1. Newsletter
Issue 3
April 2014
DearInvestigatorsinthe CERTiFystudy
Welcome to the third issue of the CERTiFy newsletter. With this newsletter we would like to
inform you about the current progress of the study.
Study progress and recruitment:
Twelvesites have been initiated, and the last 4 centres are finalizing the documents, and expected
tobe initiated within the next weeks.As of today 24 patients havebeen randomized intothe study.
Recruitment is progressing but going slower than hoped for. We will have an increased focus on
this, and of course also discuss how this can be improved at the next investigator meeting to be
held in May.
Please find the detailed updated status of the trial centres attached to this letter to your notice.
0
2
4
6
8
10
12
14
CERTiFy patient recruitment 2014-04-06

2. CERTiFy publicationin TRIALS:
The study protocol has now been published in the TRIALS journal
(http://www.trialsjournal.com/content/15/1/75)
We strive to conduct the CERTiFy study in an ethical and rigorously scientific manner to clearly
demonstrate the value of Cerament BVF fortreatment of tibia plateau defects.
For this reason we acceptthe obligation togive investigators, physicians, and patients confidence
that we are reporting complete and accurate information about the study according to the
guidelines of the International Committee of Medical Journal Editors and the CONSORT
(Consolidated Standards of Reporting Trials) group. Publishing study protocols prior to
conduction of the study or publishing of the study results has been considered to improve
standards of medical research.
Making the protocolof the CERTiFy study available to all people through open access via TRIALS,
we aim to obtain feedback through peer review and enable readers to compare what was
originally intended with what was actually done, thus preventing both "data dredging" and post-
hoc revisions of study aims. Furthermore, we aim to enable researchers to see what studies are
underway and hence reduce duplication of research effort.
This important milestone will increase awareness of the study both in and outside Germany
further underlining the high quality of CERTiFy,and it willbe an advantage to us and the readers,
when we later publish and present the key results from CERTiFy.
Learning from initiationand monitor visits etc:
During the last monitor visits some questions and problems have been addressed by Dr. Becker.
Here, we would like to provide you some information and feedback that are most important for
the study conduction.
1) General information:
Any trial-related measures must exclusivelybecarried out by trial site personnel that have
been approvedbythe responsibleethicscommittee(EC)beforehand.
If you plan to extend yourstudy team, please send the required qualifying documents
(Curriculumvitae(CV),Financial disclosure(FD)and – ifavailable – GCPcertificates) to
the IZKS forthe attention of Dr. Becker:
InterdisziplinäresZentrumKlinischeStudien
z. Hd. FrauDr. D. Becker

3. Langenbeckstr.2, 55131Mainz
Documents will be submitted to the responsible EC and youwill be informed on
confirmation/approval foryour additional study personnel.
Please contact Dr. Becker(becker@izks-mainz.de) to receiveblank versions of the above
mentioned documents (CV, FD).
Activetrial participation also requires the registration of any investigator/trial assistant on the
Signature/Delegationlog(s.Investigatorsitefile,ch. 2) including authorization by the
Principal Investigator. Additionally, each investigator needs to sign the trial protocol (s.
Investigatorsitefile, ch. 4) prior to trial participation.
2) Electronic Case Record Form (eCRF)
2.1) Concomitantmedication
According to the File Note issued on 2013-09-18, all medication taken during the entire trial
duration is to be documented in the eCRF concomitantmedication form EXCEPT FOR
 Medication administered during anaesthesia/recorded on the anaesthesia protocol
 Fluid infusions/volume therapy related to trial surgery
 Intraoperativemedicationis standardizedandassumedto have no impact ontrial
outcome
2.2) Intraoperativebloodloss
Intraoperative blood loss is documented as the difference between total volume collectedand
rinsing fluid volume with an accuracy of ±25 ml.
 Themethodchosenforthe interruptionofbloodsupplyshouldbeappliedconsistently
forboth treatment groupsto avoidbiasin the data collected
3) Trial surgery and post-operative care
Whenever possible, please DO NOTUSE
 pain catheters
 analgesics pumps/PCA therapy

4.  Theaim isto minimizea bias in pain assessmentdata
(primaryoutcomecriterion!)aswell as the infectionrisk
 In case youconsideroneofthesemeasures indispensableforappropriatepatientcare,
pleasecontactthe Coordinatinginvestigator(CI)inadvance
4) Investigator Site File (ISF; “Prüfarztordner”)
4.1) Correctuseofthe ScreeningLog
The Screening Log is used to document only those patients who gavewritten consent
after beingfullyinformed aboutthe trial. For patients that turn out being not eligible for
trial participation after having given informed consent (“Screening failures”),please
indicate on the screening log the reason why these patients could not be randomized.
5) SubmissionofX-rayimages
X-ray images taken during the trial should be submitted to the PI center in electronic form
(CD) after trial visits4 and7:
 NO PERSONAL/IDENTIFYING DATAoftrial participants onCD/in file names/images
 DICOM formatif possible (if not, JPEGimages can be evaluated, as well)
 Label CD withnumber and name of yourtrial center, subject ID (Patienten-Nr.) and
examination/trial visit dates
Please submit your data forthe attention of PDDr. Hofmann:
Zentrum für Orthopädie und Unfallchirurgie
z. Hd. Herr PD Dr. A. Hofmann
Universitätsmedizin Mainz
Langenbeckstr. 1, 55131 Mainz

5. Learning from the first 8 patient that have concluded the study:
Because the results of primary/secondary outcomemeasures willbe assessed after the closure of
the database, we cannot report on preliminary results. Patients, who already concluded the last
visitin the study,did notexperience any complicationsorserious adverse events associated either
with autologous bone grafting or Cerament BVF. The learning curve for accomplishing the visits
and documentation was quite steep and we made a quick progress in establishing internal
processes. The eCRF is easy to use and self-explaining. We hope to have provided users with an
easy tool to document all relevant data of the study.
CERTiFy posters have been finalised and are being distributed to
the centers:
Posters in A3 format describing inclusion and exclusion criteria
have been adapted withnames of site specific investigators and
your unique hospital logos.
They are now being distributed by the German BONESUPPORT
team, whowill assist you in placing the posters.
The aim with this poster is to act as a reminder to all involved,
and to createknowledge and awareness aboutthe study in your
clinics as such. Something that is known to facilitate successful
recruitment

6. Next (forth) investigator meeting:
The next investigator meeting willtake place May 23rd, 2014, from10 – 14 (15) at the Frankfurt
Airport. This is the day before the ESTES annual meeting also to be held in Frankfurt
http://www.ectes2014.org/
A separate invitation with detailed agenda will follow beforethe meeting
Yours sincerely
PDDr. med. Alexander Hofmann Prof.Dr. med. Dr. h. c. PolM. Rommens

7. Status of the CERTiFy Trial Centers as of 2014-04-04
Center Contract
Trial
documents
Ethics
Committee
Initiation
Patients recruited (in
treatment/finished/drop-
out)
01 Mainz n. a.    18.04.2013 12 (3/8/1)
02 Murnau     10.07.2013
0
center discontinuation is under
discussion
05 Worms     10.09.2013 0
03 Köln     20.08.2013 2 (2/0/0)
08 Koblenz     13.11.2013 1 (1/0/0)
07 Rüsselsheim     10.10.2013 0
04 Fulda     02.09.2013 0
11 Münster     21.01.2014 1 (1/0/0)
10 Düsseldorf     10.12.2013 0
09 Duisburg     27.11.2013 0
Heidelberg1
latest enquiry on 02.04.14.1

final, not yet
signed

in progress
  0
12 Bad Homburg     31.01.2014 0
06 Lübeck     18.09.2013 8 (4/2/2)
Aachen2
latest contact on 03.04.14

at legaldept.

partially
available
  0
Frankfurt3
latest contact on 03.04.14
 
in progress
  0
Ludwigshafen4
latest contact on 03.04.14

final, signing
in progress

partially
available
  0

8. CERTiFycontactdetails:
Dr. Stanislav Gorbulev
E.mail: gorbulev@izks-mainz.de phone +49 (0) 6131 17 9917
AddressforX-raysubmission:
PDDr.med. Alexander Hofmann
Zentrum für Orthopädie und Unfallchirurgie
Universitätsmedizin Mainz
Langenbeckstr. 1
55131 Mainz