (IBM compatible PC; Internet Explorer (IE) 6 or higher; no toolbars loaded; pop-up blockers disabled), if you experience problems accessing EXPeRT through IE please try the following:
- Close other IE tabs (if any are open) and run EXPeRT alone
- If you have Google Chrome or other non-IE browsers installed (even if not actively running them) try running on a PC without these browsers installed
- If you still experience problems contact the MSG-CC help desk (FOR-DMD-Help@urmc.rochester.edu)
EXPeRT data entry
When you want to add a subject on EXPeRT, a drop-down box will ask you to enter the site country. The system will offer you only the US and UK as options (but not Canada, Italy or Germany). Please note that, regardless of where your site is located, you do NOT need to complete this field (i.e. do not need to make a selection in the drop-down box). Instead, the country will be automatically captured via the subject ID number.
In that same screen (‘add a patient’), there is a field for baseline visit date. Please note that this field does not need to be completed either, as the baseline visit date will be automatically captured on CRF01.
The physio assessment should be performed without parents present in the room. However we understand that when a child is very immature and is new to the study and staff this might be difficult. Therefore if it is not possible to gain cooperation from the child at the screening visit it is acceptable to allow the parent to stay in the room so long as they do not interfere with the assessment. On the next visit (Baseline) when the boy is more familiar with the staff, the environment and study procedures we would hope that the parent can remain outside. The requirement for this adaptation to the manual need to be determined at the discretion of the study staff on a case by case basis.
Of priority is to get a good assessment without parental influence. Please contact Michelle Eagle or Wendy King if you have any questions about this (contact details in the Clinical Evaluator Manual, section 5).
It is best to use a tripod when videoing the assessment. Do not worry about getting the perfect video. It is more important to get a good assessment. If there are two site staff available, then one person can take care of the videos leaving the evaluator to concentrate on the assessment.
FVC recording on CRFs
In order to accommodate the changes to the FVC reproducibility eligibility criterion we have modified EXPeRT to allow for capture of both FVC testing sessions at the screening visit. When filling out the paper FVC form (CRF50) please be sure to include the correct time for each testing session, which will allow us to keep track of the data later. Enter each session as a separate eCRF50 in EXPeRT. To add a second record, click the ‘+’ sign in the upper right hand corner of the screen. See page 14 of the EXPeRT User Guide v 1.3 (Adding a Record) for more information. This will allow us to document that the percent variability was calculated correctly.
Screening, randomization and study drug ordering
Screening log – CRF00
- CRF00 will be used to monitor screening at each site and must be filled out on the paper form and electronic form (eCRF)
- Paper CRF00 can be downloaded and printed from EXPeRT (from the document sharing folders in EXPeRT, lower right quadrant, under CRFs).
- On the paper form, sites can write in all the subjects who have been screened at that site as one continuous log, so they all can be seen at a glance.
- On the eCRF, however, each subject will just have their own individual one line CRF00 into which to enter the data.
- To see eCRF00 on EXPeRT, the subject has to be created first (see EXPeRT guide for details). Once the subject has been created, eCRF00 will appear automatically, together with all other screening visit forms.
Subject screening numbering
- Subjects should be numbered sequentially as they are considered for screening (pre-screened). For example, USA12S01, USA12S02, USA12S03 etc. If the subject failed screening (e.g. refused to take part in the study, failed eligibility criteria), he will nonetheless maintain this sequential screening number. Therefore the first subject randomized at the site might not be subject 01.
- Please note that if and when a subject is screened and subsequently successfully randomized the ‘S’ in position 6 of their ID will change to an ‘R’ to reflect this. The system will do that for you automatically, so you don’t need to worry about doing that yourself.
Randomization will be notified via email (see MOO, section 3.2.3, page 18).
- The randomization notification process has been configured to include the site principal investigator, primary trial coordinator, and secondary coordinators (if there are any and their inclusion has been previously requested by the site ) and the person designated as ‘study drug recipient’ into the email.
- Unfortunately, the system has now been finalized and we will therefore not be able to add any additional addresses beyond those listed above.
- Nonetheless there are some options that can be explored if you would like to add additional people to receive the notifications, such as auto-forwarding in your email system. Please contact Bill Martens (contact details provided in the MOO, section 2.1, page 8) if you need any assistance with this.
- Remember that the site investigator has to sign off on the screening visit (i.e. has to sign eCRF01) in order to randomize, and that the notifications will be generated within an hour or two of randomization. Therefore, do not complete a randomization when notifications would arrive while the site investigator or primary trial coordinator is on leave (given the speed of notification and the need for the site investigator to sign off, this is an unlikely scenario).
Study drug ordering and shipment (eCRF11)
- Date of study drug shipment to the site needs to be reported and recorded on eCRF11.
- If the study drug is shipped directly to the site investigator or to the primary trial coordinator, the recipient will be able to enter date of shipment into the eCRF11.
- For sites where study drug will be shipped to their pharmacy, they will need to agree with their pharmacy how to confirm shipment. (e.g. the pharmacy could notify the primary trial coordinator that the shipment has been received, and the coordinator can then update CRF11 in EXPeRT). Please contact Bill Martens if you have any questions about this process, including the option of having a member of pharmacy staff confirm receipt.
SCREENING VISIT AND INVESTIGATIONS
Please note that all screening study procedures should be performed only after written informed consent from the parent(s) (and assent from the child, if required) has been obtained.
The paper CRF that I am using appears as the same version but in a different format to that on EXPeRT.
Check that you are using the correct document and version number. Sometimes documents appear in an unusual order in the document list (unfortunately, we can’t control the order of documents within the folders), so check that you have scrolled down to the document that you need.
We are continuously testing the system so hopefully we will reduce the confusion around CRFs and you’ll have fewer PDFs to print out. We’ve also fixed a few other typos in some other forms so we’ll be updating all the PDF packets soon. Since minor changes may continue to happen we recommend that each time you have a visit coming up you check the document area of EXPeRT to make sure you have the most recent version of the packet you need.
Placebo tablets and packaging
At screening, the investigator should confirm the subject’s ability to swallow tablets (to comply with the study inclusion criteria). If desired, further dummy tablets can be provided to be taken home to allow the child to attempt to take the tablets in his usual environment.
Dummy tablets (the same size and appearance as the tablets that will be used in the study) will be provided by the Sponsor. Dummy tablets are packed in four-tablet wallets. The clinical trials supply company will provide up to two placebo wallets (eight tablets) per subject at each site. However, the ability to swallow tablets can be confirmed without using the eight tablets provided. For example, the subject can be asked to swallow one or two tablets in clinic and to take the remaining two/three tablets in the wallet home to practise. If the site PI has any further concerns regarding the subject’s ability to swallow tablets, further tablets can be provided in clinic at screening day 2, but this is not a requirement and will be applied on case-by-case basis, on the judgement of the site PI.
Study drug ordering – follow up visits.
The field ‘dosage held constant despite weight increase’ is only intended to be used for study drug dosage adjustments, specifically for keeping the same weight band even though the weight gain would normally have put the subject in a higher band.
The field should therefore be entered as ‘No’ unless the PI decides to maintain the same dose due to a side effect.
If a subject increases in weight from the previous visit, but does not move into the next weight band, the field should be entered as ‘No’ and the system will automatically order the correct dose
ECG and ECHO
E/E’ ratios should be calculated from the lateral walls of the LV and not from the septal.
The max septal and max posterior wall thicknesses refer to diastole measurement. Please note, whenever possible, sites should ask their ECHO department to save the ECHO images (e.g. on CD) and keep them on site for possible future reference.
Some ECHO parameters listed in the Manual of Operations, section 6.20.1, are not recordable on eCRF 73 (Tissue Doppler imaging of anterior, septal, posterior & lateral LV wall function ; Mitral annular plane systolic excursion (MAPSE) & Tricuspid annular plane systolic excursion (TAPSE)
Only abnormal finding on these parameters will need to be recorded on eCRF73 (comments); normal observations do not need to be reported.
Dietary supplements and remedies
Over-the-counter medicines, vitamins and other dietary supplements, herbal and homeopathic remedies do not represent exclusion criteria for the study.
If a subject is already taking supplements or remedies before screening, families should be encouraged to maintain the same dose and regime for the whole duration of the study. Subjects should not be encouraged to commence this treatment during the study.
If the active ingredient of the remedy is unknown, Clinicians should be the medication at least 4 weeks before screening but continuation will not preclude the subject’s participation in the study.
Screening log and screening eCRF
On the screening log, sites should record all subjects who have been considered for the study, regardless of whether or not they agree to take part, complete or fail screening, or are recruited to the study. The screening log helps us to monitor screening and recruitment rates and reasons for failure.
If a subject fails screening before consenting (e.g. refuses to attend the screening visit) only the screening log should be completed – no eCRF needs to be filled in. eCRFs need to be completed only for subjects who have provided signed consent.
Study drug destruction
Destruction of study medication (returned at each visit from subjects) can be performed at site or can be arranged via the clinical trials supply company at the site cost.
If returned study drug is destroyed at site, the study drug can be destroyed only after reconciliation at the second return of the supply (and if the counts are in agreement).
Please note , study drug accountability and reconciliation are two different steps:
- Accountability should ideally be checked by a second, independent member of study staff before discharging the study subject to verify subject’s compliance with study drug. If accountability cannot be verified in clinic, the second counting must be performed as soon as possible after the subject’s visit. If there is any discrepancy between the first and the second count, a third count will be required.
- Reconciliation can only be performed after the subject’ following visit, when the subject will returned the tablets which were handed back to be continued until new supply is delivered to the subject home.
If destruction is being performed at site, sites will need to provide the Sponsor with a certificate of destruction (as per GCP requirements). Sites must ensure that all personal identifiers are removed from the wallets (i.e. no subject names should be readable), prior to destruction of the study drug.
If sites are sending the drug to Catalent for destruction they will need to stockpile it until the end of the study to save shipping costs.
eCRFs 63 and 64 (PedsQL Core and Neuromuscular module) do not perfectly match with the paper questionnaires.
In the Parent Report for Young Children, parents have a choice of five possible answers. In the Young Child Report, children have a choice of three possible answers. For the Young Child report, you can enter the proper numeric code even though the description may not match exactly. Although all five responses show in the pull-down menu, if you try to enter one that does not apply to the Young Child version a query will appear. This discrepancy is because rather than have 10 separate data entry screens for each combination of age group and parent/child we opted to combine them into two (Core and Neuromuscular) but this means the item labels may not exactly match the paper copy you’re entering.
Since all age group versions with the exception of Toddler (2-4 years) require the collection of 2 different PedsQLs per visit (one for the child and one for a parent) you will need to create multiple records for eCRF63 and eCRF64. See the section on ‘adding a record’ in the EXPeRT user guide (available in the document sharing area of EXPeRT).