Clinical Trial Innovation – (1) Informed Consent

Over the next few months, we will be posting a series of articles that challenge typical methods applied in Clinical Trial execution today.  We expect arguments put forward to be challenged.  We don’t expect a conclusion to all, but we do believe that it is time that some of the standard practices and methods were challenged.  It is time to see significant changes.

Informed Consent is broken.

There is an inherent bias in how some patients are recruited into clinical trials.  [Simplified] Patients are referred to specialists, some specialists are involved in clinical trial research. Some specialists are under contract to provide a certain quota of patients.  If an investigator with financial pressures was presented with a potential volunteer that would make up their quota, would they be more inclined to persuade rather than inform a patient of the risks / benefits of a trial?   Certainly not in all cases, but, an opportunity for bias does exist.

Patients generally trust their doctors.  I myself will rarely argue with my Doctor.  If my doctor suggests a specific therapy, I will generally follow their advice.  That might also stretch to taking pre-approval research therapies.

So… assuming this does indeed occur, what are the implications.

A recent joint study by J&J and Bayer – a blood thinning agent, Xarelto – was rejected for approval for the treatment of  acute coronary syndrome.

“Were there not questions about loss to follow-up and missing data, it would have been a yes,” said Allan Coukell, a pharmacist and the panel’s consumer representative, when explaining his ‘no’ vote on Xarelto. 

So – why did this particular study suffer such a large % of loss-to-followup patients?   Looking more closely at the details of the study, it would appear that patients dropped out after suffering adverse reactions that should have been fully explained and accepted during the consenting process.

If the consent process was more effective in this particular study, would J&J and Bayer have seen such a high drop-out rate?  I would argue ‘no’.   Recruitment may have been more challenging, but on balance, the cost of additional recruitment must certainly be lower than the cost of a rejected application.

Pfizer Direct-to-Patient Recruitment study problems.

On the other side of the informed consent world, we have the methods that were applied in the well publicised Direct to Patient (or as I prefer, Patient Centered) Detrol study. 

This study was recently cancelled with poor recruitment cited as a principle cause.

One of the aspects of the Pfizer study was that the patients did not go through the informed consent process face to face with the investigator physician.  The methods used to describe the implications of the clinical trial where therefore generic – the same for each patient – and potential verbose as a result.   Without the personal doctor/patient trust factor it is understandable that patients were unwilling to participate.

Middle Ground?

So… do we see a middle ground?   Technology companies are already aware of the limitations in the model that limits the patient/doctor interaction.  MyTrus announced in March 2012 the availability of an iPAD app that leverages multi-media to more thoroughly explain the implications of a study, and therefore achieve a more knowledge patient towards achieving informed consent.   A couple of other companies that attended the annual DIA also demonstrated electronic iPAD based Informed Consent solutions.

Do I believe that an iPad app is the solution to this challenge?   It will help. But obviously logistically it will only work with patients that have, or are given an iPad. Key though is that it will not solve the issue of the lack of a doctor/patient relationship.  However, I do believe it is a step in the right direction.  We will un-doubtable see technology innovation in this area over the coming months.

Regulatory changes?

Questioning the personal integrity of a doctor/patient relationship is a difficult one.  The Sunshine act in the States (now coming into force on Jan 1st 2012) whereby information on all forms of sponsor –> physician payment being made public might address some concerns around paid bias but doesn’t really tackle this particular issue .  Sponsor organizations do not wish to see a (further) reduction in patient recruitment numbers due to excessive regulations. However, at the same time, sponsors would like to see better patient retention ratios through the achievement of a better informed volunteer.  The need for additional clarity on the application of social media in clinical research from regulators is pending. Today – it is too early for such a position to be made – any statement made today will be out of date by the time it is released. However, as the ground settles with social media consistently becoming part of day to day lives, regulations must emerge that help sponsors apply this new medium appropriately.

In the meantime, it is up to innovators to set the bar on what can and cannot be leveraged effectively.  Done correctly – this can lead to a better informed patient, and a better quality of trial recruit.

Further information.

Beyond information above, we have some ideas that we are sharing with sponsor organisations in how the informed consent process can be adjusted to properly balance the need for patient awareness and versus patient engagement.  Feel free to contact us for further information.

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