one of the very few interesting article by Microsoft Engineers on Clinical Research Industry. Certainly interesting as it is written by none other than      Les Jordan-CTO, Life Sciences Industry Unit at Microsoft . Microsoft and IBM had much longer and deepr association with Lifescience/Healthcare/Bioinformatics industry than Oracle.

But I love to see microsoft grow beyond Sharepoint for Clinical Research and the BioIT alliance. Also love to ask microsoft what is the current status of some of those applications mentioned in the blog by Les, Especially the Microsoft Clinical Trial Initiation solution

Original article from microsoft website

Interesting how weeks become months when you’re writing and updating blogs.  This CTMS project certainly hasn’t gone away, but it did go on a bit of a hiatus while my “day job” intervened.  Enough excuses.  Mea Culpa.  On to the fun!

As we discussed in the previous post, the key to a clinical trials management system is thinking of it in terms of a project – after all, the people who run the clinical trial think of it in terms of a project, and it is measured in project management terms, so why not treat it that way from an architectural point of view?

A second and equally important “requirement” is one that we are increasingly seeing as an industry trend: having EDC (Electronic Data Capture) functionality and CTMS (Clinical Trials Management System) functionality in the same system, or at the very least having EDC and CTMS closely integrate and interoperate.

The clinical trials world of today is fairly fractured.  Think of all the different systems – often standalone systems – that are used by Life Science organizations:

• EDC – Electronic Data Capture
• CTMS – Clinical Trials Management Systems
• CLIP – Clinical Investigator Portals
• Project – Clinical Trials Project Management
• Analysis – OK, it’s SAS, but how do you get the data there?  What about real-time analytics?
• IRB & DSMB – Outside organizations with their own management systems, like a Click Commerce Research Compliance Automation solution?

What if you could have a system that gets close to doing all of that – or at least being able to manage all of it – through one interface?  How much would that save in training costs, integration costs, and implementation costs?

Well – that’s the vision.  Here’s how we pull it off:

1. Start with Microsoft Office SharePoint Server 2007 and SQL Server 2008 as the foundation to build upon.
2. As discussed in the last post, we’ll use Microsoft Office Project Server as a way to organize the information and provide us with a trial specific taxonomy, along with roll-up of reporting metrics.
3. To cover the EDC aspects, we’ll utilize Microsoft Office Forms Server 2007 – which is a web facing InfoPath solution – to handle data entry and front-ending the workflow for data checks, etc.

EDC forms in Forms Server can even handle digital signatures (with compliance and security being the subject of a future post) inside the InfoPath forms.  This has implications for those organizations that are involved with SAFE BioPharma (worth checking out).

The beauty of all of this is that it is all Web Service enabled, which means that you have easier integration mechanisms with existing analysis and EDC systems:

• SAS – With integration with .NET, SOAP, and Web Services.
• Medidata – We’ve demonstrated use of their Web Services API module that utilizes CDISC.
• Perceptive Informatics – At the DIA annual meeting a couple years ago, we did a demonstration using DataLabs (now Perceptive) and InfoPath integration, using Web Services and about 5 lines of code!
• EHR/EMR Integration – While it is still on the horizon, I think it is getting closer.  Check it out.

Resources to get you started:

• Configuring SharePoint for 21 CFR Part 11 Compliance
• Project Server and Office SharePoint Server 2007 Integration
• Project Server Architecture and Programmability
• InfoPath Forms Server Form Template Authoring
• Microsoft Clinical Trial Initiation solution

Finally – there are other organizations and software vendors that are thinking along these lines.  Check out the following solutions:

• A solution in place in the US Department of Veteran Affairs
• TENALEA – Trans European Network for Clinical Trials Services
• Transenda – An Office & Project based CTMS system
• StreamLogic – A Project Based CTMS system

Next up in this series:

• Using MOSS templates for maintaining Part 11 compliance
• Extranets & Identity Management
• Architecture Diagrams & Screen shots
• Validation and compliance

I had posted last month about the Pegasystem pharmacovigilance solution.

Pega Systems the industry leader in Business Process Management (BPM) software solutions, released a Pharmacovigilance case processing software.

Pega has experience in clinical trial space, specifically in Clinical Trial Management. The solution is designed for rapid deployment to quickly leverage existing adverse event processing rules and requirements and can produce specialized documentation to help ensure compliance in a validated environment.

I have not come across any new updates after that. But apparently Accenture  has acquired Knowledge Rules, Inc., a Philadelphia-based consulting company that focuses exclusively on implementing and integrating business solutions using Pegasystems’ Business Process Management (BPM) software.

Accenture has a very large Pharmacovigilance division serving several large pharmaceutical companies. It would not be very suprising if Accenture roles out the BPM software for their pharmacovigilance services.

I think that is a possibility because Accenture  has announced plans to use the applications for all its Fortune 500 customers.

I would predict that United Health Group could be one of those customers as they are an existing customer of Pega.

Speaking of which Pega sounds like an attractive target Oracle can acquire

Laboratory Corporation of America Holdings…announced…a collaboration between Esoterix Clinical Trials Services, a division of LabCorp, and Clearstone Central Laboratories, a global central laboratory specializing in drug development and pharmaceutical services.…The collaboration provides LabCorp with access to Clearstone’s global network of labs, including China, France, Singapore and Canada, in addition to LabCorp’s existing labs in the United States and Belgium. The companies will collaborate on providing standardized central laboratory testing for clinical trials to their respective clients. The transaction also provides LabCorp access to Clearstone’s clinical trials management system APOLLO CLPM clinical trials management software, enhancing the ability of clients to conveniently send, receive and manage data.

APOLLO CLPM is a secured globally accessible web based, 21 CFR part 11 validated clinical trials management software. Designed and developed by subject matter experts of every applied discipline integral to the system. Built on an Oracle database, the APOLLO CLPM system is a truly singular database that replaces multiple legacy systems and sub-systems, helping to drive improvements in efficiency and quality across the central laboratory business Apollo provides for global standardization of requisitions, reports, kits, barcode labels, as well as scientific information, and improves the accuracy and speed of sample reception and processing

The multinational pharma companies are planning to approach the health ministry with a proposal calling for the utilisation of the 1.7 lakh post offices across the country to distribute over the counter drugs.

The move if implemented would increase the reach of OTC drugs by 20%.

The plan initially submiited 2 years ago requires  the approval of and coordination between department of pharma under the ministry of chemicals and fertiliser, department of post under ministry of communications and the health ministry.

The Organization of Pharmaceutical Producers of India (OPPI), an association of multinational pharma companies, is in the process of reviving the proposal as top officials at the health ministry have shown interest in discussing it and considering its implementation

The Indian over-the-counter (OTC) medicines market, the 11th largest globally, is pegged at $1.9 billion. It is the second fastest growing market globally with a growth rate of around 9% per annum.

Ranjit Shahani, country president, Novartis gives the analogy of the how petrol pumps have metamorphosed into multi-utility centres in last two decades. “One simple legislation can change that for over the counter medicines,”

Would you support this, even in US where people are more educated and FD keeps a watch on drug advertisement , people are often misguided.

India is yet to come up with a strong and comprehensive adverse drug event reporting infrastructre.

Scott Stern, Associate Professor, Kellogg School of Management, speaks on the topic of, “New Drug Development: From Laboratory to Blockbuster to Generic,” at the Judicial Symposium on The Pharmaceutical Industry: Economics, Regulation, and Legal Issues, hosted by the Northwestern Law Judicial Education Program

There have been several cases where Fraud in clinical trial has questioned the  Integrity of Data and ethics , when conducting clinical trial in India, which have been used by crusaders against outsourcing. But the new evidence suggest that the clinical trial fraud is more prevalent even in US. The most recent being MannKind Corporation Accused of Covering Up Adverse Clinical Trial Results

India’s poor history on adhering to patents, strong legal system, and the image of corruption means, any fraud in conducting clinical trial in India will invite serious punishment from FDA and western world. Yes we can cry that we will be singled out , or we can take necessary steps to avoid incidents such as above

MNC pharma MannKind is accused of Data Fraud Coverup  in securing FDA approval for Afrezza the inhaled insulin drug. A senior manager uncovered unlawful clinical trial conduct pertaining to the company’s Afrezza inhalant insulin device.  John Arditi, who was MannKind’s senior director of worldwide regulatory affairs, filed a wrongful termination lawsuit against his former employer, in New Jersey Superior Court, claiming he was unfairly fired by MannKind after internal audits he conducted in November 2009 uncovered “potential fraud and scientific misconduct” involving Afrezza clinical trial data

Arditi discovered discrepancies in data at both a Russian and Bulgarian trial site, according to his lawsuit.  For several months, Adverse event results were either not being recorded properly, or were fabricated to favor the approval of Afrezza.  Arditi’s lawsuit asserts that he informed superiors at MannKind, on November 9, 2009, of his adverse findings and encouraged the company to approach the U.S. Food and Drug Administration (FDA) but MannKind did not contact the agency because negative information would delay approval of the New Drug Application (NDA) for Afrezza.

The new revelation on MannKind Afrezza Clinical Trial that emerged last week , comes just days after the report published by The Council for Clinical Research Subject Safety & Data Integrity (CCRSSDI)  on widespread fraud in the Clinical Trial drugs by pharma and CROs in Unites States.

Two time Emmy winning reporter Kathy McDevitt led an investigative team from The Council for Clinical Research Subject Safety & Data Integrity (CCRSSDI), to record Subjects committing fraud. Her investigation led to on-air confessions by two such subjects on the nature and the extent of the fraud in the industry

Ms. McDevitt and CCRSSDI have jointly released a documentary tilted “Pervasive Fraud in the Clinical Trial World” . It is available on the CCRSSDI website. Copies of the DVD may also be requested by the video.

Among the findings in the documentary:

• Multiple simultaneous trial enrollments by Subjects
• Inability of research sites to check for dual clinical trial enrollments
• No single record of all the studies a subject has taken
• Inability to verify amount of actual drug usage by a Subject in a Study
• Potential for flawed results in Studies

Watch the Documentary on YouTube

“I was shocked by how lax the identification process is for potential Study Subjects”, said Kathy McDevitt. “I always had assumed that a thorough identification and verification was required to enroll qualified patients in studies for drugs that you and I take”

Kerri Weingard, the Director of CCRSSDI, further adds “We here at the Council have consistently raised this issue. Many members of this Council run their own Study Sites and we have seen the level of fraud increase year after year. Unfortunately, no steps are being taken by the industry as a whole to combat this problem. If this problem is left unchecked, the whole industry will suffer and public confidence in our Drug Testing process will be fundamentally undermined”

CCRSSDI has led the charge on this issue. Its charter clearly defines that the primary goal of CCRSSDI is to ensure that every study by every site and every sponsor utilizes and identification and verification process to ensure that there is no fraud occurring and that subjects are not dual-enrolled or have been expelled from previous studies.

Download the explosive documentary “Pervasive Fraud in the Clinical Trial World”, at http://www.CouncilForClinicalResearch.com

For further information please contact Kerri Weingard, Director, Council for Clinical Research Subject Safety & Data Integrity at KWeingard(at)CouncilForClinicalResearch(dot)com or 646-225-6624

Council for Clinical Research Subject Safety & Data Integrity is composed of established members of the medical profession. Its goal is to ensure that our testing process for Clinical Research Trials remains error free and that Subject Safety is always assured. meetings are open to all. For further information please email  at info@CouncilForClinicalResearch.com.
ONE of Australia’s most senior cancer specialists has accused pharmaceutical companies of manipulating some clinical trials of medicines for commercial reasons, including deliberately delaying the release of negative findings and being reluctant to fund research into the toxicity of their drugs.  More details

Professor Stephen Clarke, who has conducted clinical trials involving humans for 15 years, agreed to speak publicly for the first time because he said it was essential for governments to fund trials of great public importance rather than leaving critical research solely to drug companies.

A number of researchers who spoke to The Age agreed, saying commercial decisions meant the public did not always get the full picture about a drug’s usefulness and safety.

Other more high profile clinical trial related issues in recent past are PPD Inc responsibility in Ketek Trial for Aventis

The FDA found the fraud 2002 in a trial supervised by PPD, the doctor was indicted 2003, convicted 2004 and Ketek was approved 2004 by the FDA using the faulty data. It wasn’t until early 2006 that liver problems in patients using Ketek came to light and subsequently, the continued reliance on the fraudulent data. Congressional hearings were called for in 2006 which were held 2007 and again 2008 when Fred Eshelman, founder of PPD testified

The FDA and drug maker Aventis were directly faulted. Eshelman washed his hands. . This clip is one of three showing Fred Eshelman’s verbal responses to questions.

Some of the other high profile cases are

News that Schering-Plough, one of the largest drug companies in the world, has been outright bribing physicians to prescribe drugs and operate sham clinical trials http://www.naturalnews.com/001298.html

University of California findings in the October issue of the Annals of Internal Medicine, that 167 placebo-controlled trials published in peer-reviewed medical journals in 2008 and 2009 and found that 92 percent of those trials never even described the ingredients of their placebo pills.

The Utah Attorney General has filed a lawsuit charging GlaxoSmithKline illegally marketed its controversial Avandia diabetes pill as a new “wonder drug” that would reduce cardiovascular risks for diabetes, but instead increased the possibility of heart attacks. Consequently, the AG alleges Glaxo hoodwinked the state Medicaid program out of $7.8 million, which is the amount Utah spent to purchase Avandia between Jan. 1, 2001 and June 30, 2010

The more recent events in India were

Glenmark Pharmaceuticals and Omnicare have closed a clinical trial site in India operated by the contract research organisation (CRO) amid accusations that an investigator acted fraudulently.

Clinical Trial Fraud – How to Identify and Steps to Handle If Found, events like these makes adherence to GCP and training of CRA, and all stake holders in clinical trial more and more important

Had an interesting chat with the CEO of the US based IT service provider for clinical research industry in June. Apparently the company a SalesForce.com partner introduces new CTMS application in India. Just came to know that they are going commercial this month. The applications is aimed at clinical trial management, Study site management and Patient Recruitment in the clinical research industry . Aimed at CROs, Hospitals, University Research centers and clinical trial Study Sites.

The application is based on Force platform by SalesForce and already have few Indian Organization using it for several months. The product will be offered in SaaS/Hosted/Cloud versions, which will render affordable TCO and higher ROI with less or no Capital investmental.

Implementation of a computer-automated safety surveillance system of clinical outcomes registries for cardiovascular devices resulted in the identification of a drug-releasing stent that had significantly higher rates of major adverse cardiac events than similar stents

“Monitoring the safety of approved medical products is of vital public health importance, given that in clinical practice such medical products are often used in numbers far greater and in patient populations more diverse than when studied in premarket evaluations and clinical trials,” the authors write. “Ensuring the safety of medical devices challenges current surveillance approaches, which rely heavily on voluntary reporting of adverse events. Automated surveillance of clinical registries may provide early warnings in the postmarket evaluation of medical device safety.”

“In conclusion, automated safety surveillance of medical devices is feasible using automated monitoring tools applied to detailed clinical registries and can efficiently help identify emerging potential postmarket safety risks. Automated medical product surveillance can complement existing public health strategies, providing an additional mechanism to assess the comparative safety of approved medical products and improve the quality of health care delivered,” the authors write.

Original article on

http://www.scientificcomputing.com/news-DA-Computer-automated-System-for-Identifying-Medical-Devices-with-Safety-Risks-111110.aspx