Tuesday, 20 November 2012

Opportunity in the field of Drug Development – Smoking cessation

Antismoking foundations have sprouted at regular intervals consistently in different parts of the world, with an objective of overcoming the addiction to smoking. Various products have been undergone clinical research for efficacy and safety. There have been abundant developments in the form of extraction and novel delivery of nicotine that is devoid of dangerous and hazardous chemicals that usually part of smoke. Developments have evolved and promulgated into electric cigar and Trans dermal patches etc. Novel products with the variation in delivery system such as these are acting on the same receptors where the active from smoke too act. i.e., nicotinic receptors. Hence, there exists a scope for products that are devoid of nicotine. 

Lately, Varenicline an active is indicated for Smoking cessation. It is found to be more effective than NRTs and nicotine agonists1&2.  Among the recent developments, Champix found to be the best of the rest. Drug of this kind work through the mechanism of competitative inhibition and prevent the nicotinic effects.  Nowadays, Clinical trials are being focused on towards the development of antismoking vaccine3

Recent news suggests that around 4.1 milliion US dollors have gone in drain through an exhaustive clinical trial performed by Glaxo – Nabi collaboration for vaccine. The objective of that vaccine was supposed to induce the creation of an antibody; this in turn intends to prevent the transportation of nicotine through Blood Brain Barrier.  These concepts and drug targets are food for thought for those in the drug discovery and development fields. Currently, there are around 1.1 billion smokers in the world and these numbers are increasing steadily day after day; therefore, developments in the field of smoking cessation is the field that could be tapped by the pharmaceutical companies.

1.   a b Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, Billing CB, Gong J, Reeves KR (2006). "Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial"JAMA 296 (1): 56–63. doi:10.1001/jama.296.1.56.PMID 16820547.
2.   a b Mills EJ, Wu P, Spurden D, Ebbert JO, Wilson K (2009). "Efficacy of pharmacotherapies for short-term smoking abstinance: a systematic review and meta-analysis"Harm Reduct J 6: 25. doi:10.1186/1477-7517-6-25PMC 2760513PMID 19761618.

Wednesday, 7 November 2012

Is There a Hope For Type II Diabetes Patients ?? 

There are lots of clinical trials that are happening in the field of diabetes treatment. Most of the trials are focused on the adjuvant therapy and also on improving the existing delivery mechanism. Recently in the news about a phase II trial conducted for a product Imeglimin, a novel compound as an add-on therapy to Sitagliptin (Imeglimin-Sitagliptin Therapy Shows Significant Benefits In Type 2 Diabetes." Medical News Today. MediLexicon, Intl., 5 Nov. 2012. Web 6 Nov. 2012. For more info, visit Medical News Today).
As per the bulletin, the combination found to be effective in reducing the blood glucose. News of this kind is common nowadays and most of the results are from the early stage clinical trials. The sample size of this particular trial is just 150 and it is certainly not a size on which the decision can be made. The majority of trials fail in the 3rd phase of the clinical trial and mostly due to the increased number of variables and sample size. Hence, news of this kind is certainly not the answer for the long wait; however this can provide a glimmer of hope for the type II diabetic’s patients.

Thursday, 11 October 2012

India A High Risk Country for Misconduct in Clinical Research

I) Introduction

Clinical Research is a scientific discipline wherein numerous data is getting generated in different location on a daily basis. There are various players who are responsible for the generation of these data. Moreover, these data do influence the decision of the sponsor and the regulatory authority in commercializing the tested product. It is significant to note that the data that is getting generated can be genuine or fraudulent and therefore will have an impact on the wellbeing of the society. The way and the manner in which the clinical trials are being conducted will have to be taken into serious consideration by each and every professional in the Clinical Research industry.
The point of discussion of this article is that, whether India is a high risk country for misconduct in Clinical Research or not.

When we mention misconduct, it is an “intentional wrongdoing” and in the case of fraud it is a “willful deception”. Does India carry out intentional wrongdoing in the field of Clinical Research, a question to be answered by the professionals working in CRO and Pharmaceutical Industry in India? It is true that India is an important destination for clinical trials but we can’t deny the fact that it is one of the most vulnerable countries for the fraud and misconduct. The reason why India is a leading destination for conducting Clinical Research is enumerated below:

II) Resource advantage

1) Investigators
  • Large No. of specialists and super specialists in the field of science and research
  • English trained medical professionals
  • PG trained physicians from Europe/US
  • Large no. of ICH/GCP trained individuals.
2) Patient population
  • Large, Diverse, therapy.
  • Advantage of having 6 out of 7 genetic varieties.
  • Large amount of patient pool in acute/chronic disease segment.
  • Increase in no. of cases like AIDS and cancer.
3) Clinical Research Infrastructure
  • Over 200 Medical Colleges.
  • Over 22,000 graduates per year.
  • 15,622 hosp., 903,952 hosp.beds >75% in urban area.
  • 14000 diagnostic labs.
  • 700,000 scientists and engineering graduates / year.
  • World class medical / lab facilities.
4) IT Support
  • Highly developed IT / ITES
  • Motivated & committed personnel
5) Connectivity
  • High quality digital connectivity.
  • Excellent transport facilities across country

III) Number of Clinical trials from India:-

(www.clinicaltrials.gov; 15 Apr08)

Clinical Trials
No. Of clinical trials from India

IV) Who is responsible for the fraud?
  • This includes
  • Sponsor or CRO.
  • CRAs.
  • Investigators and
  • IRBs or ethics committees.
It’s not just the matter that who has been involved in the fraud but it’s the matter of negligence which can affect the lives of many innocent consumers.

In the clinical trial most of the activity is often delegated by the Principal investigator to the CRC or nurses .Many trials involve a regular dose of medication in which the patient will come to the investigator for administration of this product. A doctor will often examine the patient for serious side effects and leave it up to a nurse to administer the medication, although many of these nurses are very competent. However, nobody is perfect which can sometimes lead to the fraudulent activity.

Many companies offer recruitment incentives to doctors involved in studies, as they get more patients into the studies, the doctor receives more money. The main problems associated with recruitment incentives will cause a physician conflict of interest as a result of which doctor might recruit the subject that may not fit for the specific trial

Conflict of interest has been defined as “a discrepancy between the personal interests and the professional responsibilities of a person in a position of trust” (Orlowski and Wateska, 1992).

V) Why India A High Risk Country for Misconduct

1) Sites
  • Low awareness of regulations, ethics and GCP amongst investigators, CRC,CRA and ethics committees.
  • Lack of proper system to document the data.
  • Scarcity of trained research staff.
2) Sponsor
  • Dual quality in clinical trials – local vs. MNC
  • Unnecessary focus on speed rather than focusing in quality and integrity of trial.
3) Regulators
  • Lack of system of inspections and review procedures.
  • Lack of awareness.
  • Lack of proper Guidelines.
VI) Why Fraud in India:-

There is a school of thought, which says that the reason for misconduct in India is due to lack of regulation, lack of transparency and accountability.
In 2006, WEMOS and the Centre for Research on Multinational Corporations prepared an overview and found that out of 22 unethical cases around the world, 8 cases are from India.

The Indian examples of illegal and unethical trials
  • Sun Pharmaceuticals and Novartis’s Letrozole for inducing ovulation when approved only for breast cancer.
  • Novo Nordisks for diabetes treatment.
  • Solvay Pharmaceuticals for treating diarrhea.
  • Johnson and Johnsons for treating acute malaria.
  • Pfizer’s for cardiac events.
  • Otsukas for arterial disease.
  • Indian companies Shantha Biotechnics and Biocon for diabetes and
  • John Hopkins University’s trials for treating oral cancer.
In recent years, India has made some regulatory attempts
  • Amending its drugs and cosmetics act
  • Good clinical practices (GCP) guidelines
  • The ethics committee that the ICMR has formulated.
  • But there is still no compulsory compensatory payment, or penalty against the defaulting company. Ethics awareness in India is developing and the law superseding, but still there is deficiency in working out solutions for improving the act of fraud and misconduct.
VII) Dealing with Misconduct
  • Identify and eliminate risk factors for misconduct
  • Increasing the period of monitoring and auditing can help detecting the fraud.
  • Promptly investigate and report fraud and try to correct them as soon as possible to reduce the deviation from the truth.

VIII) Conclusion

Even if a new product doesn't work or we don't know how it works, there is pressure on managers to get it reviewed and approved.

The Clinical trial process takes up a lot of time and money on the part of the sponsor. Often the company has high hopes for a specific product that in reality the product just may not meet. No company wants to invest all of the required money for the trials if they are not going to make a profit from it. As a result there may be more fraudulent activity, even when the product has been reviewed and approved. In order to improve these fraud and misconduct, it is essential that has the broader objective that is overall well being of the society.

Sunday, 16 September 2012

Importance of Clinical Data Management


Clinical data is one of the most valuable assets for a pharmaceutical company and these provide vital confirmation of a drug’s efficacy and safety. Massive amount of data is collected during the entire life cycle of clinical research. Data management serve as the basis for

  • Collection
  • Storage
  • Validation
  • Analysis
  • Submission
  • Approval
  • Labelling
  • Marketing of a compound

Clinical Trial data can come from a variety of sources:
  • Investigator sites.
  • Laboratories.
  • Directly from subjects and partners.

Clinical data management (CDM) system plays a vital role in clinical trials to ensure high-quality data are captured effectively and ethically by sites staff through paper case report form (CRF) or electronic case report form (eCRF). Data collected through various phases right from the phase zero trials. These captured data are designed and made accessible for early review. Collected data will be utilized to characterize the subject/patient population and also to evaluate the safety and efficacy of drug. Structured databases are used to collect, organize and analyze clinical data. Sponsor is responsible for the integrity and quality of data and this could be ensured by collecting and transferring data from study subjects to a clinical data management system.

The sponsor of the drug will rely on this data to secure the marketing rights. However, even in the case of a clinical trial producing negative results, clinical data provides certain informational advantages to its holder for e.g.,Clinical trial results can be applied to make adjustments to other R&D projects in the same or a related therapy area and also assist in forecasting the probability of the R&D programme leading to a marketable product. A key condition for the subsistence of database rights is that there must have been ‘a qualitative or quantitative substantial investment in either the obtaining, verification or presentation of the contents of the database.

(CDMS) must be monitored, to ensure a reliable and effective base for
  • New Drug application (NDA) Submission
  • Clinical Science Reports
  • Clinical Planning
  • Decision-Making
  • Process enhancement
According to the Data Warehousing Institute (DWI) estimates the cost of bad or ‘dirty' data exceeds $600 billion annually.

Cost per patient of Clinical Studies
The cost per patient of clinical studies of new pharmaceuticals 

No of patients involved
Phase 1
exceeds $26,000 per patients
Phase 2
$19,300 per patient
Phase 3
$15,700 per patient.

$46,784,000 per average trial

If all the data collected during the clinical trial are invalid or unacceptable. How much would be the cost? Therefore, it is vital that CDM follows a systemic process and an established mechanism to avoid colossal loss in terms of finance and valuable resources. In order to prevent these irreparable mistakes, data collection and verification process will undergo validation at every stage. This will ensure that the data is clean, useful and consistent

Reason For erroneous data

Errors inevitably occur during data entry. Most common errors include:
  • Typographical Errors
  • Copying Errors
  • Coding Errors

Prevention of erroneous data 
Prevention of erroneous data can be carried out through various set of established mechanism as below:
Edit checks and queries.
For example, it will not allow input of future date as "visit date", or enter any other gender then male or female etc.  

Data Entry tools
The effective use of data-capture tools ensures that high-quality data are available for early review and rapid decision-making 

Data clarification form should be maintained for clarification of queries that arises during discrepancy management

Trial monitoring is to verify

  1. The rights and well-being of human subjects are protected
  2. The reported trial data are accurate, complete and verifiable from source documents
  3. The conduct of the trial is in compliance with the currently approved protocol/amendment(s), with GCP, and with applicable regulatory requirements.
Sponsor should ensure that trials are properly monitored. Part of monitor responsibilities, depending on sponsor request, is to verify data consistency with the source data or documents:
  1. Dose or therapy modifications
  2. Adverse events
  3. Concomitant medications and/or intermittent illnesses
  4. Visits, labs, examinations and tests required by protocol, but failed to perform.
All the above mentioned process can be done in an effective manner if we have Data management plan (DMP) in place.

Benefits of DMP:-
The work to be done and responsibilities are clearly stated at the start of the study so everyone knows what is expected.

The expected documents are listed at the start of the study so they can actually be produced during the course of rather than after, the conduct of the study.

Benefits of Data Validation
Missing data identification.
Handling missing data for data cleaning purposes must answer following questions:

  • Was missing data collected on CRFs?
  • Was missing data lost during data load or database manipulations?
  • Was missing data loaded fully and correctly?

If all those questions are answered "Yes" then data cleaning job for missing data is completed.
Data reconciliation, which take place at the end of clinical trial and refers to a process that compares two sets of files to make sure they are in agreement
Queries that arise during the reconciliation of the data should be handled in the same manner in which clinical queries are handled Standard operating procedures (SOP) and quality analysis should be a part of every study

Conclusion:-But it is still a challenge for most of data managers and clinical team leads to distinguish "dirty data" from actual Protocol deviations. In fact, it is essential to have full, clean and accurate data to determine the Quality, safety and efficacy of the product.



Tuesday, 11 September 2012

Clinical Research Companies & Organizations – Careers in India


Clinical Research is the fastest growing sector of Health Care Industry and it is some of the most creative, forward-thinking in the business world. Clinical research is a part of Life science deals with the case study of safety and effectiveness of medications, instruments, diagnosis and products.

Clinical Research gives a wide range of cultural, educational and geographic backgrounds which helps your ability to work in a dynamic professional environment that values individual perspectives. There is a chance of huge career openings in this area, according to the British clinical research organization there is a need of 20lac clinical research professionals for the year 2015 globally.

To acquire the Best Research and Placement oriented Clinical Research program in Bangalore Avigna Clinical research institute is the leader which gives the great learning experience. In addition, ACRI placement cell will assist you the career opportunities. We have a wide and strong collaborations with the Leading MNC's and some are listed below.

Here we listed some of the Top MNC’s Clinical research Industries and their profiles::

 Semler Research Center              careers@semlerresearch.com

 Indegene Lifesystems Pvt Ltd       info@indegene.com


           Quintiles                           www.quintiles.com/careers/


           Avigna Group                     careers@avignapharma.com


Glorigin Lifesciences Pvt Ltd           info@glorigin.co.in

 Cadila Pharmaceuticals                  careers@cadilapharma.co.in

    Advinus Therapeutics Ltd.            info@advinus.com

     APC Global                             APC Pharmaceuticals & Chemicals

ARIANNE Clinical Research            info@ariannecorp.com
Organization ______________________________________________________________________________
        Aris Global                              careers@arisglobal.com         

Columbia Asia Hospital                       kalappa.kb@columbiaasia.com

KPS Clinical Services Pvt. Ltd            career@kpsclin.com

 Lambda Therapeutic Research Ltd.    careers@lambda-cro.com

           Max Neeman                      hr@neemanasia.com

     © Avigna Clinical Research Institute , Bangalore