Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts from the ‘Imaging’ category

Following on from my blog post last week that discussed the use of iPads and other tablet computers in clinical trials, MIM Software have just received FDA 510(k) clearance to market their iPhone and iPad medical imaging app in the United States. This is the first such approval by the FDA, and the app will be sold in Apple’s itunes store.

This new mobile radiology application will allow physicians to review medical images on their iPhone and iPad.  The FDA in their press release indicate that it is not intended to replace full work stations, but to provide the ability to view images and make diagnoses when a workstation is not readily available.

The FDA reviewed luminance, image resolution quality, and results from demonstration studies with radiologists that showed that images could be safely interpreted for diagnostic purposes under appropriate lighting conditions.

What is more, using software from MIM, the images can be further analyzed and distance measurements made.

The ability to have wireless access to medical images will be particularly useful to physicians working remotely, in emergency situations and in clinical trial networks where the central imaging review facility may not be local.

As the screen resolution of iPad’s and other tablet computers increases, perhaps we will see advanced visualization software available on the iPad?  It is certainly an area where innovation is taking place, and one that I think will impact clinical research in the biotechnology industry before too long.

I was supposed to be at the Innovation in Healthcare Symposium today at MIT in Cambridge, MA, but the winter ice storm that’s set to hit the North East has forced me to change my plans and return early from Boston to New Jersey. I am hoping to outrun the storm this morning (unlikely I know).

Hopefully, the presentations will be videoed and uploaded to You Tube or Webcast. Having traveled to Boston specially, I’m disappointed not to be able to write about the Symposium as planned.

A hot topic that came to my attention courtesy of an article in the Irish Medical Times, is how companies are handling incidental findings in the medical images they obtain during clinical trials.  To me, this is the flipside of innovation in that it often yields both positive and negative consequences.

Innovative medical imaging such as positron emission tomography (PET), Optical Coherance Tomography (OCT) and Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) are now widely used in clinical trials, and have opened the door to new ways to visualize joints, blood vessels, organs and tumors.  This innovation is leading to the development of imaging biomarkers such as reduction in joint space or reduction in tumor size that became surrogates for drug efficacy.

However, in the process, these clinical trial medical images are generating “incidental findings” (IF).  An incidental finding is something that shows up in a medical image obtained during a clinical trial, but is not related to the clinical trial protocol or study objectives.  The challenges is that what the reviewing radiologist sees may impact the health of the subject, making it an ethical issue not only for the reviewer, but for investigators and sponsors such as biotechnology companies.  How companies handle incidental findings in clinical trial imaging is a hot topic at the moment.

Part of the debate is to whether this is something that companies should worry about, given that we are talking about may be a relatively low incidence.  A September 2010 paper from Fletcher et al, “Incidental Findings in Imaging Research,” published in the Archives of Internal Medicine, reported that 39.8% (n=567) of 1426 research medical images showed an incidental finding. Of these, in only 6.2% was clinical action taken upon the IF and in only 1.1% (n=6) was there resulting clinical benefit to the patient.  This raises the questions of to what extent there is an obligation to report findings, who pays for this, and whether it is ethically necessary?

The National Institute of Biomedical Imaging and Bioengineering (NBIB) has published recommendations, that states researchers should anticipate incidental findings and have a policy to deal with them.

If I were a biotechnology company looking to hire a Contract Research Organization (CRO) or other outsourcing company for central review of clinical trial images, one of the questions that I would ask is what is their policy for handling incidental findings?

While innovation in medical imaging provides new ways of measuring and detecting disease, this innovation also generates unanticipated data that has to be addressed.

The theme for the biotech strategy blog this week is innovation in bringing new drugs and devices to market.  Innovation is the lifeblood of the biotechnology industry and what drives the acquisition of companies for their pipeline by large pharma companies.

Tomorrow I will be at the Innovation in Healthcare Symposium at MIT in Cambridge, MA. See my earlier blog post for further information. I look forward to writing about the Symposium later this week.

One experienced industry professional recently told me that he believed the Ipad would revolutionize the clinical trials process.  Do you agree? On reflection, I think the IPad and similar tablets will make the clinical trials process more efficient, but is this an innovative breakthrough that will revolutionize the model? I am not so sure.

At this year’s Consumer Electronics Show in Las Vegas, analysts talked about the 80-100 new tablet computers that were on show, and the fact that an estimated 50 million e-books and tablets will be sold in 2011.  Companies have clearly innovated in bringing new technology to market, that we now have a desire for and want to use.

Health Professionals have embraced the IPad, it’s ease of use, portability and potential for a range of uses from data entry, to the viewing of medical images and access to online reference databases.  In the hospital environment, it can easily be integrated into the IT infrastructure and made HIPAA compliant if no data is stored on it.

For clinical trials, it is already being as an electronic data capture (EDC) interface for case report form (CRF) data entry, although I am not sure whether it will become the primary interface. My expectation is that IPads and similar tablets will increasingly be used as a portal for accessing study resources, the ordering of supplies, recording of adverse events and even the signing of patient informed consents.

I also expect we will see IPads being given to patients for clinical trial diary and journal entries. What’s more by using these devices with 3G wireless capability, study coordinators will be able to interact in real-time with patients, remind them of study visits and monitor medication compliance. Mobile health is set to be a real growth area.

On the medical imaging side, results from a clinical trial published at the Radiological Society of North America (RSNA) annual meeting last December showed that radiologists viewed the IPad imaging quality as equal or superior to standard LCD displays when viewing X-rays. (Erik Ridley wrote up a good post about this on AuntMinnie.com).

Reviewing X-rays to screen for TB is a lot different from diagnostic imaging in clinical trials, so I remain unconvinced that the IPad will take over for primary diagnosis, and central review of images is still going to be the gold standard.

What I think the IPad and other tablet computers will do is allow the easy sharing of images between the central review laboratory, investigators and study coordinators. This will make it easier to monitor patient inclusion, study progress and report imaging results.

So looking at the above, while I think the IPad is an innovation, I don’t necessarily think it will revolutionize clinical trials and bring products to market faster.  It will be interesting to see what industry professionals have to say at the Drug Information Association (DIA) annual meeting later this year.

What are your thoughts on how innovation will change the clinical trials process in the biotechnology industry? How can we bring products to market faster?

Last week on January 20, 2011, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee decided not to recommend approval of Lilly’s Amyvid™ (florbetapir) in a 13:3 vote.  Florbetapir is an imaging agent used with Positron Emission Tomography (PET) to show accumulation of beta-amyloid plaque in the brain. I previously wrote about Lilly’s acquisition of Avid Radiopharmaceuticals for florbetapir on this blog.

This imaging approach aids in the early detection of Alzheimer’s disease, as a negative scan, not showing any beta-amyloid plaque, would rule out Alzheimer’s disease.  Given that it is currently, hard to distinguish age related memory less and different types of dementia, diagnostic imaging tools have an important role to play.

The FDA advisory committee’s decision would probably have come as a surprise to Lilly, since the clinical trial data showed clear efficacy and no safety concerns.  While the committee rejected immediate approval, they did recommend approval (16:0), conditional on a training program to show that radiologists and readers of the scans could be accurate and consistent in their image interpretation. The FDA is not bound by the Committee’s recommendations but is required to take them into consideration when deciding whether to grant approval.

Imaging is becoming increasingly important in clinical trial design. In therapeutic areas such as osteoporosis, rheumatoid arthritis and oncology, imaging end points are often surrogates for drug efficacy.

The challenge that emerging biotechnology companies face in linking imaging to drug use, is the variability of readers outside a controlled clinical trial environment where images may be read centrally.  Standardization of image acquisition and reading needs to take place, so that a radiologist in different hospitals can come up with the same findings.  Those involved with imaging clinical trials know how hard this can be, even within the controlled clinical trial setting.

The recommendation of the FDA advisory committee that Lilly needs to put in place a training program to show accuracy and consistency of readers is a valid concern and one that all biotechnology companies and pharmaceutical companies should take note of when developing imaging agents.

A company I have been watching for a while is Philadelphia based Avid Radiopharmaceuticals, now a wholly owned subsidiary of Lilly. They have a novel imaging biomarker, florebetapir (18F-AV-45) in development for the detection of Alzheimer’s disease.

In a press release last week, Lilly announced that the FDA had assigned a priority review to the marketing application of florebetapir. The Peripheral and Central Nervous System Drugs Advisory Committee of the FDA meet on January 20, 2011.

Bayer have a competitor product in development, forebetapen (BAY 94-9172). Both florebetapir and florebetapen are 18F radiolabelled imaging biomarkers that bind to amyloid plaque in the brain.  When used in conjunction with a Positron Emission Tomography (PET) scan, they enable the accumulation of amyloid that occurs in Alzhemeir’s disease to be visualized.

Phase 3 trial results for florebetapir published earlier this year showed that the brain amyloid burden seen in the PET scans positively correlated with the plaques seen in autoposies of the same patients.  Proof that what the imaging biomarker shows is an accurate representation of the underlying pathology.

What makes the use of florebetapen and florebetapir interesting is that it is already common practice to use imaging tracers with PET scans. Fluorodeoxyyglucose (FDG) is widely used in the diagnosis, staging and treatment of oncology patients as a result of its ability to show the intense glucose uptake that occurs with most cancers.

Both Avid and Bayer products are most likely to be approved based on the clinical data presented to date.  It will be interesting to see the prices that they intend to charge.

As for the market opportunity, they are likely to have a role to play in the early diagnosis of patients with mild cognitive impairment, since at present it is difficult to diagnose these patients and differentiate Alzheimer’s disease from other forms of dementia.  Most likely, models will be developed that look for a correlation between accumulation of amyloid plaque and decline in cognitive function, from which a probability of developing Alzheimer’s disease can be calculated.

Imaging biomarkers are likely to place an increasingly important role in the development of new products by biotechnology companies and in the design of clinical trial endpoints.

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