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Epidemiological Study Design

Epidemiological studies classified based on distribution of disease:

1. Descriptive Epidemiological study:

Describe the distribution of disease or condition in human population

Eg.distribution of certain condition or disease in a certain population in relation to age, sex or other characteristics

2. Analytical Epidemiological Study:

These studies Test the hypothesis.

Looks for association based on;

1. Groups or individuals eg: Correlation study, trend study
2. Based on individuals eg: Cross – sectional, cohort, case control study

Cohort Study: Identification of individual forming a group with certain exposure and the group is followed up in time to ascertain the disease occurrence.

Case Control Study: Case control study directed at the prior exposure of the disease, which caused the disease and thus proceed from effect to cause.

Cross Sectional Study: The study is conducted to collect data on both exposure and outcome individuals of study population.

 Epidemiological Studies classified based on the role and control of investigator on the study:

1. Observational Study: Investigator observes the occurrence of condition or disease in population with certain exposure. These studies are most feasible and practical to conduct.
2. Experimental Study: Investigator controls the assignment of exposure, associated factors and observation of the outcome. These are robust study design to test hypothesis.

Epidemiological studies classified based on direction of investigation.

1. Prospective study: Population exposed or non exposed to disease are followed up and compared with the respect to subsequent development of disease or the outcome of the study.
2. Retrospective study: Populations with exposed or non exposed disease are compared to determine whether they differ in past exposure to the causative factor which is the study hypothesis.
3. Ambispective study: Study is both retrospective and prospective. One or more variable are measured retrospective and the other one retrospective, or variables primary variable is measured both retrospective and prospectively.
4. Non – Directional study: Investigator observes exposure and disease status simultaneously in a study population.
5. Retrolective study: Data collected before the study design, not necessarily for the study purpose.
6. Prolective study: Data collected after study design for the study purpose.

 

Randomization and Blinding in Clinical Research

Randomization in clinical research is assignment of the study subjects to either a treatment group or a control group by an element of chance to reduce bias.

Simple randomization – Study subjects are randomly assigned to treatment group or a control group by single sequence. Most common method of simple randomization is flip of coin. Other methods include computer generated random list, deck of card, use of dice for patient allocation to the groups. Simple randomization is designed in large clinical research.

Block randomization – Study subjects randomized into blocks that result in equal sample size, which ensures balance in sample size across groups over time. Blocks are randomly chosen to determine subject assignment into the groups. Block randomization design is used to balance sample size and covariates.

Stratified randomization – Stratified randomization is created by separate blocks for each combination of covariates, and subjects are assigned to appropriate blocks of covariates and then simple randomization is performed within each block to assign subjects to one of the groups. Stratified randomization is designed to balance the influence of covariates.

Blinding in clinical research is, one or more parties are kept unaware of treatment assignment.

Single Blind Study – Study Subject is kept unaware of treatment assignment.

Double blind Study– Study subject and investigator are kept unaware of treatment assignment.

Triple Blind Study – Study subject, investigator and data analyst are kept unaware of treatment assignment.

Roles and Responsibilities of Clinical Research Coordinator (CRC)

• Facilitates and coordinates the daily clinical trial activities and plays a critical role in the conduct of the study.
• Schedules study subject appointments and serves as the patient liaison to the PI and other participating physicians.
• Reviews and comprehends each assigned protocol including study proceedings and timelines.
• Working closely with the PI, CRC participates in an integral way in the informed consent process by communicating clearly with potential study subjects about protocol. Possesses a thorough knowledge of the informed consent process as well as a thorough understanding of the study protocol in order to be able to answer all questions pertaining to the study posed during the informed consent process.
• Coordinates approval of new study agreements and contracts.
• Coordinates and attends sponsor Site Selection visits, Routine monitoring visits, and study close out visits.
• Completes case report forms. Extracts data from patient file (Source documents) in a timely manner.
• Responds to data clarification requests in a timely manner.
• May attend Investigator meetings requiring travel and report pertinent information back to research team members.
• Coordinates with PIs and department to help ensure that clinical research and related activities are performed in accordance with protocol, SOP, GCP and applicable regulatory requirement
• Assists the PI in development of materials and tools necessary to appropriately train individuals involved in the conduct of the study, like study protocol requirements, schedule of visits, execution of research plan. Maintains records and other documentation of training.
• Maintains subject screening logs and protocol deviation logs.
• Maintains a excel sheet, tracking updates to database of all subjects enrolled on clinical trials.
• Coordinates and facilitates monitoring and auditing visits. Notifies appropriate institutional officials of external audits.
• Collaborates with PI and institution to respond to any audit findings and implement-approved recommendations.
• Completes documentation on each study visit that is used to track all study related activities so that time, effort and materials can be accounted for on a monthly basis.
• Ensures that all materials for each clinical trial protocol are available for subject enrollment.
• Works collaboratively with the other members of the clinical research team and the clinical and administrative support teams to ensure protocols are followed and that there is timely documentation and submission of study data.
• Performs specimen processing and shipment of biological specimen duties.
• Assists with development of study materials including but not limited to, the informed consent document, case report forms (CRFs), enrollment logs, and drug/device accountability logs.
• Establishes and organizes study files, including but not limited to, regulatory binders, study specific source documentation and other materials as required.
• Assists the Principal Investigator in submission of accurate and timely closeout documents to applicable IRB/IEC and applicable regulatory requirement.
• Arranges secure storage of study documents that will be maintained according to institutional policy or for the contracted length of time, whichever is longer.
• Promotes the ethical conduct of research by reporting good faith suspicions of misconduct in research.

Clinical Research Industry – Stakeholders/ KeyPlayers

Clinical Research industry is a dynamic and interdependent industry. The industry works in collaboration with various organizations. The stakeholders of clinical research industry are subjects, sponsor, investigator and team, government agencies, Regulatory authorities, monitor, Institutional review board, Contract research organization, Independent ethics committee, Academic institutions, public and private sectors whose contribution significantly influence the clinical research process.

All Stakeholders are bounded by three basic responsibilities –  Ethical, Scientific and Administrative Responsibilities.

Sponsors are primary stakeholders who intiates, organizes, finances clinical research. Sponsors can be an individual or company or an organization. Usually, Sponsors are pharmaceutical company, biotechnology companies, Academic Institutions.

Investigator and investigator team is appointed/hired by sponsor. The Investigator team is constituted by co-investigator, sub-investigator, clinical research coordinator, study nurse, pharmacist, laboratory personnel, research assistant and subject recruiter. All team members should be qualified, experienced and trained to conduct assigned clinical research duties under supervision of principal investigator. Clinical Research should be conducted in accordance with ethical principles that have their origin in declaration of Helsinki and consistent with good clinical practice, standard operating procedures and Applicable Regulatory Requirements.

Regulatory Authorities are the stakeholders responsible for giving permission to conduct clinical research in the country. The sponsor submits the investigational new drug application or new drug application to the regulatory authorities for review and approval. Once the sponsor obtains approval to initiate and continue the research, regulatory authorities conduct audits and inspection upon serious non compliance, major violations. Regulatory Authorities are also responsible for ensuring protection of public health by safeguarding rights, safety and wellbeing of trial subjects

Institutional review board or independent ethics committee is stakeholder at the clinical research site. Trial should be initiated at the site only after approval from the ethics committee. Ethics committee is responsible for protecting rights safety and well being of trial subjects, Review of ongoing clinical trials, compensation and payments to trial subjects.

 

 

 

Clinical Research Associate (CRA)

Clinical Research Associate also known as monitor is employed by either a pharmaceutical company or a contract research organization (CRO) which works on behalf of pharmaceutical companies. Clinical trials may be carried out at various phases, trials on patients with a disease, and studies conducted after the launch of a new drug to monitor safety and side effects. The CRA will be involved in all stages of the clinical trial, including identifying an investigation site and setting up, initiating, monitoring and closing the trial upon completion or termination.

Roles and Responsibilities of CRA:

• Identifying/selecting an investigator who will be responsible for the conduct of the trial at the trial site.
• Liaising with doctors/consultants or investigators on conducting the trial.
• Setting up the trial sites, which includes ensuring each centre has the trial materials, including the trial drug often known as the investigational medicinal product. Training the study staff in standard operating procedure for the clinical trials as per applicable regulatory requirements.
• Verify that investigator and investigator’s team are adequately trained and comply with the protocol.
• Verify that IRB/IEC operates and complies as per GCP, SOP and applicable regulatory requirements.
• Monitoring the trial throughout specified duration involving monitoring visit to the trial sites.
• Source data verification
• Informed consent form review, case report form review, investigational drug accountability, and adverse event review.
• Ensuring all unused trial supplies are accounted for.
• Writing visit reports, filing and collecting trial documentation and reports.

Skills:

Skills required for CRA job profile are,

• Excellent communication skills (both written and oral) and the ability to build effective relationships with trial centre staff and colleagues
• The ability to motivate others
• An eye for detail
• Ability to multi-task and think on your feet
• Good organizational, IT and administrative skills – job involves lot of documentation and recording of information through computerized processes such as clinical trial management systems and electronic data capture.

 Prospects:

Depending on experience in the fields of health-care and clinical research as well as areas of interest, CRAs can aspire to be

Lead CRA.

Head of Clinical Research.

Project Manager.

Director of Clinical Operations.

The work of a Clinical-Research Associate opens career opportunities in the pharmaceutical research-and-development sector for positions in pharmacovigilance, regulatory affairs, and marketing.

 

 

 

 

 

 

 

 

 

 

TYPES OF CLINICAL TRIALS /RESEARCH/STUDY

Categorized according to objective of clinical research:

Treatment Trial also known as interventional trials test experimental treatments, new combinations of drugs, or new approaches to surgery or radiology/radiation therapy, psychotherapy which are not officially approved.

Prevention Trial looks for better ways to prevent developing disease in people who have never had them or prevent them from returning. Eg: Vitamins, vaccines, minerals, lifestyle changes

Diagnostic Trial conducted to find better tests or procedures for diagnosing a particular disease or condition.

Screening Trial tests the best way to detect certain diseases or health conditions.

Quality of Life explores ways to improve comfort and the quality of life for individuals with chronic illness.

Genetic Studies aim to foresee the genetic makeup of individual and anticipating chances of developing disease associated with it. Genetic studies may help in developing tailor made treatments.

Epidemiological Studies are performed to identify the disease pattern, causes effects of health and disease in a predetermined population. Epidemiological studies are pivotal in public health, making health care policies and evidence based medical practise by identifying risk factors and preventing the disease.

Categorized as therapeutic and non therapeutic trials:

Therapeutic Trial the treatment being investigated is likely to benefit the trial subject.

Non therapeutic Trial aims at obtaining knowledge and information about the product, which may contribute to the development of drug. Non-Therapeutic trials are less likely to directly benefit the trial subject.

Categorized based on study design:

Single Centre: Study conducted at one location.

Multi- Centre: Study conducted at several locations, different locations within the state or different location in different countries.

Randomized Clinical: Study subject are randomly assigned to treatment group or control group by element of chance.

Open Labelled :Subject and Investigator (Researcher) are aware of drug being given.

Blind: Subject is unaware of treatment assignment i.e, treatment group or a control group.

Double Blind: Subject and investigator are unaware of treatment assignment i.e, treatment group or a control group.

Placebo controlled: The medicine like substance which does not contain active ingredient as that of treatment drug.

Add-on:  Subjects receive existing treatment; few of the subjects receive add-on treatment while others are not given treatment drug or given a placebo.

 

 

Clinical Research Coordinator

A clinical research coordinator (CRC) also known as study coordinator (SC) or simply ‘research coordinator’ is one of the most important people at a clinical research site and plays a very vital role in the conduct of a clinical trial. A good CRC with good understanding of the clinical trial processes, guidelines and regulations is a huge advantage to clinical trial site.

A CRC is the person who is regularly in touch with clinical trial subjects and conducts most of the study related activities and documentation as delegated to him/her by the principal investigator. A CRC is a link between the sponsor / CRO, investigator site and the ethics committee.

Thus, this job profile demands high competency and knowledge of clinical research. In order to start your career as a good CRC, having completed a course in clinical research will be a great advantage.

Skills:

Following are the Skills Required for CRC job Profile;

• excellent communication skills (both written and oral) and the ability to build effective relationships with trial centre staff and colleagues
• the ability to motivate others
•  an eye for detail
• the ability to multi-task and think on your feet
• Good organizational, IT and administrative skills – the job involves documentation and recording of information through computerised processes such as clinical trial management systems and electronic data capture.

Prospects:

Depending on experience in the fields of health-care and clinical research as well as areas of interest, CRCs can aspire to become CRA.

CRAs can aspire to, among other positions, the following:

• Lead CRA.
• Head of Clinical Research.
• Project Manager.
• Director of Clinical Operations.

The work of a Clinical-Research Associate opens career opportunities in the pharmaceutical research-and-development sector for positions in pharmacovigilance, regulatory affairs and Medical Writing.

 

 

Clinical Research/trial/study is evaluation of safety and efficacy of drugs in human beings

Clinical research is conducted only after approval/permission from the regulatory authority of the country and Institutional Review board/Independent Ethics Committee /Ethics committee approval at the site.

Phases of clinical trial

Phase 1 – human pharmacology phase

Phase 2 – therapeutic exploratory phase

Phase 3 – therapeutic confirmatory phase

Phase 4 – Post marketing surveillance

 

Ethics in Clinical Trials

Protection of rights, safety and wellbeing of trial subject is the most important consideration in the clinical research industry. It is responsibility of all the stakeholders to safeguard study subjects.

Clinical trial should be conducted in accordance to ethical principles that have their origin in declaration of Helsinki and consistent with protocol, International conference on Harmonization – Good Clinical Practices (ICH –GCP), Standard Operating Procedure (SOP) and Applicable Regulatory requirements.

 

Informed Consent in clinical trials

Informed consent is subject willingness to participate in the clinical trial. As per ICH-GCP principles, informed consent should be obtained prior to subject participation in the trial. Trial Subject should not be forced or pressurized to be part of clinical trial. Trial subject has the right to participate or stop continuing to be part of study at any given point of time during the conduct of clinical trial.

Investigator is responsible for informed consent process. Investigator and Subject sign informed consent document once patient is willing to participate in the trial.

 

Clinical Research – Job Opportunity

Clinical Research Coordinator

Clinical Research Associate

Drug Safety Associates, Senior Drug safety associates, Medical Reviewer (Doctors) Team Lead, Project Manager (Pharmacovigilance)

Data Entry Associates, Senior Data Entry Associate, Data Analyst, Data manger (Clinical Data Management)

Medical Writer, Regulatory writer