Why Internet-Based Clinical Trials Are Prime For Biotech

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By Peter Feldman

In the biotech and pharmaceutical world, taking a drug therapy from conception to market is a long process that involves years of clinical trials and development.

Based on the enormous volumes of data that must be collected, stored and analyzed, and the required tracking and follow-ups, it is surprising that this area of research and development has been slow to transition to an Internet-based model.

In 2000, information technology experts forecasted that Internet-based clinical trials were on the verge of explosion. A market research study conducted that year by Medical DataBanks, a company that provides data solutions to manage clinical programs, identified that only 10 per cent of clinical trials were Internet-based. A follow-up market study in 2007 identified the same penetration rate of only 10 per cent.

Why hasn’t Internet-based technology been embraced in the area of drug research and development? It appears the prospect of widespread adoption of Internet-based clinical trials lies with the biotech companies.

The History
In the late 1990s, the future of Internet-based clinical trials looked promising.

Venture capitalists were pouring money into the Internet sector and many vendors entered the marketplace. But when the dot-com bubble burst, the capital quickly dried up, as did the software being developed.

There was also much scepticism of Internet-based clinical trials during this risk-averse period in the pharmaceutical industry. The reliability of software; the sustainability of the data management vendor; confidentiality and the security of data on the Internet—all were challenged. After the dot-com collapse, industry confidence in Internet-based applications declined further. Many pharmaceutical companies chose to stay with established CROs who continued to use a paper-based model.

Low-risk, incremental innovation was more readily adopted, which improved efficiency of various aspects of paper-based trials.

For example, optical character recognition services that could transpose faxed case report forms into a database reduced the need for human intervention and provided a partial alternative to remote data entry.

Another example was periodic trial enrolment status reporting, which was made more available to sponsors on the Internet. These temporary innovations were welcome, demonstrating there was a definite use for the web in clinical trials.

Another factor that impeded the adoption of Internet-based clinical trials was that from about 1999 to 2003 there were many mergers of major pharmaceutical companies.

As these companies were repositioning their key decision makers, it was difficult to find an innovation champion.

This put a halt to the introduction of mission-critical innovations, which included moving to Internet-based processes for clinical trials.

The initial set-up cost of web-based solutions was another barrier to their widespread use in clinical trials, as this set-up price tag was slightly more expensive than for a paper-based alternative. What many companies didn’t buy into was that Internet-based trials would be less expensive in the long run and could help get products to market faster. This is because data collection is more efficient, and the information being gathered is generally of higher quality, with a decrease in the number of records that have to be followed up, queried or written off.

Causes of Bottlenecks in Clinical Trials
Developing a clinical trial is a complex process that involves scientific, legal, regulatory and ethical frameworks. There are numerous steps in the development of a clinical trial, and delays can occur throughout the process.

Clinical protocol design – There are often several scientists and investigators involved. Design and approval can be impeded due to their limited time availability.

Ethics review board approvals – Approval times for protocols can vary from two weeks to three months, depending on study complexity.

Site recruitment – Securing a commitment from research sites, especially when they are in different countries around the world, can be time consuming.

Subject recruitment and retention – Participating study sites may have difficulty recruiting enough subjects or eligible subjects based on inclusion/exclusion criteria. There can also be issues with subject attrition due to early withdrawal or protocol deviation.

Subject follow-up – Ensuring investigators are following up with subjects at the appropriate intervals as outlined in the protocol, and that the required data is being accurately collected can be a challenge.

Site follow-up – When there are many site locations that are geographically dispersed, it can be difficult to coordinate the tracking and reporting for all sites.

Data entry into database – Investigators are not always kept up to date about when they are scheduled to see research subjects, the timing of follow-up visits, etc. Site management methods for case report form completion and submission may also vary. Sites may also fax or courier data to a coordinating centre for review and entry. Monitoring of sites typically brings data to a 95-98 per cent accuracy level, leaving statisticians to weed out the final queries for correction prior to locking the database.

Investigation sites – The administration and management of investigation sites can be complex with issues including continuity, site management tools, site reimbursement, competing interests, source documents, communication tracking and audit trails.

Benefits of Internet-based clinical trials
An Internet-based clinical trial can provide solutions for many of the causes of bottlenecks, and offer advantages over paper-based data collection. The Internet provides a real-time project management solution—once the subject enters the system, the database manages the timelines and actions that need to be completed at various stages as defined in the protocol. It is easier to monitor the entire process to review data in real-time and identify any potential problems with quality, schedules or protocol deviations.

A single trial or a strategic data management platform for a clinical development program can have substantial benefit to the overall costs and timelines. Internet-based clinical trial solutions are now more cost-effective than paper-based trials for any phase, whether using the database for remote data entry or centralized double-data entry of paper-based trials. Also, the integration of clinical, genomic, proteomic and general biological data in the more advanced clinical research databases is a novel capability that facilitates research for many new biological therapeutics.

The future of Internet-based clinical trials
By 2010 analysts predict biotherapeutics will be 25 per cent of all pharmaceutical sales and increasing by a 13 per cent compound annual growth rate (CAGR). By 2013, nearly 20 per cent of pharmaceutical industry sales are vulnerable to patent expiry. Success rates of first in human-to-market are less than 5 per cent for pharmaceuticals and 21 per cent for biotherapeutics. In 2009, new pharmaceutical product pipelines are not holding much promise of growth without further industry consolidation.

In the industry today there are indications that Internet-based clinical trials are on the rise. These solutions are being adopted more quickly by the biotech companies. Both the cost advantage and timeline reductions are now more compelling than ever.

The biotech market has a huge pipeline in the pre-clinical and clinical stages. In the early phases, although the studies are smaller and paper-based clinical trials are manageable, there are still many benefits to be realized by adopting a web-based solution.

Biotech companies see the value in contracting a specialty service provider to deliver an Internet-based process. By outsourcing the data management of clinical trials, they don’t have to invest in or develop their own database infrastructure. They can still conduct paper-based trials for these early phase studies if they choose, with the provider managing the data entry. Using an Internet-based solution also ensures more efficient data collection due to continuity and consistency which leads to higher quality data, and can help get the drug therapy to market faster. As studies move through the various clinical trial phases, Internet-based solutions will become increasingly essential.

Companies considering a web-based platform for a clinical development program will benefit from the simplicity of accessing and accumulating safety data. Regulators are often providing conditional approvals subject to detailed safety monitoring or registries being setup for the first N patients or the conditional period. The tools to support the conditional approval criteria are frequently implicit in the same clinical trial database. These tools provide the observational study platform and even the dose recommendation platform for a biological product, and can help in disease management, compliance and outcomes performance.

Once a drug is approved by a regulator, many governments, insurers and payers of drug benefits are now requiring economic justification of a product before they will accept it onto their formulary. These economic reviews have been evolving into primary data collection studies, often including medical histories, multiple standard measurement instruments and probability games. Some payers are even demanding proof of outcomes and cost effectiveness as a contractual condition of listing. Internet clinical trial databases have proven themselves in managing these studies as well.

It is now evident that all the negative issues from the early 2000s are past and a new market for Internet-based clinical trials has emerged. The clients are the biotech companies who are more aggressive and receptive to technological innovation.

These solutions will be delivered by established specialty service providers with a proven track record in the marketplace. Their web-based platforms deliver advanced security, confidentiality and high quality data that have realized time and costs savings for scores of clients. In the near future, it is likely that the industry will continue to see an increase in Internet-based clinical trials, with biotech companies leading the way.

Peter Feldman is a Founder of Medical DataBanks. For almost 10 years, Medical DataBanks has been providing research and administrative data management platforms for pharmaceutical and biotech companies, health providers and payers. Medical Databanks is based in Toronto, with corporate affiliations worldwide. Peter Feldman may be contacted by email at: peter.feldman@medicaldatabanks.com

Other benefits of Internet-based clinical trial solutions include:

Quality of data – Ensures information is more complete, provides consistency in data collection and entry, and enables more efficient follow through for longer studies.

Accuracy of data – Logic can be built into the solution with required fields, acceptable ranges, opening more detailed questions or pushing out additional forms based on the answers, all ensure the accuracy and completeness of data collected.

Flexibility – Information can be entered by an investigator or research coordinator at the investigation site, or if centrally entered by a double-data entry team, the same Internet database can be used, or a combination of both methods.

Easier regulatory submissions– When submitting study information to regulators, the data is available in electronic format so sending files and summary documents is faster and easier, with less administrative help required.

Project management and monitoring– Real-time databases provide real-time snapshots of trial progress and status. The workflow of document management amongst sites, monitors, data managers and project managers prevent items from being missed and provides alerts of activities and queries that are behind schedule.

Regulatory compliance requirements– The self-documenting procedures of Internet clinical trial databases for all data entry, monitoring and project management communication ensure that regulatory and legal criteria are a standard component of every transaction. This includes date and time stamps, electronic signatures, and the storage of every image of a data change, query or approval on a case report form. Each case report form is typically touched between five and ten times – for a typical phase 3 trial this can result in an audit trail of 100,000 -1,000,000 images. A self-documenting database ensures the trial integrity and can provide a real-time history of all activities.

Faster time to market– When a drug patent is granted in Canada, it has a 20 year life span. If it takes 12 years to get a drug to market, the company only has eight years to market the drug before it goes generic. In a phase 3 study, Internet-based data entry could reduce time to market by several months, and for a clinical development program, this time can be reduced by up to one year. This can translate into millions of dollars in additional revenue and longer protected access to the market.