Bio-Imaging

Source: Exec Digital

Date :23/05/2007 11:39:55

Bio-Imaging: Windows to the Soul

Written and produced by James Buchanan & Patrick Harlow

The search for cures requires looking into the human body, which is Bio-Imaging’s specialty

Cancer is no longer the automatic death sentence it once was.

Key to being able to make that claim is the plethora of new drugs and treatments that have come into use over the past ten to twenty years. Lives have not only been prolonged, but saved, as the disease becomes more manageable than it once was.

This does not mean the fight is over, not nearly. But it does point to growing research success. Supporting this research is an industry providing support services, and among those, medical imaging management by companies such as Bio-Imaging Technologies, Inc., is one of the most productive.

Once the domain of lead clad x-ray technicians, medical imaging now encompasses a number of modalities from Computer Tomography (CT) scans to Magnetic Resonance Imaging (MRI), ultrasound, Position Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT). With so many diseases undergoing studies, so many modalities for images to be gathered, and so many formats being used, competing in this niche requires a broad breadth of capabilities.

“We are a one-stop shop for pharmaceutical companies because we can handle all imaging formats, many disease ranges, and imaging modalities,” says Dave Pitler, senior vice president of operations at Bio-Imaging. “So one pharmaceutical company with a number of trials for a broad range of diseases can come to us and we are able to handle all of their trials. They only need to coordinate and hire one company.”

Bio-Imaging is one of the world’s largest, independent dedicated providers of medical image management for clinical trials. The company has worked for more than 100 pharmaceutical, biotechnology and medical device companies around the world, including many large, multi-center studies.

The company receives, manages and reads images for pharmaceutical trials. According to Pitler, clinical trials are conducted all over the world. Study subjects (patients) in the various trial sites have an image taken, which is immediately assessed by the subject’s doctor as a therapeutic assessment of the patient’s condition. For example, in a cancer study, the patient’s doctor would check to see if the cancer is showing signs that it is shrinking or in trials for rheumatoid arthritis treatments the doctor would examine for bone erosion.

Once the images are acquired at the clinical of hospital they are sent to Bio-Imaging. Bio-Imaging takes the images and anonymizes them to essentially hide the patient’s personal data.

All of the images from all of the related study sites are then standardized so the reader sees a series of images without personal information or differentiating characteristics. The intent is that no matter where the trial is being conducted – the US, Russia, China, Europe – the images are indistinguishable from each other in terms of presentation, to provide the most accurate assessment by the reader to measure the effect of the drug.

Standardization (which includes “blinding” and bringing the images to one common platform) is critically important to the validity of the test results. Therefore, Bio-Image employs the first of its three trademarked technologies called Computer Assisted Masked (blinded) Reading Service (CAMR), which is a digital image display and call-up system for randomized reading. CAMR utilizes a logic-driven questioning system and is a completely controlled reading method.

CAMR consists of two linked computers: one to display images (with multiple monitors) and one on which the technologist enters radiologist’s input directly into the electronic case report form. Depending on the therapeutic area of the study, the CAMR presents the baseline and displays subsequent images in either random order or temporal sequence.

Working with the company’s second trademarked technology called BioTrack, CAMR creates a complete audit trail of the reading process, helps eliminate human error, and increases accuracy.

BioTrack is a tool used by the company to help ease company compliance with US and foreign regulations governing how drug trials are conducted. BioTrack is a custom-built project tracking database that enables a high level of image tracking and control for every stage of the image data process. This includes the initial site survey, arrival of images at the company’s labs, quality control checks, quantification, reading, and final submission of results to the US Food and Drug Administration. This system is also regularly audited by outside experts.

According to the company’s website, BioTrack “incorporates automatic logic checks and quality control measures, greatly reducing the chance of human error. A complete, automatically generated audit trail ensures CFR 21 Part 11 compliance, and maintains strict controls necessary for extracting optimum results from your data.”

The third in the company’s triumvirate of technologies is Bio/ImageBase, which is specialized data submission software. Bio/ImageBase is a customizable desktop computer software application created specifically to work within the parameters of a medical imaging study and in compliance with all FDA submission requirements. The software provides a combination of data selection and ad-hoc query features, medical image display and processing functions and, interactive image optimization tools necessary for clinical researchers, regulatory affairs managers and FDA medical reviewers.

Critical to the accurate assessment of drug trial images is consistent and skilled readers of those images. To conduct an independent reading, the company has assembled a number of leading therapeutic specific radiologists with expertise in specific modalities, anatomical sub-specialties, and disease specification. Each radiologist also possesses an in-depth understanding of imaging in relationship to clinical trials.

Using the company’s CAMR technology, each image is reviewed by the radiologist (reader) and a technologist as an extra step to ensure consistency and accuracy.

According to Dr. Colin Miller, senior vice president of medical affairs, given the totality of the services and skills the company offers along with the broad scope of the diseases the company handles makes it unique. “Other companies will handle only one or two disease areas,” says Miller.

Further, most other companies are not able to interface with as wide a variety of file formats as Bio-Imaging. “We can handle 95 percent of the world’s imaging data regardless of the format used at the trial site,” says Miller.

The company’s depth of formats also extends to proprietary imaging systems such as those used by Siemens, GE, Toshiba, or Phillips, Pitler says. In this way, Bio-Imaging can be thought of as something of a clearinghouse for trial images due to its combined abilities and broad range of diseases, modalities and formats.

Further, the company currently receives images from 10,000 cities in 63 countries, says Pitler.

Worldwide Scope…

The company is based in Newtown, Pa., with satellite offices in Leiden, Netherlands, and Lyon, France.

Having offices in Europe, says Pitler, allows the company to draw on a wider range of expertise while overcoming some of the more parochial feelings of Europeans. European companies have a preference to medical imaging companies based in Europe. Part of this attitude could be ascribed to the differences in regulatory regimes between the US and Europe. Having offices in Europe provides the company with another layer of regulatory expertise to match its US proficiency.

According to Miller, the Leidon office is a snapshot of the Newtown office as it has the same operational capacities, but without the software development capability.

Meanwhile, the Lyon office specializes in software development.

All data at all of the offices are coordinated via BioTrack, the company’s centralized database.

When asked about its acquisitions policy Pitler says the company “looks globally and we are constantly evaluating a number of companies around the world that through acquisition we could use to increase our capabilities and expertise.”

Before acquiring a company, both Miller and Pitler say, Bio-Imaging will usually have worked with it for a period of time as a subcontractor. Over time, Bio-Imaging learns about the company and becomes comfortable with it prior to taking steps to purchase it. Pitler says the Lyon office is a good example of this process. As its own company, it held strong software development skills and as the company sought to increase its international presence, especially in Europe, acquiring the company in Lyon made good strategic sense.

Playing by the Rules…

“We have a very good relationship with the FDA, very good in-roads with them,” says Miller, “which is necessary to help support our clients.”

Both Miller and Pitler say that being able to meet federal regulations is a very significant barrier to entry into their market. By merely being able to meet the stringent criteria of the FDA, Bio-Imaging crosses a significant hurdle and garners a very important competitive edge.

Looking forward, Pitler and Miller say regulations are becoming stricter in the area of patient privacy. Over the past few years Congress has passed laws making the protection of patient personal information a priority among medical care providers.

The same is no less true for the medical research industry where Bio-Imaging must make sure that all images are cleaned of personal identifiers. AIDS related trials are a good case in point, says Miller, “There is a high degree of concern that personal data is secure as it travels across the Internet from point-to-point or while being kept with us.”

Bio-Imaging internally and electronically masks all personal data after the image is received. The company must keep that data, but it is essentially hidden within the company’s network. An auditor, says Pitler, must not be able to track the image back to a patient at a trial site, but the company must be able to tie the image back to the trial site from which it came.

Europe is even more sensitive on this issue, adds Pitler. The company must certify that all personal data is hidden. The company also must be able to track the data back to its source, but not learn the personal information of the patient.

Since it is very common for an image to have personal data on it, and most images arrive via package delivery as opposed to electronically, an employee of Bio-Imaging looks at every image as it enters the building. Personal data is immediately dealt with before the image moves forward in the process.

Keeping not only personal data, but trial data as well from prying eyes requires Bio-Imaging to adhere to a strict security system and policies.

The company uses a three-tiered security clearance system to maintain strict control of its lab environment. The general security level has policies in place to maintain control over the reading rooms and areas for public visitors. The second level of security is for the company’s main rooms. To enter these areas requires security clearance, and are accessible only to employees and specially cleared guests accompanied by employees.

The highest level of security includes the regulatory filing rooms and rooms housing its networking hardware. Only regulatory filing personnel and network staff are able to access these areas.

The design is intended to enable the smooth flow of the image management process while protecting images from unauthorized viewers.

Also, all regulatory filing rooms and network rooms are protected with FM 200 Fire Suppression an environmentally safe, clean, waterless fire suppression system that can eliminate a fire within seconds.

The company’s network is built specifically for the needs of clinical trial image data, It includes a 25-terabyte RAID 5 storage system with snapshot backups, a dedicated server for BioTrack, and a fireproof safe for short-term storage. The company also has a specialized disaster recovery plan in place to provide an added layer of protection.

Asked about if the company is seeking to increase the volume of images received electronically, both Pitler and Miller said yes, but it is not as a simple as a standard file transfer protocol with data compression.

As the image formats and modalities become more complex and require large amounts of data, the resulting images are very large and difficult to send. Compression as of today is not really an alternative because of the risk of image corruption as it is compressed for sending and then decompressed after being received. Even the slightest change could prove very problematic for the trial outcome.

Pitler and Miller say that pharmaceutical companies and regulators take a fairly conservative view on this issue. For the FDA they want to ensure trial results are valid, as do pharmaceutical companies. Added to that, drug development is a very expensive proposition and the companies making these investments – hundreds of millions of dollars – do not want to risk losing that investment from a corrupted file, no matter how slight the corruption.

Looking Forward…

Pitler says there are three issues driving the companies growth – the number of trials, FDA regulations becoming more stringent, and the need to look internationally for patients to volunteer for the trials.

FDA regulations are getting tougher and more focused, which increases the barrier to entry for other companies and makes the trials more complex.

The FDA is also moving forward on its Critical Path Initiative, which consists of six focus areas related to clinical trials, Pitler says. Of those, one is the use of medical imaging to accelerate approval. For pharmaceutical companies and Bio-Imaging, increased use of images earlier in the process can bring go/no-go decisions on whether to proceed with the trial sooner saving a lot of money for trials that won’t bear fruit.

Finding patients is also an issue.

“The most difficult thing in these trials is finding patients that are drug naïve,” says Pitler, “meaning they haven’t already been using a number of drug therapies to treat their condition, which can throw off the findings of a trial. Increasingly, trials are going to Asia and Latin America to find patients.”

Internationalizing drug trials raises issues of language and documentation. Asked if the company is seeking to find sites within Asia or Latin America, Pitler says, “If this were to reach some form of critical mass we would consider setting up in these countries. For now, there is no need to expand into these areas.”