A closer look at informed consent in clinical trials

The patient journey refers to a patient’s experience over the duration of care. Historically, the focus has been on the clinical steps of treatment but there are many aspects of the patient journey beyond just medical considerations, including financial, work, mental health and impact on the caregiver and family.

Equally, a patient’s journey can involve a lot more than just medical diagnosis and standard interventions.   An early decision point on the patient journey, particularly when receiving a serious diagnosis, is whether to participate in a clinical trial.  The bridge between patients and a clinical trial is the Informed Consent Form (ICF).  The ICF provides potential clinical trial participants with the information they need to decide on whether to volunteer for a research study.

 As the name suggests, there are two parts of the ICF, Informed and Consent.

According to Webster’s Dictionary. 

• Informed is having or showing knowledge of a particular situation; a decision or judgment based on an understanding of the facts of the situation

• Consent is giving permission for something to happen or an agreement to do something

Simply put, the ICF is meant to ‘inform’ the participant about the clinical trial and the patient provides his or her ‘consent’ to participate in the trial as described by signing the ICF.

Essentials Elements of the Informed Consent Form

There are three major elements of an ICF – disclosure of information (inform), competency of the participant or surrogate to make a decision (consent) and the voluntary nature of the decision (consent).  But let’s take a closer view through the patient lens.

It is critical for patients to understand the proposed clinical trial.  The ICF typically provides the potential participant with a description of the clinical investigation.  It outlines potential risks and benefits of the treatment and highlights alternative treatments that may be available beyond the proposed trial.  It covers the schedule for treatments and additional testing or scan requirements.  Usually, the primary investigator or other medical staff review the contents of the ICF and ask the patient if they have any questions.  But is this review enough?

I have reviewed many ICFs in my role serving on internal patient councils with pharmaceutical companies.  The documents are often overly technical scientifically and written with a heavy legal tone.  It is difficult for most patients and caregivers to understand.  After all, few patients have received medical training and do not understand the nuance of what they are reviewing. 

It’s like visiting a foreign country, where not only do you not understand the language, but you don’t even recognize the letters.  

While the medical staff does a very effective job explaining the contents of the Informed Consent Form, the person receiving the information may not be able to understand it in the form and language in which it is delivered.  The layout is confusing.  The flow is often disjointed.  It is not specifically written with a patient as its prime audience.  The goal must be for patients to ‘understand what they are signing up for.’

A few suggestions for study sponsors that should make the ICF easier to digest for patients:

1. Make it more readable for the patient.  ICFs are very dense documents – a lot of technical terminology, detailed tables and appendices, too many acronyms, inclusion and exclusion criteria that might be confusing and difficult to follow.  Informed Consent Form authors need to keep their audience in mind.  Use terms that are better understood by potential patients.  I appreciate that there may be a regulatory distinction between a side effect, adverse event or serious adverse event, but to patients, it’s just a side effect that must be addressed.  Help the patient understand what they are reading.  The MRCT Center at Brigham and Women’s Hospital and Harvard has developed a patient friendly Clinical Research Glossary that provides plain language definitions and examples of commonly used terms.  Additionally, more schematics and symbols should be used and fewer words.  As an oncology patient, I always think in terms of cycles – how long is a cycle, how many site visits are required, what is the sequence of events during that cycle -e.g. – treatment, bloodwork, scans, doctor appointment/telemedicine, providing patient reported outcomes via questionnaires.  It’s a better way to communicate - I’m more likely to remember the picture then a detailed appendix;
   

2. Highlight the benefits and risks so patients can understand these.  Patients do not want clinical trial sponsors to ‘over-promise or over-sell’ the potential benefits of participating in a trial. Patients are always wearing a WIIFM hat (What’s In It For Me). Too often in the spirit of being overly cautious, the potential benefits are under-emphasized, or they are positioned in an altruistic frame – by the patient participating in the trial, we will learn a lot more about the disease for the benefit of future patients.  Don’t misinterpret, altruism is a key driver for many clinical trial participants, but hopefully there could be some benefit to the participant.  Why not present the potential benefits and risks in a more balanced, understandable way?  After all, there is true patient benefit associated with being more closely monitored as part of the study – this should not be minimized.  ICFs are very thorough, including all the possible risks.  Another improvement that could help patients is to provide more details on the potential side effects.  Often these potential risks are presented without any communication of the likelihood of occurrence. Potential participants may be overwhelmed by all the possible risks and cause them to wonder why they would ever consider participating in a trial.  This is required to better inform patients;
   

3. Clearly articulate the patient burden (and associated burden for a caregiver) and take steps where possible to minimize this burden.  Participation in a trial often involves more frequent monitoring leading to more site visits for lab work, doctor appointments, or scans.  Can any of these be done more conveniently for the patient, be it at a local office or testing facility?  Or perhaps some appointments could be via telemedicine?  But let’s make it easy.  Provide the patient with a debit card to capture any covered expenses.  If possible, provide logistical support to help patients and caregivers make reservations and travel plans, be it ride sharing, flights or accommodations.  However, remember that every patient is different and his/her needs and preferences are different.  Ideally, trials should be designed to be flexible and allow patients to select the option that best meets their needs.
   

4. What costs are the patient responsible for?  This needs to be very clear, both for participation in the actual trial activities and beyond those activities should there be any additional cost implications.  For example, after the trial is finished, are there longer-term testing requirements for the patient?  Or might patients be faced with changes over the long term in their ability to secure insurance?  Patients must be informed.

Reaching an Informed Decision

Patients like me need more and should expect more.  They want to understand the trial – what is expected of trial participants?  Potential participants want to be confident that steps are being taken to minimize their burden; they want clarity of the potential risks and benefits.  This information is essential for the participant and caregiver to make an INFORMED DECISION - that is being a truly informed patient.  Potential participants should consider the tradeoffs, both those specific to the trial and those beyond the trial.  Equally important is the understanding of alternative treatments. Are better treatment options available?  Is there another trial that might be a better fit?  All these inputs will influence making an informed decision and be weighed by the personal circumstances and priorities of the patient. These priorities might be psycho-social, logistical, financial or other.  Patients have different circumstances, priorities and preferences which will influence their decision, but to make a truly Informed Decision, the patient must incorporate all considerations, trial specific and beyond.

Regarding consent, a participant’s competency to decide as an informed volunteer is key.  Consider the dynamics of the situation.  A patient has just received a potentially life changing diagnosis.  The patient is trying to quickly learn about the disease and digest information in a ‘foreign’ language.  In many circumstances, time is of the essence, adding additional pressure for requiring and making an informed decision.   The patient tries to determine if there are any trials available that meet his/her needs. The patient can be overwhelmed with information - like drinking from a firehose.

Searching online can be challenging for people without a scientific or medical background.  New tools, like Medifind.com or CenterWatch iConnect help patients find specialist doctors and clinical trials, but it is still a challenge. 

Is the patient ‘competent’ to make an informed decision at such a stressful time? 

 Many patients rely on their doctors to help them navigate to the best course of action, but non-research-oriented general physicians might not be aware of the relevant, most current clinical trials.  Many doctors are most familiar with clinical trials at their institution.  Physicians should be educated on how advocacy groups can support their efforts. Helping patients and families to become broadly informed, beyond just the details of one study, is so important.  The patient needs to trust the depth and breadth of the trial information and be confident they are making the best personal decision.  Patients should seek input and advice from beyond their general practitioners and the clinical investigators and engage disease specialists for their opinions.  Yes, the patient is competent to make a decision but perhaps not always confident that they are making the right decision.  

Finally, the voluntary aspect of consent is well covered in the ICF.  Patients should clearly understand that their participation is voluntary.  They always have the option to leave a clinical trial at any time for any reason.  There should be no pressure to participate in a clinical trial and patients should expect to receive the current standard of care available.

Our Call To Action 

Specifically, on behalf of my fellow patients, here is our call to action to pharmaceutical sponsors. 

1. Incorporate the voice of patient experts in co-creation.  Experts should provide ‘the patient voice and insight’ into the development of patient facing materials and  explore opportunities to reduce patient burden.  Our experience and insight is invaluable throughout the development of new treatments and companies should seek to partner with patient experts. 
2. Train physicians to communicate with patients about treatment options, including clinical trials.  Help physicians and patients find ‘the best’ clinical trials for the individual patient – trials that are medically relevant, inclusive and accessible.   
3. Invest in infrastructure to better leverage technology driven opportunities to support decentralized clinical trials and improve the patient journey.  
4. Update the  informed consent process.  The goal should be to provide the information and context to allow patients to make a truly informed decision.  Develop patient-facing materials that use language that is easily understandable, better graphics and visuals, and a balanced articulation of benefits and risks. Including non-medical risks. 

There are clearly opportunities to further improve the patient journey, to be even more patient-forward in designing and delivering clinical trials.  For many patients, clinical trials provide a ray of hope that otherwise might not be available.  The ICF serves as that bridge to the possible.  

It’s time not just to be informed, but for patients to be empowered to make an Informed Decision.