dry eye

Walk a Mile… in Whose Shoes?

How do you manage the dry eye patient who enrolls in clinical trials?

Kelly Nichols, O.D., M.P.H., Ph.D.

Unlike Dr. Bloomenstein and Dr. Mastrota, my day starts with coffee at home in a cup not as precisely measured as your local Starbucks (or java alternative). Also, I don't have a dry eye clinic, at least not in the normal sense of the word. My colleagues and I run an ocular surface research center, and our "patients" are those individuals willing to participate in clinical research and clinical trials.

It takes all kinds of patients

As I write this, the federal government's registry of clinical trials, at http://clinicaltrials.gov, lists more than 97,000 trials in 174 countries. A total of 97 active registered trials in dry eye are taking place across the world. At any given time, our research center has a number of studies running concurrently. These include:

► clinical trials of potential dry eye or ocular surface disease therapeutics at varying stages in the FDA-approval process;
► contact lens studies;
► contact lens solutions studies;
► National Institute of Health (NIH)-funded or biological studies investigating mechanisms involved in ocular surface disease.

Patients present to our clinic for either single-visit or multi-visit studies, but in every instance we have the pleasure of listening to each story of "disease."

The client is always right

Our clinic manager interfaces with Ohio State University for issues concerning regulation (i.e., the Institutional Review Board), grants management, contract set-up and maintenance and purchasing. More importantly, she is closely involved in patient recruitment and retention — both critical elements of a clinical research project.

When she gets busy, she reverts to her "past life" in social work by calling the patient a "client." In my business, the "client" or "patient" is always right, and in our case, the "client" or "patient" has often been the victim of at least one wrong — the lack of appropriate (or any) dry eye management. Doesn't every client, or patient, deserve more?

Through clinical research, our goal is to try to evaluate new products or therapeutics aiming for FDA approval with the hopes of expanding our "toolbox" of options and, ultimately, improving patient care.

Our clinical environment is different than the typical practice — we examine patients the same way each time, as this uniform approach is needed in order to follow a clinical research protocol. In doing so, we see many patients across the range of dry eye severity. Although some of these patients have received treatment previously and others have not, they possess one unifying factor: These patients all have symptoms that impact the quality of their lives. We hear it every day, and each day the story is told in a slightly different way, but with striking similarity. Dry eye patients "feel" their eyes. Some more than others. Some, begrudgingly, can manage it, while for others the "dryness, grittiness, and irritation" is unbearable.

Motherhood and apple pie

I walk through the Arthur G. James Cancer Hospital on my way to the bank. In its lobby, a large sign displays an elderly grandma-looking patient holding an apple pie. The logo beneath this image reads, "Why should you volunteer for a research study? Ask your doctor."

The sign sums up clinical research — patients who volunteer for clinical studies are different from their non-volunteering counterparts, and it does have something to do with the "give a little back" concept — that, or because patients love our mediocre coffee and parking challenges inherent in university life.

Kidding aside, about 85% of volunteers participate in a study to help find a cure or to advance science, according to the Harvard Health Publications website.

In her shoes

SK is one of our clinical research patients. She has participated in several studies, one of which was a randomized, controlled, clinical trial. SK, like most of our patients, had several questions about her participation in clinical research studies.

"How might this new therapy benefit my dry eyes?" she asked.

Even though she is aware that she has a 50% chance of getting randomized to the placebo arm, she is optimistic she will be assigned the new therapeutic agent.

"Are there negative side effects?" she asked.

This is an excellent question. From our standpoint, thorough discussion and informed consent is critical to maintaining a patient throughout the duration of the study.

Careful understanding of the proposed mechanism of action of a potential therapeutic agent is imperative for clinicians involved in a clinical research study, as this understanding enables them to explain the therapy to the patient and discuss potential side effects that may occur as part of a study.

In general, patients must know the details of :

► study conduct
► inclusion and exclusion
► risks/benefits
► study outcome and length
► costs or reimbursement
► study sponsor

In most instances, patients are happy to become involved in clinical trials because they believe their participation will help answer a question about the condition or will help a new therapeutic come to the market — both of which will benefit other patients just like them.

Some instances exist in which the patient in the placebo group experiences worsening symptoms through the course of the study, or experiences an adverse event. Paramount in a clinical trial is the option for the patient to quit the trial, at any time, without prejudice or any impact on his/her future care. When these unfortunate events occur, patient communication is very important.

Equipoise

From a clinician standpoint, clinical equipoise is the hallmark of clinical research. Clinical equipoise means that genuine uncertainty exists regarding whether a treatment will be beneficial — whether it be a new therapy or an off-label treatment which hasn't undergone FDA approval for a new indication. Equipoise impacts "patient" recruitment and enrollment in that no preferential "group matching" of patients is permitted.

Say, for example, that a clinician thinks treatment X works, and that his/her favorite patient would benefit from the therapy. By purposely assigning the patient into one group vs. another, the clinician could influence the study results.

Clinical trial design generally overcomes such influence by using a double-masked approach: Neither the doctor nor the patient is aware of which treatment will be assigned to the patient. This is only possible, however, if the placebo is very similar to the treatment (e.g. same bottle, same viscosity, etc.). The potential for influencing a trial is reduced if the doctor truly has uncertainty regarding the effectiveness of the agent. That said, maintaining a non-biased opinion can be a challenge in today's pharmaceutical environment, where drug companies pay for an increasing share of clinical trials.

After the study ends

SK didn't have an eye doctor, so we referred her to one of our local doctors after the study. We make every effort to return patients to their practitioner after our studies end, if possible. Given that, patients do have a different frame of reference regarding their disease after a clinical trial. While most patients never find out which treatment they received in the study, most have a definite opinion whether they received the drug or the placebo. On a few occasions, we have had to unmask a patient assignment after the study ended. Often, to our surprise, we discover that even though the patient "knew for sure" she was in the drug group or the placebo group, she was mistaken.

Patients learn about testing and research during trials. As a result, they are much more knowledgeable about the specific testing and test findings associated with their condition and are often more involved and motivated in their management plan than before when they return to clinical care.

In all our shoes

Clinical research is a partnership between the patient, the doctor, the staff and the funding agency. If a new drug is involved, misconceptions and bias can easily occur, so communication and directions are critical — not unlike clinical practice.

The similarities between a research center and clinical practice don't end there. Instead of electronic medical records, we worry about electronic data capture. Instead of insurance paperwork, we detail source documents and regulatory documents.

But the unifying element is, of course, the patient. And like Dr. Bloomenstein, I agree — every encounter in our lanes is a medical opportunity to achieve the end point of excellent quality. In our case, the end point of excellent quality is high quality research that will ultimately result in improvements in patient care. I'll walk that walk any day. OM