A day in the life of a CRA

Hi, I am Gangichatti Laxman Kumar & I work as Clinical Research Associate with Veeda and this is how a day in my life looks like

Although I’m based out of Hyderabad, I might be visiting a site that’s in a completely different part of the country by the time you’ll read it. This blog is supposed to walk you through a typical day in the life of a CRA.

A Clinical Research Associate plays a crucial role within the pharmaceutical businesses. A CRA is responsible for pre study qualification visits, reviewing the study progress, checking the quality & accuracy of data collection, compliance of patients to trial visits, and will ensure good clinical practices are maintained throughout the trial

After successfully completing Pharma-D, I started working as a Safety Associate to the regulatory bodies, after that I switched to clinical research operations and started working as a CRA in Oncology, NeurologyEndocrinology, Cardiology and General Medicine. I have also worked in the department of BA/BE trials where I experienced a multi-functioning team and finally moved to Veeda Clinical Research where I got the opportunity to work in BA/BE studies as well as Late Phase Trials in the field of Oncology.

Being a CRA, I have to spend a significant amount of time traveling to and fro to all the research sites that I have been assigned with which are spread throughout the country, I visit 4 to 5 sites in a day.The very fact that I have to be constantly on the move, which happens to be a part of my job, adds a travel aspect into the mix that always remains fresh.

I believe Social interaction plays an important role in learning and with this role I get to interact with a lot of people,from site coordinators to doctors to project managers, which has proven to be quite effective in my cognitive learning.

My standard operating day comprises of monitoring and supervising data files as a part of source data verification process to ensure that the site is entering data accurately and in a timely manner.The safety of a patient is of the utmost importance at Veeda and I, along with my staff, regularly assess patient notes to ensure safe undertaking of procedures as per the protocol.

Every role comes with its own set of challenges and the role of a CRA is no different. Veeda offers workplace flexibility, which helps me deal with challenges calmly & efficiently. Being a CRA, I practice a fast-paced lifestyle but for me, the sense of accomplishment I get from tackling all those challenges is what makes me choose this line of profession every time.

INTRODUCTION

In our last blog on Master protocols, we discussed the definition of master protocol, the types and advantages of using Master Protocol in clinical trials. In today’s article, we will like to present before you the parameters that are kept in consideration while designing a master protocol for oncology drugs and biologics. During the preparation of master protocols, different parameters are kept in consideration like:

  • Specific Design Considerations
  • Biomarker Development Considerations
  • Statistical Considerations
  • Safety Considerations
  • Regulatory Considerations

SPECIFIC DESIGN CONSIDERATIONS IN MASTER PROTOCOLS

  1. Use of a single common control arm

FDA recommends the use of a single control arm with the current System Organ Class (SOC) while developing a master protocol where multiple drugs are assessed in a single disease.SOC for the target population can be changed during the conduct of the trial if there is a new drug approval or scientific evidence that makes it unethical to randomize patients based on the previous SOC. During such a situation, FDA recommends the sponsor to suspend patient enrollment until the protocol, the SAP, and the protocol informed consent document are modified to include the new SOC as control.

  1. Novel combination of two or more investigational drug

While writing a master protocol, where two or more investigational drugs are involved as a combinational product, the sponsor should summarize the following.

  • Safety of the combinational product
  • Pharmacology of the combinational product
  • Preliminary efficacy data for each investigational drug
  • Rationale for the use of the drugs as a combination product
  • Evidence of any synergistic effect (if any) of the two or more investigational drugs when given in combination.

The FDA strongly recommends that the sponsor ensure that the Recommended Phase II Dose (RP2D) for each drug having antitumor activity should be identified in all cases.

  1. Studies with drugs targeting multiple Biomarkers

Early discussion of biomarker research strategies is highly encouraged by the FDA when the sponsor plans to use one or more biomarkers to guide patient preference for trials. A defined plan for the allocation of eligible patients should be present. Patient selection studies must be analytically checked with well-defined parameters for master protocols involving drugs that target multiple biomarkers.

  1. Adding and stopping treatment arms

Before beginning the trial, the sponsor should make sure that the master protocol and its corresponding SAP identify conditions that would contribute to adaptations, such as introducing a new experimental arm or arms to the study, re-estimating the sample size based on the interim analysis results, or discontinuing the experimental arm on the rules of futility.

  1. Independent Data Monitoring Committee (IDMC)

The master protocol should provide the details of the IDMC that is involved in monitoring the efficacy results and the details of Independent Safety Assessment Committee (ISAC) that is involved in monitoring the safety results. However, the IDMC can perform both the functions of safety and efficacy. For marketing an oncology drug, if the basis of marketing application involves one or more sub studies, FDA recommends the inclusion of independent radiologic review committee to perform blinded tumor-based assessments.

BIOMARKER DEVELOPMENT CONSIDERATIONS

            Master protocols assessing biomarker-defined populations should explain the rationale behind the use of that particular biomarker.The sponsor should employ in vitro diagnostic (IVD) tests that are analytically validated, establish procedures for sample acquisition, handling, and the testing and analysis plans as early as possible. The sponsor may need to submit the IVD’s analytical validation data for FDA(CDRH or CBER) to determine whether the clinical results will be interpretable.

STATISTICAL CONSIDERATIONS

If a sponsor introduces randomization into the design of an umbrella trial, the FDA advises that a standard control arm to be used where possible.Bayesian statistical method or other methods for dropping an arm, modifying sample size, or implementing other adaptive strategies can be used in preparation of master protocols. The SAP should include details on implementation of Bayesian or other methods as described in the FDA guidance for industry Adaptive Design Clinical Trials for Drugs and Biologics and the guidance on Enrichment Strategies for Clinical Trials to Support Approval of Human Drugs and Biological Products.Statistical considerations for master protocols can be strategized in four different ways:

  1. Nonrandomized, Activity-Estimating Design
  2. Randomized Designs
  3. Master Protocols Employing Adaptive/Bayesian Design
  4. Master Protocols With Biomarker-Defined Subgroups

SAFETY CONSIDERATIONS

The sponsor should implement a structured team of ISAC or an IDMC to assess the safety as well as the efficacy of all master protocols.The constitution of this committee and the definition of its responsibilities should be well defined in the IND. A sponsor should not begin a clinical trial until the master protocol has been reviewed and approved by an IRB or IEC. The FDA encourages the use of a central IRB to promote the IRB analysis of master protocols. The sponsor is required to perform a safety review of master protocols more regularly than on an annual basis and supply the investigator with the details.If the master protocol contains proposals to include pediatric patients in the study, the FDA advises that the IRB include a pediatric oncology expert in its team who has expertise with the regulatory criteria for the enrollment of pediatric patients in clinical investigations, including parental approval and consent. The informed consent document should be submitted to the IRB for review.

ADDITIONAL REGULATORY CONSIDERATIONS

Each master protocol should be submitted as a new IND to the FDA. This is done to avoid miscommunication owing to the sophistication of master protocols that may hamper patient safety.If the sponsor is conducting a clinical trial on more than one indication for oncology drugs or biologics, the IND should then be forwarded to the Office of Hematology and Oncology Products at CDER or CBER for approval.

REFERENCE

Master Protocols: Efficient Clinical Trial Design Strategies to Expedite Development of Oncology Drugs and Biologics, Guidance for Industry, Draft Guidance.U.S. Department of Health and Human Services, Food and Drug Administration, September 2018.

With many new therapeutics approved annually, the demand for biologics has seen exponential growth in the pharmaceutical market. In the bioanalytical community, the study of large molecules is now a hot topic of discussion. The snowballing importance of peptides and proteins as therapeutic agents,combined with the colossalopportunities offered by new MS-based technology, has unlocked a new world for bioanalytical scientists.

Ligand-binding assays (LBAs) such as enzyme-linked immunosorbent assays (ELISA) or UV identification of individual peptides using high performance liquid chromatography (HPLC) are the standard methods for quantification of biologic drugs.However, these methods are typically expensive, time-consuming to develop, and havelimited selectivity and antibody cross-reactivity. This results in a lack of interference specificity and high background levels that are not appropriate for fulfilling the specifications of the biopharmaceutical industry to identify different proteins and peptides with increasing sensitivity and reproducibility.

Liquid chromatography combined with tandem mass spectrometry (LC-MS-MS) has been widely used for small molecule bioanalysis in pharmaceutical laboratories since the 1980s. As like smaller molecules, LC-MS-MS also carry advantages for biologics:

  • It is not susceptible to cross-reactivity of the antibody because LC-MS-MS involves direct assessment of the analyte’s chemical properties.

 

  • It provides excellent selectivity, being able to discern and quantify extremely homologous isoforms with precision and accuracy over a large linear dynamic range, even at low levels.

 

 

  • Due to its high analytical sensitivity and selectivity, in addition to high-throughput capability, LC-MS/MS has been considered the primary technique to measure the concentrations of the first generation and second generation antipsychotics in schizophrenia patients.

Mass spectroscopy has gained increased interest for peptide and protein analysis over LBA because:

  • LBA detects molecules based on binding affinity and 3D conformational structure but they may not be able to distinguish between a protein and its metabolites.
  • In contrast with LBA, MS-based approaches have a potential and would be able to produce more precise data on unchanged peptide/protein levels, in situations where metabolism hampers reliable LBA data.
  • MS techniques usually offer absolute concentrations of medications. This can depend on the form of an assay for LBA methods, and they may provide either absolute or free concentration of drugs.

However, LC-MS-MS-based bioanalysis for large molecule drugs poses a range of new obstacles like difficulties in sample processing and extraction measures for quantification of large molecules. The reasons include:

  • The background peptides and proteins in the biological matrices compete with the biotherapeutic molecule of interest, creating interferenceproblems and impacting accuracy.
  • The lack of significant evidence during quantification arises for being unable to catch free drugs that may circulate in serum.

Recently, many LC-MS-MS technological advancements have been made that can help solve all of these concerns. In particular, the increase of ionization efficiency and ion transmission in recent triple quadrupole instruments has greatly enhanced sensitivity, allowing biologics to be detected at picogram or sub-femtogram levels.

 

Advances in technologies inside the LC-MS-MS include improved ion collision focusing, which brings more ions to the detector, as well as upgrades to the dynamic range of the detector, to increase bioanalysis sensitivity and efficiency. Recently, there has been a growing interest in integrating LBA immunoaffinity enrichment with LC-MS-MS quantification to integrate LBAs with the sensitivity and selectivity of LC-MS-MS technologies with greater precision and wider immune capture capabilities.

Automated Column-switching LC–MS/MS, Microextraction packed sorbent (MEPS)/LC-MS/MS, and Disposable Pipette extraction (DPX)/LC-MS/MS are some of the recent techniques that have been used to quantify large molecules.

Two major methods are widely used when using LC-MS/MS based technologies for the bioanalysis of large molecules:

  1. Intact analyte LC–MS(/MS) approach

This approach is predominantly used for peptides, small proteins and oligonucleotides with a molecular weight typically below 4–8 kDa.

 

  1. LC–MS/MS approach using a digestion step

This approach is more complex and mainly used for proteins or larger peptides. This approach involves a (enzymatic) digestion step in addition to the intact analyte approach, where the protein/peptide is digested into smaller peptides.

Today, it is most common to use traditional LC-MS/MS triple quadrupole instruments for quantification for both the intact and the digested analyte approaches. According to the existing standards, 4-6-15 (four out of six QC samples should be within 15% of the nominal value) is used as an approval criterion for large molecular LC-MS/MS assays. 4-6-20 approval requirements are proposed for larger intact analytes, in particular, if a hybrid LC-MS/MS approach is used. A labeled peptide for peptide analysis or either a labeled intact protein or a labeled signature peptide can be used as an Internal Standard (IS) to establish a successful LC-MS/MS method

Several guideline documents have been issued by the ICH and FDA to help standardize large molecule bioanalysis studies. These recommendations can be found on the website of the appropriate regulatory agency. While LC-MS-MS technologies have progressed to be more appropriate for biological bioanalysis, for non-experts who need to create and measure new biologics, the variety of mass spectrometry technologies and techniques, sample preparation methods, and reagents could be overwhelming.The new advances in instrumentation and software will bring substantial changes in the consistency and efficiency of bioanalysis tests, providing more accurate and compliant results with significant patient safety consequences.

REFERENCES

  1. Suma Ramagiri, Trends in Bioanalysis Using LC–MS–MS. The Column,The Column-12-07-2015,Volume 11,Issue 22.
  2. Magnus Knutsson, Ronald Schmidt & Philip Timmerman, LC–MS/MS of large molecules in a regulated bioanalyticalenvironment – which acceptance criteria to apply? Future Science, BIOANALYSIS VOL. 5, NO. 18, https://doi.org/10.4155/bio.13.193

Will BREXIT have any impact on CROs?

Introduction

The United Kingdom comprises of England, Scotland, Wales, and Northern Ireland. It is an island nation in northwestern Europe. The exit of the United Kingdom from European Union to become a ‘third country’on February 1, 2020 is termed as Brexit. The withdrawal agreement that provided a transition period of one year came to an end on December 31, 2020.Thus, the Medicines and Healthcare Products Regulatory Agency (MHRA) has been the UK’s independent authority for medicines and medical devices since January 1, 2021. The Brexit will have both direct and indirect effect on the future of UK and EU clinical trials. The impact of Brexit on pharmaceutical companies will be seen at the levels of regulatory alignment with respect to the forthcoming implementation of the EU Clinical Trial Regulation (EU CTR).As the best universities for research in the study of clinical, pre-clinical, and medicine are present in the UK with strong regulatory and IP safety structures, the United Kingdom has become globally a major centre for the pharmaceutical industry. In addition, most generic pharmaceutical companies are registered with a UK address. The departure from the EU would thus lead to hectic structural shifts, with a huge amount of time and investment on both sides.

Impact of Brexit on Outsourcing of Clinical Trial

Till now, many pharmaceutical companies based out of Europe were outsourcing their projects to contract research organizations (CROs) and contract manufacturing organizations (CMOs) based in the UK. Post Brexit, these scenarios may change. As of now, the European Commission has given its decision that the UK authorities will have partial access to Article 57 and will also have partial access to EudraVigilance database.

Because of Brexit, CROs and CMOs located in the United Kingdom are no longer members of the EU, and this will have a dramatic impact on the European portion of the clinical trials for delivery of investigational medicinal products (IMPs).The effect of clinical trials on the supply chain post Brexit will totally disrupt the new drug development process due to major negative financial and economic effects. Brexit can influence the clinical trial and drug discovery scenario that may involve access to drugs and Investigational Medicinal Products (IMPs), results, financing and the workforce of clinical trials.

For BE studies carried out in EU, the reference product can be made to a RefMP (UK Reference product) that has been granted in the Union in accordance with Articles 8(3), 10a, 10b or 10c of Directive 2001/83/EC. It is important to understand for the sponsor and the CRO that bioequivalence studies conducted with a medicinal product sourced in the UK can be used by EMA if the new MA using those BE studies have been granted before January 31, 2020.

Conclusion

United Kingdom is the 2nd destination of Indian Pharmaceutical exports after USA.  Some CROs have internal Brexit Task Force comprised of talented individuals who very well know their roles and responsibilities. CROs are preparing themselves to engage and capitalize the new regulatory process in the UK and EU so as to avoid costly delays and disruptions of clinical trials. However, many questions still remain unanswered. One of the biggest issues refers to complaints regarding the shipping of materials from the UK to the EU for clinical trials. Will the volunteers involved be at any risk? Or will international boundaries lead to delay in clinical trials and difficulty in site management? Or will there be any imposition of tariffs that could lead to disinterest among pharmaceutical sponsors in the UK in carrying out clinical research? Thus, it will be interesting to see what is in store for the CROs post BREXIT. However, because the UK and the EU account for less than 15-18 percent of total Indian pharmaceutical revenues, BREXIT is expected to have a little impact on Indian pharmaceutical firms.

References

  1. The Landscape for CROs post Brexit: An Update. Accessed at

https://dwlanguages.com/2018/02/22/cros-post-brexit/

  1. Brexit Solutions, Clinigen Clinical Supplies and Management. Accessed at

https://www.clinigencsm.com/brexit-solutions

  1. Questions and answers to Stakeholders on the implementation of the Protocol on Ireland/Northern Ireland, 11 December, 2020. European Medicine Agency (EMA/520875/2020)
  2. Future of clinical trials after Brexit.Cancer Research UK, School of International Futures (SOIF).

The role of ADME in Phase 1 Clinical Trials

Introduction

The drug development process for pharmaceuticals and biologics is strictly regulated across the globe by different regulatory authorities.

The process of drug development comprises of following stages

Stage 1:- Target and lead identification, in-vitro testing of tissues, plasma, etc. for bench testing of the product.

Stage 2:- Non-clinical testing in live animals (in-vivo testing).

Stage 3:- Filing of IND (Investigational new drug) to get approval to test on humans. If approved, the clinical trial begins with Phase I clinical trials which are also known as first in human studies.

Stage 4:- Filing of NDA (New Drug Application) after successful Phase II trial completion. If approved, the clinical trial begins for Phase III.

Step 5:- Submission of the document to request approval to market the product after a successful Phase III clinical trial.

Phase I Clinical Trials

Phase I studies are designed to investigate the safety/ tolerability i.e. identifying Maximum Tolerable Dose (MTD), pharmacokinetics, and pharmacodynamics of an investigational drug in humans. Right Drug to the Right Patient with Right Dose at the Right Time is the ultimate goal or objective of Phase 1 Clinical Trials.

To achieve the objective of Phase I studies, scientists carry out studies in the following sections:-

  • • Clinical Pharmacology of the Drug

It involves studies like First-in-Human, SAD and MAD PK studies, Healthy vs Patient Population, ADME (Mass Balance), Specific population, Drug Interaction, Population PK, Biomarkers, Pharmacogenomics, and other special safety studies

  • • Exposure-response (PK/PD) of the drug

It involves dose selection and optimization, efficacy vs. safety, and clinical trial simulation.

  • • Biopharmaceutics of the Drug

It involves BA/BE and Food Effect studies

  • • Invitro studies carried out with the drug

It involves protein binding, Blood to Plasma Partitioning, Invitro drug metabolism, transport, and drug interactions.

  • • Bio-analytical methods

It involves validating assays and generating performance reports

  • • For Biologics, scientists carry out immunogenicity and comparability studies.

This article is all about the ADME studies involved in Phase 1 Clinical Trials.

What is Pharmacokinetics?

Pharmacokinetics is the study that involves the action of the human body on medicines. Absorption, Distribution, Metabolism, and Excretion are the major steps involved when a drug enters human body. Physicochemical properties of the drug, the administration route, intrinsic and extrinsic factors of the subject like diseases, organ dysfunction, concomitant medications, and food are the factors that affect the PK profile of an investigational drug.

Efficacy, Toxicity, Cmax, and Tmax are some of the important terms that we generally come across in PK studies.

ADME study is also known as mass balance study. ADME studies are important because it helps to determine other clinical investigations that might need to be conducted in support of regulatory approval for a new drug. The ADME is determined by attaching a radioactive isotope (radiolabel), such as carbon 14 (14C) or tritium (3H) to an investigational new drug and following the radiolabel in human subjects.

Human ADME studies are carried out by the sponsor to obtain valuable information about the investigational new drug which includes:

  • • Determining the routes of elimination and clearance mechanisms of the drug
  • • Identifying metabolites and determining the relative exposure of parent drug and metabolites
  • • Confirming that the human metabolite profile is covered by the metabolite profile in animals from toxicology studies

What is the type of study design carried out in ADME studies?

ADME studies are typically single-dose studies with healthy males (4-6 in numbers) at the intended route of administration.

What are the Primary and Secondary Outcome Measures Considered in an ADME study?

The primary outcome measures of ADME studies in Phase 1trials include

  • 1) PK Parameters

Maximum observed concentration (Cmax), time to reach maximum observed concentration (Tmax), area under the concentration-time curve from hour 0 to the last measurable concentration (AUC0-t), area under the concentration-time curve extrapolated to infinity (AUC0-inf), apparent terminal elimination rate constant apparent terminal elimination half-life (t1/2), apparent clearance, and apparent volume of distribution.

  • 2) Urine and Feces PK Parameters

Amount excreted in urine over the sampling interval, renal clearance (CLR), and the percent excreted in the urine, amount excreted in feces over the sampling interval, and the percent excreted in feces

  • 3) Metabolites

Metabolites of [14C]-DRUG MOLECULE and their PK parameters will be identified and calculated as deemed appropriate, based on plasma and urine concentration levels.

The secondary outcome measures involved in Phase 1 Clinical Trials include

    • Signs, symptoms, incidence, and severity of adverse events (AE)
  • Abnormalities in clinical laboratory assessments, vital signs, electrocardiograms (ECGs), and physical examinations.

How are ADME studies conducted in Phase 1 trials?

Mass Balance or ADME studies are carried out with male healthy volunteers by administering them with a single dose of the investigational drug labeled with Carbon-14. The cumulative radiolabeled dosage used in these experiments is approximately 50-100 μCi. It is based on the predictions of real tissue exposures from tissue distribution studies performed during preclinical trials involving animals. The volunteers are then kept in the clinical pharmacology unit (CPU) after administration until the radioactivity linked to the radiolabeled drug is quantitatively retrieved in the excreta (thresholds prescribed in the study protocol, normally in the range of 95% total and < 1Bq/ mL in the blood). Blood samples collected during the study are analyzed for the PK properties of the parent medication. The samples collected from this analysis are used in circulation and excrete metabolite profiling.

Conclusion

The human mass balance study is an essential study of the drug development process. ADME is also being carried out in the preclinical stage but the safety and efficacy of the investigational drug can only be validated after determining the absorption, distribution, metabolism, and excretion (ADME) properties of the investigational drug on healthy human volunteers. It can be rightly said that the human ADME (hADME) study provides a correlation between clinical observations and preclinical safety studies. The key objective of the hADME study is to quantify, characterize, and identify drug metabolites present in the systemic circulation.

References

  1. 1. Clinical Pharmacology 1: Phase 1 Studies and Early Drug Development, US FDA.
  2. 2. What is a Human Mass Balance Study? Accessed at

https://www.nuventra.com/resources/blog/what-is-human-mass-balance-study/

  1. 3. Why, When, and How to Conduct 14C Human Studies. Accessed at

https://www.sgs.pt/~/media/Global/Documents/Technical%20Documents/SGS-Clinical-14C-ADME-Clinical-Trials-EN-09.pdf

India – An attractive hub for clinical research

Advancement in medical sciences has benefited humanity in many ways. However, in the process of conducting clinical trials, incidences of scientific, moral, and ethical misconduct have been unearthed that have shaken up the scientific community and public. This led to the formation of a formal organization in 1979 by the United States (US) namely the “International Ethical Guidelines for Biomedical Research Involving Human Subjects” to protect and safeguard the interests of trial subjects. Following this, many countries drafted their own guidelines for Good Clinical Practices (GCP). However, with increasing number of clinical trials being conducted at sites in multiple countries, it was necessary to have a uniform guideline for conducting clinical trials. This gave rise to the International Conference on Harmonization (ICH)-GCP guidelines in 1996 with the objective of providing a uniform standard that facilitates the acceptance of clinical trial data by the regulatory authorities of the respective countries. Over the course of time, many countries adapted the ICH-GCP guidelines to frame their own guidelines. India too followed suit with the Indian Council of Medical Research (ICMR) introducing the “Ethical Guidelines for Biomedical Research on Human Subjects” that is continuously revised and amended to ensure that clinical trials are conducted with utmost quality, giving priority to the welfare of the subjects involved.1

India – A global destination

India is emerging to be a favorite destination for clinical trials for many international companies due to several factors:

☉  Conducive Regulatory Environment: Internationally harmonized and favorable regulatory processes such as fast track approval of investigational new drugs making the Indian clinical research environment more amenable to conducting clinical trial. Market trends show a compound annual growth rate (CAGR) of approximately 12% (US dollars 987 million) in the Indian clinical trials industry from US dollars 500 million in 2017.1,2,3,4,5

☉  Trained Manpower: Availability of skilled healthcare professionals who are specialists in different therapy areas, well-versed in the English language and who ensure compliance to ICH-GCP guidelines.1,2,3

☉  Technology Infrastructure: World-class technologies in data management and information technology and related services.1,2,3

☉  Patient Pool: Large population who are treatment naïve and have a diverse genetic and ethnic makeup. With India becoming increasingly urbanized and with greater connectivity between the urban and rural areas, it becomes convenient to recruit patients from different geographical areas. In addition, there is a high incidence and prevalence of acute and chronic diseases due to lifestyle changes leading to diseases such as diabetes, cancer, and so on. Such lifestyle-related disorders open up the possibility of conducting more clinical trials in these disease areas.1,2,3,6

☉  Ease of recruitment: In countries such as the US, approximately 86% of the clinical trials fail to recruit the required number of subjects leading to delay of almost a year. This delay costs the sponsor company several million dollars. Some of the reasons for delayed recruitment are unwillingness of patient to participate, stringent safety requirements, and hefty compensation packages. India provides the possibility of recruitment of patients with relative ease with due to increased trial compliance and transparency especially with the recent release of the New Drugs and Clinical Trial Rules 2019 that consists of updated rules and regulations for fast tracking approval of clinical trials. Among countries with fast growing economies, it has been noted that India has a growth rate in recruitment sites of approximately 22.6% with the highest growth rate seen in China (≈36%).1,2,7,8

☉  Competitive costs – Cost effectiveness is a pushing factor for many trials being shifted to India. The cost to develop a new drug is estimated to be almost 50% less than what would be required in the US or in the European Union. 1,2,3

Future of clinical research in India

Specific guidelines are being worked upon by the Central Drugs Standard Control Organization (CDSCO) for stem cell research, biosimilars, and medical devices to protect patients as well as to encourage clinical research and development in the country. After a lull period in the Indian clinical industry before 2015 due to ethical and quality concerns, open communication between sponsor representatives and the regulatory team of CDSCO has helped in reconsidering India once again as a potential global destination for enrolling a diverse population in clinical trials that adhere strictly to ICH-GCP guidelines.6

Sources

1. Das NK and Sil A. Evolution of Ethics in Clinical Research and Ethics Committee. Indian Journal of Dermatology. 2017 Jul-Aug;62(4):373-9

2.Burt T, Sharma P, Dhillon S et al. Clinical Research Environment in India: Challenges and Proposed Solutions. Journal of Clinical Research and Bioethics. 2014;5(6):1-8.

3.Bajpai V. Rise of Clinical Trials Industry in India: An Analysis. Hindawi Publishing Corporation. Review Article. ISRN Public Health. 2013:http://dx.doi.org/10.1155/2013/167059

4.Melissa Fassbender. India poised to become ‘one of the largest clinical trial hub’ says CRO. (2018). https://www.outsourcing-pharma.com/Article/2018/08/13/India-poised-to-become-one-of-the-largest-clinical-trial-hubs-says-CRO?utm_source=copyright&utm_medium=OnSite&utm_campaign=copyright Accessed on May 12, 2015.

5.https://www.medgadget.com/2019/01/india-cro-market-growing-at-an-impressive-cagr-of-12-by-2023-says-recent-study.html Accessed on May 12, 2015.

6.Reconsidering India as a Clinical Trial Location. Pharm-Olam. https://cdn2.hubspot.net/hubfs/4238150/PharmOlam_March2018/PDF/pharm-olam_india_clinical_trials_white_paper_1.pdf?t=1524594556831 Accessed on May 14, 2019.

7.Pathan IK, Nuthakki S, Chandu B et al. Present Scenario Of Clinical Trials In India. International Journal Of Research In Pharmacy And Chemistry. 2012;2(2):ISSN: 2231-2781

8.Luo J, Wu M, & Chen W. Geographical Distribution and Trends of Clinical Trial Recruitment Sites in Developing and Developed Countries. Journal of Health Informatics in Developing Countries. 2017;11(1). http://www.jhidc.org/index.php/jhidc/article/download/157/211

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For information, contact us at:

Veeda Clinical Research Private Limited

Vedant Complex, Beside YMCA Club, S. G. Highway,

Vejalpur, Ahmedabad – 380 051,

Gujarat India.

Phone: +91-79-3001-3000

Fax: +91-79-3001-3010

Email: info@veedacr.com