There was a zeal among the clinical research community with DCGI’s announcement of “Registration of CROs in the country will become mandatory from June in view of glaring deficiencies found during the audits as the sponsors, monitors and Contract Research Organisations (CROs) do not adhere to protocols”. This decision embarked a new rising of the Indian regulations.

However, few days later there were reports of  “A new drug to combat diabetes, which is administered orally and not injected, was given a marketing approval by the Drugs Controller General of India (DCGI) without being put through the mandatory human clinical trials”.

As per the Drugs and Cosmetics Rules any change in route of administration makes even an old, approved medicine, a ‘new drug’ making the clinical trials mandatory.

Anoop Misra, director and head of department of diabetes and metabolic diseases, Fortis Hospitals who reviewed the published papers said, “Most of this data are preliminary and anecdotal, and do not make a strong case for it. Its safety remains to be demonstrated, especially in view of (the) fiasco of inhaled insulin.” He has not prescribed the drug to any patient as the side effects are not clear due to inadequate data.

Once again the practitioners would be in the lime light in view of their ethics and GCP while prescribing such a drug.

As the softwares are becoming the backbone of clinical trials, the costs of softwares supporting the functioning of clinical trials is also rising. In such a scenario the future of open source softwares look promising. Cost-effectiveness, regulatory compliance, feature-sets, easy installation and easy training are few of the features which makes open source an alternative for clinical research. Let us discuss these is detail…

Cost-Effectiveness

Since, cost is a major factor for most of the start ups and mid-sized CRO/pharmaceuticals, the option of open source softwares is becoming reasonable. With EDC and trial management systems like OpenClinica, TrialDB, OpenCDMS, PhOSCo, FIREBIRD, ASTER, etc. erupting, setting up of data management function is becoming easier. Due to infrastructure investment issues many of the small scale CROs tend to outsource data management activities to third parties. However, with open source softwares coming into picture investments have become negligible. Thus, allowing capturing, cleaning, extracting, and storing trial data achievable by the individual CRO. This addresses most of the challenges faced by the developing countries due to limited basic information systems infrastructure. What we need is computer, Internet connection and people who can operate them, that’s it!!!!

Regulatory Compliance

With improving technology taking up the show, the challenges to ensure that the data collected, stored and analyzed electronically are in compliance to the regulations have increased. Hence, most of the open source systems are designed in compliance to globally used guidelines like Title 21CFR Part 11, HIPPA, etc. This ensures that the data captured, stored and analyzed are in compliance to the global regulations.

Feature-Sets

Most of the open source softwares are designed to support all types of clinical studies in diverse research settings making them flexible for variety of trials. Some systems like OpenClinica, PhOSCo, TrialDB and OpenCDMS provide solution right from Management of numerous/diverse clinical studies – Data submission/validation/annotation – Data filtering and extraction – Study oversight, auditing, and reporting. While some software like FIREBIRD and ASTER provide solutions for specific domains i.e. FIREBIRD provides investigator registry while ASTER provides solutions for Adverse Event Reporting.

Easy Set up and Training

Open source softwares allow easy set up of the system as the software is freely downloadable. The instructions for set-up and installation are easily available on-line. This makes set up on the whole, an easy process. The free demos for the systems are available on-line, allowing anyone and everyone to understand operations easily and undergo self training without anyone’s help. This makes the training part easy as well.

“All these above characteristics provide alternatives for clinical research industry but how willing is our industry to try this out. The willingness of the companies will come when more and more vendors approach with their software options to the companies, when the consultancy firms will come up with these ideas which would lower the budget significantly. More awareness and willingness is the need of the time.”

Related Links:

Is Biopharma ready for open source software?

Could an Open-Source Clinical Trial Data-Management System Be What We Have All Been Looking For?

Ethical Issues in India:

There are several reasons for occurrence of ethical issues in India. Some are due to ignorance and some due to conflict of interest. A few of them are listed below-

• Literacy status: This majorly impacts the process of Informed Consent. The patients are not able to read and hence cannot understand their rights to information and access to health care. Patients normally consider the doctors as God and completely trust them for the treatments which is unfortunately misused by some of the practitioners for their benefits.
• Economic status: This again impacts the voluntary decision of the patients. Due to low economic status the chances of exploting patients becomes high. Sometimes even the investigators are given lucrative offers by some of the sponsors to enroll patients.
• Standard of care: The best standard of care is not uniform and hence has high potential for exploitation.
• Conflicts of interest in terms of role and finances.
• Conflicts between Practice and Research commonly know as Practice vs Research.
• Deficiencies in IRB”s: Lack of trainings & monitoring, unawareness about informed consent procedures being followed, etc.. are the few deficiencies seen in IRB’s (as per WHO, National Bioethics Commission, Regulatory Agencies of Non-US sites)

Possible Actions/Solutions to encounter Ethical issues:

Lately there has being a lot of noise over the current scenario of laws to penalize and monitor pharma companies which have messed up or violated norms while conducting global clinical trials for testing drugs in India. The regulatory authorities were alarmed after the death of an infant during a clinical trial on whom multinantional Wyeth’s advanced pneumonia vaccine was being tested in Bangalore. In light of which the DCGI had suspended the vaccine trial. At this point of time it was realized that we still lack in some laws to punish the guilty who have behaved unethically in conducting the clinical trials. Hence, a immediate action was taken by the health ministry by finalizing the Central Drug Authority (CDA) bill which will frame laws as well as tighten existing regulation on clinical trial and introduce a central licensing mechanism for manufacturing approvals.

Recently another issue was raised when it was found that many US companies are testing drugs in countries where they do not intend to sell them which has created serious ethical concerns. Why cant we pool in more trials which would provide equal chance for creating market for such products like trials for Tuberculosis or malaria or dengue. How credible would be the data for such trials if required patient pool is not available here?  And very easily we point out the finger towards regulatory agencies. As professionals why don’t we take up this task to ensure that we follow ethics and so do the people working around us. After all we are the key people who are in the field and monitoring the progress of the trials. If we as individuals seek for ethics automatically we can drive others to do the same. After all charity starts from home….

(Thanks Louis for your guidance)

These were some actions required/taken to deal with the unethical practices. If you have some solutions or scenarios, kindly drop in a comment. It would be interesting to see some inputs and comments from you….

Posted in Ethics in Clinical Research, Uncategorized ]]> http://shruts25.wordpress.com/2009/03/11/possible-solutions-for-ethical-issues-in-india/feed/ 6 shruts25 http://shruts25.wordpress.com/2009/02/16/developing-basic-it-infrastructure-for-clinical-trials/ http://shruts25.wordpress.com/2009/02/16/developing-basic-it-infrastructure-for-clinical-trials/#comments Mon, 16 Feb 2009 17:40:01 +0000 Shruti http://shruts25.wordpress.com/?p=48 ]]> For any R&D company to run smoothly requires appropriate back up system to be in place. Especially while conducting clinical trials (which has become multicentric with simultaneous trials being running across the continents) the need of proper infrastructure is required. Large amount of data is generated and handling this large data becomes an integral part of the research. Hence, an entire separate branch of data management is dedicated for this. But today here I am going to discuss of what goes into making this infrastructure. What I am discussing here is very general but still plays important role.

As I was going through the process of “Product Life-Cycle  Management (PLM)“, I figured out that the product life cycle goes through many phases which involves many professional disciplines, and requires many skills, tools and processes. Although PLM is the term commonly referred by the marketing professionals, if we get the concept right it can be applied wherever we talk about bringing the product from labs to market. Now, in this case if we talk bout a product which would be an efficient software handling all the data generated “Product Life-Cycle  Management” could be replaced by “Software Development Life Cycle (SDLC)“. Now what is SDLC???

SDLC is the process of creating or altering systems, and the models and methodologies that people use to develop these systems. The concept generally refers to computer or information systems. In other words we can say that SDLC involves all the steps from planning—-to execution—–to maintenance of the product.

Now, the question is how does SDLC come into picture for clinical solutions?

The answer is it does plays an important role. As discussed earlier the data generated while conducting trials need proper archival, analysis and statistical conclusions. If we start doing this manually it is going to take ages for a product to come to market. Hence we need softwares to do this work for us… For this we need people from all the sectors to come together. This area therefore, requires individuals with expertise in different sectors. Here you will see people from all sectors coming together to give the final outcome. Hence, we can call Clinical Research as a multi dimensional industry requiring expertise from all different sectors. Let us see how this is achieved.

Going back to SDLC….SDLC adheres to important phases that are essential for developers, such as-

1. Initiation / Planning,
2. Analysis,
3. Design, and
4. Implementation

Let us see how this 4 phases will get us to the outcome…i.e. in this case an IT infrastructure to support clinical trial…

1. Initiation / Planning: This gives a high-level view of the intended project and determines the goals of the project. It begins when the sponsor identifies the need or opportunity. The concept or proposal is generated. Feasibility studies are done in typically 3 areas – economical (requires commercial expertise), operational (requires subject specific expertise in this case clinical / life sciences expertise) and  technical (requires IT expertise). Thus you can figure out that since the initiation of the project we need individuals coming from 3 sectors and working under a same roof. By end of this phase we have a ‘Project Management plan in place’.
   
2. Analysis: This phase mainly deals with the analysis of the users requirements. The entire project is broken down into different segments making it much easier to visualize and divide the responsibilities.  By end of this phase we have a detailed ‘Functional Requirements Document in place’.
3. Design: This phase deals with system designing, coding and testing. This phase is mostly dedicated to IT professionals, however, life sciences individuals are consulted as required.
4. Implementation: Once the software has undergone a hard core testing, the software is implemented for practical use. However, initially this is monitored constantly as practical scenarios have their own queries. These queries are resolved and thus over a time the software then works at the efficiency  of 99%. Thereafter, it is maintained.

This gives a basic outline for developing the basic infrastructure for the clinical trials. There can be slight changes in the development process as per the requirements.

At this point I would like to discuss about a key contributor in the above mentioned life cycle. In normal IT environment that key contributor is called “Business Analyst“, however, in Clinical Research we don’t have a proper term designated to this role some call them “Clinical Trial Project Assistant” or a “Product Specialist”. As the terms suggest they play an important role right from the initiation to the implementation of the project. They are a key link between the Clinical team and the IT team. Hence, they need a broad spectrum knowledge of both clinical trial as well as IT work processes. They need to know the needs of both the teams and should have a capability to communicate the queries / requirements in a right manner. Hence, making it a challenging role. We dont get to hear about this role quite often in our industry but yes it is meant for people who like to take up challenges and has the ability to accomplish the same…Hope to see more of such roles in near future.

Here is one of the links which gives detailed information.

http://www.ibpassociation.org/pdf/IBPACareersBrochure.pdf

Clinical Research is concerned broadly with inquires into all aspects of health and disease in man, using human beings as the units to study.

Next question would be why is it required? The answer is before we bring the medicine / drug into the market we should be aware that the drug is safe to be used into patients. We do studies in animals to check for the safety of the drug but after all their systems are different than ours and hence we need to test the drugs on humans as well before we bring them into market. Also we need to know the Risk : Benefit ratio because if the drug is effective (beneficial) for a particular disease but gives 100s of side effects (risk) whats the use of such drugs. Hence we quantify the Risk : Benefit ratio during our research.

Clinical Research strictly follows certain guidelines and constant monitoring of applicable regulatory agencies to safe guard the basic rights of the subjects / volunteers participating in clinical trial and to ensure the credibility of the data. Some of the guidelines include -

• International Conference of Harmonisation (ICH) – GCP (Good Clinical Practice) – Globally accepted guidelines
• Schedule Y (Law in India)
• Indian Council of Medical Research (ICMR), etc.

Definition as per ICH-GCP:

Clinical Trial / Study is “Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of an investigational product(s), and/or to identify any adverse reactions to an investigational product(s), and/or to study absorption, distribution, metabolism, and excretion of an investigational product(s) with the object of ascertaining its safety and/or efficacy. The terms clinical trial and clinical study are synonymous.”

Types of Clinical Trials:

1. Treatment trials test experimental treatments, new combinations of drugs, or new approaches to surgery or radiation therapy.
2. Prevention trials look for better ways to prevent disease in people who have never had the disease or to prevent a disease from returning. These approaches may include medicines, vaccines, vitamins, minerals, or lifestyle changes.
3. Diagnostic trials are conducted to find better tests or procedures for diagnosing a particular disease or condition.
4. Screening trials test the best way to detect certain diseases or health conditions.
5. Quality of Life trials (or Supportive Care trials) explore ways to improve comfort and the quality of life for individuals with a chronic illness.