Services Portfolio

Clinical Trial Management

Practice Highlights

Clinical Trial Management (CTM) is the single largest core service offering at Karmic and we possess significant expertise in delivering high quality, GCP compliant, end-to-end CTM services. Some of the highlights of our CTM practice are:

• Robust track record of 56 Executed Clinical Trials recruiting 11,592 patients across 14 therapeutic areas and 40+ indications including Oncology, Cardiovascular, Diabetes, Neurology, Ophthalmology, Auto Immune Diseases and Medical Devices
• Pan-India Network of over 2000+ Sites, 201 Active Sites with strong GCP and Global Trial experience across 25+ cities including Tier I, Tier II & Tier III cities
• Rapid Site Feasibility using kSiteX™, our proprietary site feasibility model ensures that we process feasibility requests within 48 to 72 hours with in-depth information on Disease Prevalence, Epidemiology, Standard of Care, Study Challenges and Resolutions, Preliminary Site List and Budgets
• Crunched Study Start-up Timelines and Accelerated Patient Enrolment and leverage of kTrials™, Karmic’s proprietary web-based CTMS for robust project planning, tracking and reporting of key trial metrics and exceptions on a real-time basis
• Consistently meeting Stringent Trial Metrics

Service Offerings

Comprehensive Services across all activities of a clinical program:

• Study & Site Feasibility: Preliminary Site Feasibility closed within 48-72 hours, access to a 2000+ Site Database comprising of experienced GCP sites, rapid connect with investigators and CRCs and a diligent Site Qualification process involving a detailed checklist as well as a Pre-Study Site Selection Visit (PSSV)
• Study Planning & Initiation Activities: 4-6 weeks typical trial start-up timelines post regulatory approval, robust site initiation training covering protocol and study procedures, GCP training as well as EDC, Informed Consent, Source Documentation and Safety Reporting training
• Clinical Monitoring: Extensive Monitoring experience, 500+ monitoring visits handled on an annual basis, GCP trained team of CRAs with 3-7 years of monitoring experience, 100% Source Document Verification, maintenance and continual review of Protocol Deviations/Violations Log, ICD Deviation Log and Issue Action Log to ensure compliance
• Medical Monitoring: Medically qualified team of Medical Monitors (MBBS, MD) for robust safety oversight and medical value adds on patient eligibility, safety management and reporting, handling medical queries from site etc. throughout the study
• Safety Management & Reporting: Strong Safety expertise and an independent Safety team for handling SAE Narratives, Safety Database Management, Regulatory Reporting, DSMB/Clinical Events Committee Reporting, PSUR Reporting etc.
• Central & Local Lab Management: Strong understanding and experience with lab procedures, normal ranges, calibration, IP & Sample Shipping etc. Tie-ups with key CAP, CLIA and NABL accredited, GLP class Central Labs and strong audit procedures
• IP Management: Strong IP Management & Accountability SOPs, Tie-up with GLP certified IP Management vendors for managing the entire IP value chain from import through packaging, labeling, storage, distribution and destruction. Use of IVRS for randomization, IP tracking and inventory management
• Site & Study Close-out Activities: Site & Study closure as per laid down SOPs, retrieval of all CRFs, closure of all queries, IP accountability and Return, completion of all study logs and SMF etc.

Value Proposition for Sponsor

• On Budget, On Schedule, GCP Compliant Execution for all studies
• 25% shorter trial timelines with rapid project jumpstart & accelerated recruitment
• 35%+ Cost Savings leveraging the India Advantage
• Strong Medical Oversight to all studies including protocol design inputs, medical monitoring, trend analysis of safety and efficacy parameters, clinical correlation of data
• Full Trial Visibility and Custom Reporting to sponsor leveraging kTrials™, Karmic proprietary CTMS platform

Clinical Data Management

Practice Highlights

Our Clinical Data Management group is one of the most mature practices in the Karmic full services portfolio wherein we support end-to-end CDM activities as per GCDMP and 21 CFR Part 11 compliance. Some of the highlights of the practice are:

• Robust track record of 61 Executed Paper & EDC based Global Clinical Data Management studies involving 50,000+ CRFs across Phase II, III, IV, Post Marketing Surveillance, Epidemiology, Retrospective/Prospective, Registry and Bio-equivalence studies.
• Dedicated Team of 24 professionals with strong domain and biometrics expertise and understanding of and adherence to global standards including 21 CFR Part 11, CDISC/CDASH, GCDMP, SDTM, ADaM and HIPAA
• 21 CFR Part 11 compliant infrastructure comprising best-in-class owned and hosted systems: Clintrial 4.6, kClinion 2.0 EDC, OC / RDC, Inform, Rave, SAS 9.2 and Medical Dictionaries: MedDRA 14.1, WHO-DD 3.0
• Consistently meeting Stringent CDM SLAs:

Service Offerings

Comprehensive Services across all activities of a clinical program:

• Study Set-up Activities: Initial CDM Study Set-up closed within 72 hours with Data Management Plan, Quality Plan and Data Master File (DMF) drafted and approved by Sponsor.
• CRF Design: CRFs are designed using global CRF templates with pre-defined panels and formats specific to each therapeutic area in 2-3 business days and are followed by extensive review from the medical writing, statistical and clinical operations team.
• Database Design, Testing & UAT: User Requirements Specifications and Functional Specifications are typically developed within 5 business days from receipt of CRF and reviewed by the statistical and medical writing teams followed by database design, testing and UAT (User Acceptance Testing) using good and bad data. Karmic has extensive programming experience on Oracle, PL/SQL and SQL databases and a thorough Performance Qualification (PQ) for all studies is done prior to study go-live.
• Edit Check Programming: Logical Edit Checks are programmed during database design stage to ensure that all critical safety and efficacy parameters turn in valid values while ensuring reduced irrelevant queries. The checks are further programmed to raise auto queries and apply self-evident corrections where feasible.
• Data Entry & Verification: For paper CRFs, Karmic uses 100% blinded, double data entry followed by 100% data verification by Data Manager.
• Discrepancy Management: Discrepancy Management involving query generation, intensive site follow-ups for speedy query resolutions, application of self-evident corrections, query ageing tracking and reporting.
• SAE Reconciliation: Maintenance of an SAE database and ongoing SAE reconciliation with Safety Database from Sponsor / Pharmacovigilance team
• Medical Coding: Team with robust training on ICD 10 and CPT standards and medical coding on MedDRA 14.1 (Adverse Events) and WHO-DD 3.0 (Concomitant Medication)
• Data Quality Check & Review: Three levels of data quality check and review involving the CDM Team, Statistical Team and Medical Team to review data for completeness and correctness, missing values, units etc. and medical review for trend analysis and clinical correlation of anomalies
• Database Lock & Extraction: Comprehensive SOPs for data review, cleaning and query closure prior to database lock followed by direct data extraction to SAS for statistical analysis

Value Proposition for Sponsor

• 21 CFR Part 11 compliant delivery with high data quality and integrity
• Reduced costs and customized reporting leveraging kClinionTM, Karmic proprietary and highly scalable Electronic Data Capture (EDC) platform for late phase studies
• 40%+ Cost Savings leveraging the India Advantage

Bio-Statistics & Statistical Programming

Practice Highlights

At Karmic, we have a prolific Bio-Statistics and Statistical Programming group that is abreast with leading edge statistical and programming techniques for delivering quick and efficient analysis results. Some of the highlights of the practice are:

• Karmic has a prolific body of 60+ Statistical/Analytical Modeling, Programming and Analysis Projects across Phase I, II, III, IV, Post Marketing Surveillance, Epidemiology, Retrospective/Prospective, Registry and Bio-equivalence studies.
• Our team comprises of an 8 member Statistical and Analytical practice group with a cumulative experience of 30+ person years and includes Statisticians, Business Analysts and SAS Programmers to handle statistical and analytical requirements.
• We leverage SAS 9.2, SAS Enterprise Guide 4.3 and SAS EBI to ensure full compliance to CDISC, SDTM and ADaM standards and have good understanding of complex techniques such as Generalized Estimating Equation, Repeated Measurements, Bayesian Techniques, Mixed Modeling, Adaptive Trial Designs, Meta-Analysis, etc.
• We work across model development, programming and validation assignments and have applied multiple tools and techniques to solving complex analytical problems including Regression Analysis, Conjoint Analysis, Factor Analysis, Predictive Analysis, Discriminant Analysis, Multi-Variate ANOVA etc.
• Karmic is currently developing an exhaustive set of therapeutic area wise global libraries consisting of validated macros and re-usable frameworks for enhanced programming efficiency and rapid statistical analysis
• Consistently meeting Stringent Bio-Statistics SLAs:

Service Offerings

• Protocol Statistical & Design Inputs: Our Bio-Statistics team gets involved on all clinical projects from Day 0 and provides value-added inputs on the statistical sections of the protocol, sample size etc.
• Sample Size Calculation: We do extensive literature search and turnaround sample size calculations within 1 business day of sponsor request across several study designs including superiority, non-inferiority and equivalence trials.
• Randomization: We generate randomization schedules including stratified, block and cluster randomization for blinded studies within 1 business day of sponsor request.
• Statistical Analysis Plan / Tables, Figures and Listings Development: Karmic Statisticians develop an in-depth Statistical Analysis Plan in line with ICH E9 standards alongwith the appropriate statistical tests, shell tables, figures and listings that get reviewed and approved by the sponsor.
• Statistical Programming & Validation: Karmic uses extensive libraries, macros and GPP compliant practices to develop efficient and validated output. Karmic follows three levels of validation: Highly Critical, Critical and Non-Critical including application of double programming and cosmetic output review techniques. We further use dummy data dry runs to ensure programming readiness prior to initiating actual analysis.
• Interim Analysis & Final Analysis: We typically deliver Interim and Final Analysis with good statistical interpretation within 21 business days of receiving clean data. Prior to starting the output generation, we do extensive data review activity using SAS tools. Further the statistical report goes through statistical as well as medical QC before being finalized.
• Meta-Analysis: Karmic also supports meta-analysis across multiple study data over a defined historical period wherein we first do a systematic review of literature based on which we apply techniques for data homogeneity / heterogeneity based on which we use random and mixed effect models, forest plots etc. to provide meaningful analysis that addresses the research hypothesis.
• Adaptive Trial Designs: Karmic has done a few adaptive design trials and this is an evolving area wherein we are providing inputs on modification of Phase II and Phase III  trials without interfering with the trial’s integrity and validity by doing interim analysis of study safety and efficacy data and providing decision support to sponsors for modifying remaining trial design as applicable.

Value Proposition for Sponsor

• Low Error and quick turnaround of statistical programming, analysis and reporting activity
• Deep domain expertise and understanding of global standards such as GPP, SDTM, ADaM
• High proficiency on SAS 9.2, SAS EG 4.3, SAS EBI etc. with customized reporting
• Value added inputs on specialized areas: Protocol Design, Statistical Methods, Adaptive Designs
• 40%+ Cost Savings leveraging the India Advantage

Medical Writing

Practice Highlights

SCIENCE is one of the cornerstones of value addition at Karmic wherein we support several NCE / NBE programs right from inception and lend strong scientific and medical expertise to the clinical development strategy. Some highlights of the medical writing practice are:

• Karmic has experience of handling a 100+ New Protocol Development projects across 15+ therapeutic areas and 40+ indications including NCEs / NBEs / Medical Devices etc. across Oncolgy, Cardio-Diabeto, Neurology, Ophthalmology, Infectious Diseases, Acute Diseases etc.
• Our medical writing team comprises of medically qualified doctors (MBBS / MD / BHMS / BAMS) with deep scientific domain expertise, medical drafting and review skills and experience with several medical journals including Pubmed, Lancet, ASCO, Nature etc.
• We have strong proficiency across the end-to-end medical writing portfolio including Protocols, IB, CRFs, ICFs, CSRs, Medical Manuscripts etc. wherein we have standard ICH E2, E3, E6 and Schedule Y based templates, CRF libraries of standard panels to provide rapid turnaround
• Our Safety team handles reporting including Safety Narratives, PSURs, SUSARs, DSMB and CEC reporting and provides strong safety and medical monitoring oversight to all programs
• We further create a study specific Protocol & Clinical Review Panel for ongoing data review of trends, outliers, clinical correlation as applicable
• Focus on developing a validated Biomarkers database as well as detailed dossiers on novel bio-markers that can be applied to trials. We also provide expertise in developing esoteric diagnostics alongwith our lab partners for novel tests.
• Consistently meeting Stringent Medical Writing SLAs:

Service Offerings

• Protocol Synopsis Development: The Karmic medical writing team supports quick development of protocol synopsis post doing an exhaustive literature search to incorporate inclusion/exclusion, primary, secondary and safety efficacy end-points and schedule of assessments. This provides our sponsors with a baseline to initiate a focused protocol design process as well as helps with preliminary feasibility and budgeting.

• Protocol Design: Karmic has experience of designing over 100 protocols across 15+ therapeutic areas and 40+ indications. We have pre-defined ICH E2 and Schedule Y compliant templates and an experienced team to handle literature searches, assumptions validation and drafting. We further incorporate a protocol review expert panels with representation from medical doctors and therapeutic experts to critically review and provide key inputs to protocol.

• CRF Design: We have extensive CRF libraries with standard panels for quick assembly of CRFs. We further annotate CRFs as well as handle several EDC and eCRFs.

• ICF Design: Karmic again has extensive experience with ICF designs to ensure language in line with GCP requirements as well as covering all stipulated local, regulatory and country specific requirements.

• CSR Development: Karmic has extensive experience developing Clinical Study Reports in line with ICH E3 and Schedule Y requirements. Our library of pre-defined templates and drafting procedures ensure that we are able to turnaround Clinical Study Reports within 21 business days.

• Medical Manuscripts: We have drafted several papers and manuscripts across leading Indian and Global journals and support our sponsors with journal identification, selection, drafting of manuscripts as per journal specific requirements, submissions and publications.

• Custom Literature & Patent Research: Karmic provides support across several custom literature research, patent research and medico-marketing assignments leveraging over 50 medical journals

• Custom Bio-Marker Research & Dossier Preparation: Karmic is currently working on a validated bio-marker library across 4-5 key therapeutic indications and preparing extensive bio-marker dossiers for application on clinical trials.

Value Proposition for Sponsor

• Immense Medical Domain Expertise and Knowledge with high quality scientific and research inputs especially for Phase II & Phase III programs involving NCEs / NBEs
• One stop shop for all medical writing assignments with a full portfolio of services
• Rapid turnaround on critical documents including Protocol, CRF, ICF, CSR etc.
• 40%+ Cost Savings leveraging the India Advantage

Safety & Pharmacovigilance

Practice Highlights

Pharmacovigilance is an emerging practice area for Karmic. We are currently building a Pharmacovigilance team consisting of ICH-GCP trained MBBS / MD doctors with several years of Pharmacovigilance and safety handling experience and a full suite of Pharmacovigilance services including:

• 24X7 Contact Center and Safety Reporting helpdesk
• AE/SAE Logging, Handling & Tracking
• Case Processing & Evaluation
• SAE Narratives Writing
• Medical Coding
• PADER & PSURs Generation
• SUSARs Reporting
• Global Data Safety Monitoring Boards (DSMBs) & Clinical Events Committees (CEC) Reporting

Regulatory Consulting

Practice Highlights

Karmic’s core clinical services are delivered on a strong platform of regulatory expertise. We provide end-to-end regulatory support including Pre-Approval Dossier & Documentation Support, Marketing Authorization Approval, Post Approval Support and Medical & Technical Writing services to our clients.

Our team comprises of experienced regulatory consultants with 100+ person years experience and strong knowledge of US-FDA, EMEA and other markets wherein we can handle pre-IND through marketing approval in as many as 96 countries. We further have a strategic partnership with a leading e-submissions company for CTD/eCTD submission through dedicated gateways. Our regulatory services include:

• Regulatory Strategy for NCEs, NBEs, Generics, Medical Devices etc.
• Core Dossier Compilation and Management
• Regulatory Submissions & Approvals (Pre-IND, IND and Marketing Approvals)
• NDA/ANDA Filings, DMF’s etc.
• ICH/ASEAN based CTD/eCTD Regulatory Submissions
• CTD Summaries, Overview and Expert Report
• Regulatory Intelligence & Updates

Trial Support Services

Central Lab / Local Lab & Logistics Management

Karmic works with a select set of CAP (College of American Pathologists, USA), CLIA (Clinical Laboratory Improvement Lab, USA), NABL (National Accreditation Board Limited, India) and ISO (International Standards Organization) accredited / GLP (Good Laboratory Practices) class laboratories including Central and Local Laboratories on a pan-India basis to ensure seamless laboratory and diagnostics test processing.

Our preferred laboratory partner comes with over 30 years experience and has 65 state-of-the-art-laboratories and over 350 collection centers across India and globally with a menu of 4000+ tests including highly specialized investigations involving Biochip and DNA sequencing technologies. The laboratory handles upwards of 10 Million tests a year. We further work with our partners to develop and validate new, innovative and esoteric diagnostics tests that are applied to clinical trials.

Highlights of our laboratory support services for clinical trials include

• Fully automated top-of-the-line instruments and a menu of over 4000 tests, over 1200 specialized tests with a broad spectrum offering across 16+ therapeutic areas
• Specimen Archival using secure facility with temperature and humidity control to ensure full sample integrity audit trial
• Pan-India logistics network with 350+ collection centers, tie-up with leading courier companies, express pick up of priority samples to be turned around within short duration, specimens are transported as per Protocol requirements in refrigerated/frozen conditions with temperature data loggers (2 – 8°C / -20°to -70°C / 37°C)
• Transportation of specimens in accordance with Federal and Local Laws and in compliance with OSHA blood-borne pathogen standards

Investigational Product Management

Karmic works with its partners to provide a comprehensive set of Investigational Product (IP) Management services for clinical trials including IP Packaging, IP Labeling, IP Storage, Shipping and Destruction

• Access to GMP certified packaging and manufacturing facilities in India, Singapore, Europe and the US with ISO 9001, ISO 14001 and ISO 18001 (OSHAS) certifications
• Access to innovative methodologies, customized equipment and testing protocols for understanding and optimizing the drug protection process, solving drug-stability issues and accelerating ‘speed to market’ while optimizing packaging costs. Packaging services extend to solid, semi-solid, liquid, DEA (CI-V) and biotech clinical trial materials (CTM) and multiple types of blisters, strips, wallets etc. alongwith specialized labeling for clinical trials
• Access to 21 CFR Part 11 Interactive Voice Response Services (IVRS) / Interactive Web Response Services (IWRS) systems for real time clinical inventory and supply chain management.

Cardiac Safety, Radiology & Imaging Services

Karmic offers a full suite of Cardiac Safety, Radiology and Imaging services as applicable to a clinical trial through its partners:

• Cardiac Safety Services including 12-Lead ECG, Thorough QT (TQT) and Intensive QT Trials, Holter Monitoring, Cardiac Event/Trans-telephonic Monitoring (TTM), Echocardiography, Ambulatory Blood Pressure
• Monitoring, Wireless ECG Monitoring, ECG Stress Testing (ETT) and Impedance Cardiography
• Medical Imaging Review and Interpretation services for CT, PET, MRI, DXA, X-Rays, Ultrasounds etc. Board-certified Radiologists provide blinded, in-depth response review, especially against Oncology Recist 1.1 criteria
• Centralized, DICOM based Imaging repository for quick retrieval, review and tagging of images
• Typical review and interpretation turnaround within 24 hours, emergency / express review within 2 hours also available

Bio-Analytical Services

Karmic offers a full suite of Bio-Availability and Bio-Equivalence studies through its strategic partner. The partner lab has undergone US-FDA, WHO, MCC, MPA, AFSAAPS, BSG and ANVISA  inspections and has a 363 bed, 9 CPU, 34 LC-MS/MS infrastructure across three sites in India and 200+ validated bio-analytical methods.

Pre-Clinical Services

Karmic works with an OECD GLP certified pre-clinical lab to offer a full suite of pre-clinical services comprising Acute Toxicity, Sub Chronic Toxicity, Chronic Toxicity, Reproductive Toxicity, Mutagenicity, Carcinogenicity, Toxicokinetics etc. We also have a partnership with a European pre-clinical laboratory to offer advanced pre-clinical efficacy models in Oncology, Neurology and Diabetes.

Custom Staffing & Training

Karmic offers staff insourcing services for Project Managers, Clinical Research Associates, Clinical Research Coordinators, Clinical Trial Assistants, Bio-Statisticians, SAS Programmers etc. Apart from this, we also provide specialized training on ICH-GCP, CDISC, Informed Consent, Safety Reporting and other advanced topics for our sponsors. KarmaGyanTM, our in-house, web-based learning management systems has over 15 modules and 200 courses for online, real-time learning and assessment.

In-licensing & Outlicensing Support

Given that Karmic works with several innovator companies in the NCE / NBE / Medical Devices space as well as large global and Indian sponsors, we provide in-licensing and out-licensing support services by taking specific mandates from our clients and introducing them to opportunities that fit into their product portfolios. We further provide commercialization support in terms of helping with identifying CRAMs vendors for pilot to scale-up production.