IMPORTANCE OF CLINICAL TRIAL DISCLOSURE:
Any new medication that is developed has to prove in clinical trials that it is safe and effective. Providing access to information about clinical research studies and their results serves study participants, patients and their healthcare providers as well as the public at large. Clinical Trial Disclosure is making clinical trial information widely available to the general public and provides transparency in the clinical trials process.

Life sciences organizations are enabled to efficiently manage clinical trial registration and reporting of results to clinicaltrials.gov, EudraCT and other registries.It offers support to the entire process of gathering data by stakeholders for review and conducting checks against registry specific validation rules and generating XML files for upload to the registry.  It will also help companies to maintain compliance and consistency of data published in registries worldwide.

CLINICALTRIALS.GOV:
ClinicalTrials.gov is a web-based resource that provides patients, their family members, health care professionals, researchers and the public with easy access to information on publicly and privately supported clinical studies on a wide range of diseases and conditions, which is maintained by the National Library of Medicine (NLM) at the National Institutes of Health (NIH).

ClinicalTrials.gov contains information about medical studies in human volunteers.This web site and database of clinical studies is commonly referred to as a “registry” and “results database.” ClinicalTrials.gov does not contain information about all the clinical studies conducted in the United States because not all studies are required by law to be registered.

ClinicalTrials.gov was created as a result of the Food and Drug Administration Modernization Act of 1997 (FDAMA) and was made available to the public in February 2000.The ClinicalTrials.gov registration requirements were expanded after the FDA Amendments Act of 2007 (FDAAA).

The results database was made available to the public in September 2008. FDAAA 801 also established penalties for failing to register or submit the results of trials. In the US, a sponsor needs to submit the data for protocol results to CTGOV and independently goes to the FDA asking for approval to conduct the trial.

RESULTS DATABASE:
The ClinicalTrials.gov results database was launched in September 2008 to implement Section 801 of the Food and Drug Administration Amendments Act of 2007 FDAAA 801, which requires the submission of “basic results” for certain clinical trials, generally not later than 1 year after their completion date.Results information for registered and completed studies is submitted by the study sponsor or principal investigator in a standard, tabular format without discussions or conclusions. The results information that is submitted includes the following:

• Participant Flow: A tabular summary of progress of participants through each stage of a study, by study arm or comparison group. It includes number of participants who started, completed and dropped out of each period of the study based on the sequence in which interventions were assigned.
• Baseline Characteristics: A tabular summary of data collected at the beginning of a study for all participants, by study arm or comparison group. This data includes demographics, such as age and gender and study-specific measures.
• Outcome Measures and Statistical Analysis: A tabular summary of outcome measure values, by study arm or comparison group. It includes tables for each pre-specified Primary Outcome and Secondary Outcome and may also include other pre-specified outcomes, post hoc outcomes and any appropriate statistical analysis.
• Adverse Events: A tabular summary of all anticipated and unanticipated serious adverse events and a tabular summary of anticipated and unanticipated other adverse events exceeding a specific frequency threshold. For each serious or other adverse event, it includes the adverse event term, affected organ system, number of participants at risk, and number of participants affected, by study arm or comparison group.

RESULTS ENTRY AHEAD OF CLINICAL TRIAL:
Depending on the development stage of product, the phase of study and location, study results, including a description of the design and methodology, results of primary and secondary outcome measures, and safety, will be published. In general, the law requires study sponsors or designated principal investigators (PIs) to report summary results information within one year of completing data collection for the prespecified primary outcome, regardless of sponsor or funding source.

GENERAL RESULTS AHEAD OF CLINICAL TRIAL:
Participant Flow: Progress of research participants through each stage of a trial in a tabular format, including the number of participants who dropped out of the clinical trial.

Recruitment Details: Key information relevant to recruitment process for overall study, such as dates of recruitment period and types of location (e.g., medical clinic).

Pre-assignment Details: Definition: Description of any significant events and approaches for overall study (e.g., wash out, run-in, transition) following participant enrolment, but prior to group assignment.

Arm/Group: Arm/Group Title: Label used to identify the arm or comparison group.

Arm/Group Description: Brief description of the arm or comparison group to distinguish it from other arms/groups in the trial.

Period(s):  Discrete stages of a clinical trial during which numbers of participants at specific significant events or points of time are reported (There is no limit to the number of periods).

Period Title: Title describing a stage of the trial. Number of participants required at the beginning of the period.

Baseline Characteristics: A table of demographic and baseline data (study specific) for the entire trial population and for each arm or comparison group.

Results Described During/After Clinical Trial: Results of applicable clinical trials must be reported within 12 months following the primary completion date. Primary Completion Date is the date the final subject was examined or received an intervention for the purposes of final collection of data for the primary outcome, whether the clinical trial concluded according to the pre-specified protocol or was terminated. “Study Completion Date” is the final date on which data was collected.

Regardless of the outcome, after completion or termination of a clinical trial in patients, the results of the trial are posted according to current laws and regulations.

GENERAL RESULTS DESCRIBED DURING TRIAL:
Enrolment details: Participant enrolment into study details.

Completed: Number of participants completed the study.

Discontinuation details: Number of patients discontinued from the study.

Reason Not Completed: Additional information about participants who did not complete the period, if any.

Demographics of participants: (Ex., age, sex, race, etc.)

Laboratory results: Haematology, biochemistry and serological results of all the participants.

Safety parameters: Safety parameters include laboratory and other vital check-ups for all the participants.

Efficacy parameters: Efficacy details of the IMP and significant changes with the comparator drug.

Comments: Additional information about the completed milestone.

Adverse Events: Two types of adverse event data are to be reported

• Serious Adverse Events: A table of all anticipated and unanticipated serious adverse events, grouped by organ system, with number and frequency of such events in each arm of the clinical trial.
• Other (Not Including Serious) Adverse Events: A table of anticipated and unanticipated events that exceed a frequency threshold within any arm of the clinical trial, grouped by organ system, with number and frequency of such events in each arm of the clinical trial.

Details of Serious Adverse Event (per arm/group): Overall number of participants affected by one or more Serious Adverse Events.

Overall Limitations and Caveats: If appropriate, describe significant limitations of the trial.

CLINICAL TRIAL REGISTRATION PROCESS:
The sponsor of clinical trial or principal investigator is responsible for conducting the trial and has the right to publish results of the trial.

• A sponsor-investigator means an individual who both initiates and actually conducts a clinical investigation under them the test article is administered or dispensed involving, a subject.
• Data providers use a web-based data entry system called the Protocol Registration and Results System (PRS) to register clinical studies and to submit results information for registered studies.
• Before applying for a PRS account, one should ensure that the appropriate individual has submitted clinical study information to ClinicalTrials.gov.
• Protocol information must be clear and informative. It must be consistent with the ClinicalTrials.gov Protocol Data Element Definitions.

Content Courtesy: ClinicalTrials.gov

The major concern is how well a consultant analyses the Regulatory Compliance obligations and values the company’s needs.Here are some of the common parameters that, in principle, help a company measure the credibility and derive value out of its consultative engagement.

• Follow mandatory processes like development, preparation, assembly and submission of technical documentation for the purpose of marketing authorization applications
• Meet requirements of regulated, semi regulated and non-regulated standards
• Understand all centralized, decentralized, national and mutual recognition procedures
• Handle all pre-submission activities, including the orphan drug designation
• Compile all types of drug submissions like NDS, NDA, BLA and MAA
• Convert paper or non-eCTD electronic submissions (NeeS) documents into electronic form through upgraded eCTD software
• Communicate with the Regulatory authorities and acknowledge comment letters, assessment reports and quality control reports within stipulated time
• Organize scientific advice meetings with Regulatory agencies for smooth drug development process
• Follow the European Clinical Trial Authorization (CTA) and ethics committee applications submission protocols
• Provide diligent data evaluations and risk management plan
• Evaluate and effectively handle change controls for EU and other regions

There are other critical areas that will demand your attention during a compliance life cycle. And, if you find yourself asking all the questions but getting no definitive solution roadmap, it’s time to look for a partner who brings the experience, the expertise and, more importantly, who brings value to you!

GLOBAL REGULATORY AFFAIRS CONSULTING MARKET OVERVIEW
Biopharmaceutical industries are highly synchronized by various regulatory authorities across the globe. It is learnt that for the protection of public health, medical devices and pharmaceutical products are subject to strict regulations. Pharmaceutical companies are planning to outsource their regulatory affairs operations to various competent contract research organizations (CROs) and contract manufacturing organizations (CMOs) to secure approval. CRO’s offer definitive cost efficiencies, process improvement and utilization of the expertise which helps in the growth of the regulatory affairs outsourcing market.

In 2013, the regulatory writing and publishing services segment reportedly took 40% share out of the total regulatory affairs outsourcing market owing to growing need for rapid approval and submission of drug applications. In addition, the understanding of global and domestic regulatory requirements by regulatory writers helps in driving the growth of the regulatory writing and publishing services market.

It is reported that during 2014 to 2020, the regulatory consulting and legal representation services segment is estimated to have the fastest growth rate in the regulatory affairs outsourcing market. This is owing to growing pressure for regulatory consulting and increasing need of client interaction with various regulatory agencies.

The global regulatory affairs outsourcing market is segmented by services into regulatory affairs; clinical trial applications and product registrations; regulatory writing and publishing; regulatory consulting and legal representation; and others (post approval maintenance, reimbursement consulting etc.).

In 2013, the regulatory writing and publishing services segment reportedly took 40% share out of the total regulatory affairs outsourcing market and is expected to maintain its lead during the forecast period through 2014 to 2020. Increasing need for user/reviewer friendly and complete drug application submissions and sound knowledge for drug development services are some of the factors which have contributed towards the large market size of the regulatory writing and publishing services. Furthermore a well-written clinical study report (CSR) adds a lot of value in the final production of clinical trial documentation, which is in compliance with stringent regulatory requirements of the drug development process.

It is also stated that the regulatory consulting and legal representation services segment is expected to increase at a compound annual growth rate (CAGR) of above 14% owing to growing demand of drug manufacturing companies for product safety and efficacy evaluations. In addition, growth of the regulatory consulting and legal representation services segment can be increased if pharmaceutical companies try and minimize business impacts such as product recalls and loss of sales ensuring global environmental compliance.

In 2013, North America took the largest market share for the global regulatory affairs outsourcing market owing to increased number of clinical trial activities, vast presence of research units and cost benefits incurred by shifting high costs of in-house resources for various regulatory activities. Asia Pacific is predicted to have the highest growth rate over the forecast period that is attributed to availability of large population base and skilled workforce. Over the next few years, there is scope of increased contract manufacturing activities in emerging nations such as China, India, Malaysia and Vietnam which will give rise to growth of the global regulatory affairs outsourcing market in Asia Pacific region.

• Develop and manage client’s Company Core Data Sheet (CCDS)
• Deploy a technology solution for management of CCDS by leveraging the “OpenText” platform
• Manage client’s global labeling management activities
• Leverage strong industry knowledge and expertise supporting further enhancement of global competitiveness and reduce operating costs

• Over 60% Savings on Cost of Compliance
• Established and Streamlined Master Dossier Management Process

BUSINESS IMPERATIVES

24 CMC Variations (amendments) for established medicinal product for treatment of hemorrhoids and other related anorectal conditions in 12 African countries.

CHALLENGES

• Coordination across local markets
• Distributed country specific source documents
• Coordination with the proposed drug product manufacturing sites
• Country specific publishing requirements

FREYR SOLUTIONS & SERVICES

• Harmonizing country-specific dossiers for 12 African countries
• GAP Analysis
  • Assessment of dossiers across all countries
  • Assessment and remediation of gaps between current drug product manufacturing and the proposed drug product manufacturing changes
• Master Dossier Creation for Module 2 & 3
• Country Variation
• Country specific variations from master dossier – Applications forms, cover letters and GMP documentation from respective Module 1

CLIENT BENEFITS

• Cost savings of 60% and upwards
• Established streamlined process for managing future change controls impacting the African countries

• Successfully completed 4 Clinical Study Reports (CSR)
• Zero defect & zero correction cycle, high quality delivery
• Fastest turnaround time of 30 days

BUSINESS IMPERATIVES

• The agency carried out Phase 1  with Influenza Antiviral DAS 181-F04
• Freyr supported the client with CSR publishing services
• The project served in completion of publishing 4 CSR’s. Each CSR contained 5k pages and two resources completed the project within 30 days

CHALLENGES

• Conversion of documents from word to PDF was not carried out properly resulting in many unwanted spaces
• As individual documents were shared Freyr had to merge which resulted in generation of inconsistent new page numbers
• Large number of documents in different format had been shared
• Frequent updates  to shared documents resulted in republishing

FREYR SOLUTION & SERVICES

• Performed document level QC ensuring all details are accurate and are 100% submission ready
• Under submission level publishing, Freyr made sure all documents are in accordance with regulations of USFDA
• Published CSR, validated and submitted CSR successfully with zero correction cycle

CLIENT BENEFITS

• Quick turnaround saved considerable amount of cost and time
• Freyr customized QC and QA process to ensure accurate end product
• Expert team quickly adapted to last minute changes made by client
• Assured high quality CSR documents