Biotech Strategy Blog

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

Posts tagged ‘informed consent’

Richard Schilsky in Science Translational Medicine describes the challenges of enrolling patients into ever more complex cancer clinical trials. It is estimated that only 3-5% of cancer patients participate in clinical trials. Can social media be used to overcome barriers to enrollment?

There are many barriers to enrollment such as a lack of incentive by the physician if they can prescribe the drug off-label and obtain reimbursement, the additional legal liability, time required for research documentation and the need to follow human protection requirements such as informed consent and obtain Institutional Review Board (IRB) approval.

There’s also the issue of equipoise, the uncertainty as to whether a new treatment will be beneficial or not and the need to discuss with a patient their willingness to accept the risk that a new treatment may offer less benefit than the current standard of care. This topic is beyond the scope of this post.

Schilsky notes in his commentary that:

“trial start-up times have lengthened to an average of 2 years or longer, up to 40% of cooperative group phase III trials have failed to complete accrual and closed without achieving study endpoints, wasting the contribution of those patients willing to enroll in the trial.”

Time to market is key to the success of biotechnology and pharmaceutical industry, with product life governed by patent years. Delays in time to market have a real ROI impact, and may lead to promising products being discontinued prematurely.

One of the barriers to enrollment noted in Schilsky’s highlights is “insufficient patient awareness/demand.” Can social media play a role in overcoming this?

To look at what is happening currently, I used Storify, a new tool that allows you to create stories using social media:


ResearchBlogging.orgSchilsky, R. (2011). Accrual to Cancer Clinical Trials in the Era of Molecular Medicine Science Translational Medicine, 3 (75), 75-75 DOI: 10.1126/scitranslmed.3001712

BBC health reported this past week on the news that Professor Dr. Joachim Boldt, the former head of anaesthesia at the Klinikum Ludwigishafen hospital in Germany had published 102 papers in leading academic journals without first having obtained ethics committee (EC) or institutitional review board (IRB)  approval for the research.

These studies on patients undergoing surgery or intensive care led to the development of new guidelines for managing the administration of colloids for fluid replacement during surgery. Questions are now being asked about the validity of these scientific findings and whether any fabrication of research data took place.

When Dr Boldt submitted research for publication he indicated that EC/IRB approval had been obtained, a claim that was not checked by any of the journals.  It now appears that EC/IRB approval had not been obtained. Last week the editors of 16 leading publications formally retracted the papers they had published from Dr Boldt.

The news that an anaethetist failed to obtain informed consent or EC/IRB approval for clinical research comes as no surprise to me.

I conducted anaesthesia breathing system research in the early 1990’s in a joint industry/academic partnership program. My research was published in the British Journal of Anaesthesia, who also published several studies from Dr Boldt.

At that time, many of the anaethestists I worked with questioned the need for patient informed consent for research with a new breathing system. They argued the patient would have to use one anyway during the operation, and even if this was a research study it was not necessary. Requiring formal signed informed consent for the clinical trials I did was a novel experience for some of the anaethetists I worked with.

Indeed, if the editors of the journals were to look closely at european clinical research related to medical devices published prior to EC Directives and standards such as EN540, ISO14155 coming into effect, they might find that many researchers did not obtain IRB/EC approval or informed consent for that work.

I think the journal editors are right to condemn the lack of research integrity that took place with Dr Boldt.  All of us in the pharmaceutical, biotechnology and medical device industries who undertake clinical trials to bring new products to market rely on the goodwill of patients to participate in the medical research process.

The news that Dr Boldt did not respect the rights of individuals, and failed to follow the Declaration of Helsinki, the fundamental “Ethical Principles for Medical Research Involving Human Subjects”, published by the World Medical Association, undermines the integrity of the clinical research process for all of us.

Moving forwards, I would suggest that the editors of journals require authors to submit a copy of the EC/IRB approval letter/notification with their manuscripts.  Any form that just requires you to tick a box or sign off to show compliance is open to potential abuse by a very small minority.

All EC/IRB approvals have to be in writing, so this step would not be an onerous burden and would provide some confidence of valid ethics approval, and in the process support the integrity of the clinical trials that we all rely upon.

If you would like to follow this issue in more detail, Ivan Oransky, on his excellent Retraction Watch Blog has been writing about this story since last October.

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.

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