Full Service CRO
2Syntax for Science S.L. | www.syntaxforscience.com
Small enough to care, big enough to cope
We are a specialized team with a real passion for quality and improvement.
EXPERIENCED TEAM HIGH-QUALITY SERVICESFOCUSED ON CLIENTS
Head of Biometry(Marta Rodriguez)
Quality Assurance(Remei Sanchez)
Organization Chart
Chief Executive Officer(Juan V. Torres)
Chief Clinical Operations Officer(Lidia Almirall)
Clinical Operations Department
Chief Management Officer(Azahara Moreno) Chief Medical Officer
(César García-Rey)
Biometry Department
Syntax for Science S.L. | www.syntaxforscience.com 3
4Syntax for Science S.L. | www.syntaxforscience.com
Management Team
Juan V. Torres, MSc. Chief Executive Officer
Statistician with over 12 years
experience in clinical research.
Active member of the statistical
community: ISCB, SEB, and SoCE
Lidia Almirall, MSc.Chief Clinical Operations Officer
Biology Degree and MBA, with
more tan 20 years experience in
drug development.
César Garcia-Rey, MD.Chief Medical Officer
Specialist in Clinical
Microbiology with more than
15 years experience in clinical
research
Author of over 60 papers with
more than1.850 citations
5Syntax for Science S.L. | www.syntaxforscience.com
Services Overview
Medical Consultancy
Study Design
Regulatory Activities
Project Management
Site Management
Risk-based Monitoring
Data Management
e-Data Capture (EDC)
Biostatistics
Medical Writing
6
Therapeutic Areas
21
14
12
8
54
3 32 2 2 2
8
0
5
10
15
20
25
Number of projects by therapeutic area
7Syntax for Science S.L. | www.syntaxforscience.com
Study Phases
6
9
5 5
29
8
3
1
13
0
5
10
15
20
25
30
35
Phase I Phase II Phase III Phase IV Observational PredictionStudy
MedicalDevice
Meta-analysis Consultancy*
No. Projects by phase
25
55% 45%
National International
8
Publications
9
Publications II
10
Medical Consultancy:
• Scientific advice on clinical trial planning
• Recommendations for future studies/development
• Provision of therapeutic area and product training
• Benefit-risk analyses
• Clinical expert statements
• Development and update of reference product
information
Syntax for Science S.L. | www.syntaxforscience.com
11
Project Management :
A Project Manager is allocated to each project with the following responsibilities:
• Primary contact per project/client
• Elaborates all study plans (i.e. Regulatory Plan, Communication plan, etc.)
• Ensures that the study is performed on budget, quality, time and by the appropriate staff at
each project stage
• Reporting project progress
• Elaborates the study specific Risk-Based Monitoring Plan
Syntax for Science S.L. | www.syntaxforscience.com
12
100% Transparent
Our project management
technology provides real time
updates to sponsors about the
project status:
• Tasks
• Timelines
• Responsibilities
• Workload
• GANTT
Syntax for Science S.L. | www.syntaxforscience.com
13
Accomplishment of Regulatory activities according to local
Clinical Research regulations :
The Regulatory Expert will ensure that the study follows the “Guidance for Industry E6 Good
Clinical Practice: Consolidated Guidance” (ICH GCP guidance (E6) /FDA, April 1996 and at the
local level, all applicable laws / Norms of the Health Authorities of the country / region where the
study is carried out.
Related activities:
• EC and RA approval/authorization and
required communications
Syntax for Science S.L. | www.syntaxforscience.com
14
Essential documentation:
Essential documentation will be managed by the Clinical Trial Assistant (CTA) in accordance to
the “Guidance for Industry E6 Good Clinical Practice: Consolidated Guidance” (ICH GCP
guidance -E6 /FDA, April 1996):
“8.1. Essential Documents are those documents that individually and collectively permit evaluation
of the conduct of a trial and the quality of the data produced. These documents serve to
demonstrate the compliance of the investigator, sponsor, and monitor with the standards of GCP
and with all applicable regulatory requirements.”
“CTA acts as a link between all team members to ensure that all administrative activitites related
to clinical trials are completed”
Syntax for Science S.L. | www.syntaxforscience.com
15
Site Management activities:
Site Selection activities (performed by a monitor) will take place to ensure that the
Investigators have the qualifications and adequate resources as specified in the “Guidance
for Industry E6 Good Clinical Practice: Consolidated Guidance” (ICH GCP guidance (E6)
/FDA, April 1996.
Related activities:
• Elaboration of feasibiltity questionnaries
• Own therapeutic experts data base
• Site approach depending on Sponsor’s requirements
(direct/annonimized)
• Selection, contracts, and payments management
Syntax for Science S.L. | www.syntaxforscience.com
16
Clinical Monitoring:
Monitoring activities will take place in accordance to the “Guidance for Industry E6 Good Clinical
Practice: Consolidated Guidance” (ICH GCP guidance (E6) /FDA, April 1996
5.18 Monitoring/ 1. Purpose:
The purposes of trial monitoring are to verify that:
(a) The rights and well-being of human subjects are protected.
(b) The reported trial data are accurate, complete, and verifiable from source documents.
(c) The conduct of the trial is in compliance with the currently approved protocol/amendment(s), with GCP, and with
applicable regulatory requirement(s).
5.18.2 Selection and Qualifications of Monitors
(a) Monitors should be appointed by the sponsor.
(b) Monitors should be appropriately trained, and should have the
scientific and/or clinical knowledge needed to monitor the trial
adequately. A monitor’s qualifications should be documented.
(c) Monitors should be thoroughly familiar with the investigational
product(s), the protocol, written informed consent form and any other
written information to be provided to subjects, the sponsor’s SOPs,
GCP, and the applicable regulatory requirement(s).
Syntax for Science S.L. | www.syntaxforscience.com
17
Risk-based Monitoring:
A Risk-based approach will take place in accordance to the “Guidance for Industry –Oversight
of Clinical Investigations - A Risk-Based Approach to Monitoring”/FDA, August 2013
• Risk-based monitoring approach (established in the Study Monitoring Plan)
• Fix number of monitoring visits per project (not per site)
• Flexible assignation of visits per site: Flexible assignation based on
pre-established risks
• Flexible source data verification percentage
• Flexible percentage in each visit based on pre-established risks
Syntax for Science S.L. | www.syntaxforscience.com
18
Traditional on-site monitoring versus centralized risk-based monitoring
• FDA encourages centralized risk-based monitoring.
• State of the art methods. International collaboration for the development of a centralized
risk-based monitoring system.
100% 100% 100% 100% 5% 40% 5% 85%
Syntax for Science S.L. | www.syntaxforscience.com
19
Clinical Data Management:
• Consulting and Implementation of Data Management Strategies
• CRF Design
• Data Validation
• Query Management
• SAE Management
• Data Entry
• CDISC Implementation
• Data consolidation and conversion (CDISC SDTM)
• Electronic Data Transfer
Syntax for Science S.L. | www.syntaxforscience.com
20
Electronic Data Capture (EDC) :
• Capture Cleaner Data
• Engage Patients from their own devices (electronic patient-reported outcome, ePRO)
• Accelerate Your Research
• One single dedicated server and backup for your data
• CDASH CRF Library
• Electronic Clinical Data Management System (based on SAS)
• Investigator and monitor training material
• Risk Based Monitoring
Syntax for Science S.L. | www.syntaxforscience.com
21
Medical Coding :
Dictionaries:
• WHO Drug / ATC Country Drug Registries
• MedDRA
• ICD-10
• Other dictionaries
Technology:
• Management of multiple medical coding dictionaries
• Splitting of terms
• Version control
• Traceability from verbatim to reported terms
• Fast & Accuracy
Syntax for Science S.L. | www.syntaxforscience.com
22
Biostatistics :
• Study design
• Statistical analysis plan
• Sample size calculation
• Randomization
• Interim-analysis
• Meta-analyses
• Indirect comparisons
• PK/PD analysis
Syntax for Science S.L. | www.syntaxforscience.com
• Statistical Programming in SAS® of tables, listings and figures
• Mapping of old studies to CDISC format (SDTM, ADaM)
• Derived datasets
• Statistical report and appendices
• Validation or audits of stats work accomplished by others
• Meta-analyses
• Exploratory analyses
• Biomarkers validation
23
Medical Writing:
• Statistical technical sections: methods and results
• Clinical study reports (ICH E3)
• Protocol statistical sections
• Scientific papers
• Abstracts, posters and oral presentations
Syntax for Science S.L. | www.syntaxforscience.com
24
On-line Clinical Survey:
An affordable and trustworthy online tool to conduct clinical surveys.
System Features:
• Accessibility
• Security
• Customizable design
• Affordable pricing
Our Services:
• Full suport
• Helpdesk
• Result analysis
Syntax for Science S.L. | www.syntaxforscience.com
25
Mod & Sim PK/PD
We develop pharmacokinetic and pharmacodynamic population models that associate dose-
concentration with the concentration-effect relationship of drugs characterizing the drug
behavior.
Syntax for Science S.L. | www.syntaxforscience.com
WE WILL ASSIST YOU IN:
• Giving advice on drug development
• Pharmacokinetic studies and pharmacodynamic population
models
• Biostatistics analysis
• Bioequivalence studies
26
SOP Template FormWorking
Instructions
Quality System* 8 9 2 -
Information Technology 2 6 - 2
Data Management 16 15 20 7
Biostatistics 7 8 2 1
Clinical Operations 17 18 23 3
Human Resources - 6 7 4
Administration - 16 1 2
Good Clinical Practice, and 21 CFR part 11 compliance.
A total of 202 QS Documents reviewed by an experienced Auditor
* Fully compliance with LOPD
Quality Assurance System:
Syntax for Science S.L. | www.syntaxforscience.com
AUDITS: An external Audit (system & project audit) has been performed in June 2016 in a Phase III trial managed by
Syntax for Science with the result of “0” major findings.
27
SECURITY AVAILABILITY TRACEABILITY QUALITY
• Password Policies
• Firewall
• Anti-Hacking System
• User Access Groups
• Anti-Theft Systems
• UPS System
(Battery)
• Backups
• On-site, hourly
• Out-site, weekly
• Remote Access
• VPN (Encrypted)
• Web (HTTPS)
• Audit Trail
• File Access
• Server Access
• Control Version – GIT
• Data
• Programs
• Documents
• 21 CFR Part 11
• GAMP 5
• Life Cycle
• Business Continuity Plan
• Risk Assessment
• Training
IT Computer System :
Syntax for Science S.L. | www.syntaxforscience.com
28Syntax for Science S.L. | www.syntaxforscience.com
Some of our clients:
29Syntax for Science S.L. | www.syntaxforscience.com
Case Studies
A sample of our successful work
30
Clinical Operations, phase III study
Syntax for Science S.L. | www.syntaxforscience.com
Challenges:
1. Pediatric study and Placebo arm. Vulnerable population.
2. Seasonal disorder (summer) vs. family availability (holidays). Low rate recruitment.
3. Performed by General Practitioners (Pediatrics) in Public Institutions. Inexperienced and overloaded research team.
Introduction:
The recruitment rate in a pediatric study conducted by General Practitioners (Pediatrics) in Public Institutions is always a
challenge due to the overload and inexperience of the investigator team and specific population. In this study, the
presence of a placebo-arm and the fact that the disease peaks seasonally, increased the difficulty of the recruitment rate.
Syntax Solutions:
1. Study design allowed patient to withdraw the study after 4 days of treatment if no improvement.
2. Spain: Non-recruiting sites were promptly closed and new identified ones with high projection figures were
opened. Study also opened in Mexico. Half of the recruitment reached in 8 months. A total of 54 sites were
activated at the end of the study.
3. Close communication with sites, re-trainings on GCPs/protocol, monitoring timetable according to site availability
(mostly afternoon).
31
Data management, Phase I
Syntax for Science S.L. | www.syntaxforscience.com
Challenges:
1. Handling a large volume of lab data.
2. Handling a large volume of queries.
3. Accomplishing tight timing requirements in order to deliver quickly the final database.
Introduction:
Phase 1 studies require collecting a large amount of safety data, and conduct an exhaustive validation in order to ensure
data quality. This clinical trial had two different cohorts, the first one consisted in dose escalation. The population was
enrolled at one unique site.
Syntax Solutions:
1. Conduct lab data transfers instead of entering all data into the eCRF.
2. Manage all quereis together (fired by eCRF + programmed using SAS).
3. Provide an ad hoc tool to accelerate the resolution of queries.
32
PK analysis, Phase I
Syntax for Science S.L. | www.syntaxforscience.com
Challenges:
1. Dose Escalation Safety Committee (DESC) needs PK parameter estimations to decide the next dose.
2. The central laboratory had a delay, and provided partial data (no post-infusion concentrations).
3. Estimate parameters with limited number of post-infusion data.
Introduction:
Phase I clinical trials are an essential step in the development of new drugs, establishing the recommended dose for
incoming trials. The objectives of the dose escalation cohort were both assessing safety and exploring the PK profile.
Non-compartmental analysis were considered per protocol.
Syntax Solutions:
1. Being flexible to process each patient depending on their data availability.
2. Eventually the elimination rate was calculated using infusion data fitting
compartmental models.
3. Although few experimental post-infusion points were available, the AUCinf
was calculated considering as 0 the BLQ observed at the next time point.
33
Diagnostic tool
Syntax for Science S.L. | www.syntaxforscience.com
Challenges:
1. Provide to the investigators an easy way to identify patients at risk.
2. Low prevalence of the disease, and long and heterogeneous natural history.
3. Disseminate knowledge about a rare disease.
Introduction:
Rare diseases are difficult to diagnose due to the lack of knowledge and tools about the disease. Thus many patients are
missed to diagnose and failed to be appropriately treated.
Syntax Solutions:
1. Development of different tools based on signs and symptoms:
2. Suspicion index for general population
3. Suspicion index for pediatric population
4. Algorithm targeting risk subgroups
5. The study was conducted using retrospective data.
6. Tools were developed in both electronic and paper format.
34
Prognostic tools
Syntax for Science S.L. | www.syntaxforscience.com
Challenges:
1. Recruit enough subjects to obtain reliable results on a very specific population (bone metastasis patients with history
of prostate cancer).
2. How to design a study with sensible ethical concerns.
Introduction:
Prognostic estimates can be used to inform about likely outcomes of the patient’s disease. The physician can use
estimates of prognosis as a guide for ordering additional tests and selecting appropriate therapies. It can also be used
to define better populations for new clinical trials.
Syntax Solutions:
1. The study was conducted using data from a biobank.
2. Discussion of the design with the sponsor and key
opinion leaders provided an appropriate design which
overcome the ethical concerns.
35
Expert’s experience survey
Syntax for Science S.L. | www.syntaxforscience.com
Challenges:
1. Provide an easy tool to gather information.
2. Follow-up participation and ensure response rate.
Introduction:
Sponsor needs information about how the physicians are currently screening and diagnosing patients with a rare
disease, and which techniques they use to assess their health.
Syntax Solutions:
1. Implement an online survey.
2. The survey was distributed to all physicians in the Sponsors’
network by email.
3. Weekly response follow-up and reminders to non responders.
36
Delphi – Consensus meeting
Syntax for Science S.L. | www.syntaxforscience.com
Challenges:
1. Lack of international consensus and clear guidelines about when prescribe
expensive treatment.
2. Obtain consensus among key opinion leaders.
Introduction:
The Delphi method is a structured communication technique which relies on a panel of experts. The experts answer
questionnaires in two or more rounds. After each round, an anonymous summary of the answers as well as the reasons
they provided for their judgments is provided. During this process, experts are encouraged to revise their earlier answers. It
is expected that the range of the answers will decrease converging towards the "correct" answer.
Syntax Solutions:
1. Obtain a consensus about how to diagnose, treat and follow up patients with a
rare disease by the creation of a clinical guidance.
2. Set up a face to face meeting with the scientific committee
3. Set up a survey
37Syntax for Science S.L. | www.syntaxforscience.com
Digital tools
38Syntax for Science S.L. | www.syntaxforscience.com
Challenge us and confirm that
we are your partner!
PALMA DE MALLORCA
ParcBit, Edif. NAORTE A 1º 5ª
Ctra. Valldemossa Km. 7.4
07121 – Palma de Mallorca – Spain
Tel: +34 971 910 842
[email protected] | www.syntaxforscience.com
Thank you!Let’s start Research!
BARCELONA
C/ Consell de Cent 375, 2-1
08009 – Barcelona – Spain
Tel: + 34 93 464 46 47