Success In HIV Treatments Creates Additional Challenges For Drug Developers

By Ed Miseta, Chief Editor, Clinical Leader

Today, there are several highly effective treatment regimens available for HIV patients; however, unmet medical need still exists. One goal of the life sciences industry has been to make the regimens simpler, and some treatments now require just one pill per day. More importantly, the potency and tolerability of many newer antiretroviral therapies (ARTs) have improved dramatically.

"These changes also have set a new bar for drug developers,” states Michael Robertson, executive director and section head for HIV and HCV at Merck Research Labs. “Patients and physicians expect any new treatments to have simple regimens that are both highly effective and well-tolerated. Another big change is patient access. Twenty years ago, patients could only access these treatments by taking part in a clinical trial. Today, patients in the numerous countries across the globe have access to these treatments without having to take part in a study.”

ADVOCACY GROUPS PUSH RESEARCH FORWARD

HIV advocacy groups have been very vocal about how the industry can create better products and have had a strong voice in the desired outcomes of those medications. They are getting their message out via the internet, publications, documentaries, and in person. At one time the groups may have seemed adversarial, but today there is more of a realization that everyone is working toward the same goal.

“People living with HIV are very well educated about their disease,” says Melissa Shaughnessy, principal scientist, clinical sciences and study management — infectious disease and vaccines at Merck Research Labs. “They understand the disease and what treatments are available to them. They also advocate very well for themselves as a community. For that reason, pharma always has been very careful with its trial designs.”

With the treatments currently on the market, it is even more important for pharma to make HIV studies as convenient as possible for patients (i.e., patient-centric). Robertson believes the interactions go both ways — pharma is helping patients understand where the research stands, and patients are helping companies understand where they should be in development of solutions.

SUCCESS BRINGS ADDITIONAL CHALLENGES

Although access to new treatments is good news for patients, it also presents a challenge to researchers. If patients can access these medicines through pharmacies, they no longer have the incentive to take part in clinical studies. After all, patient recruitment is already a difficult hurdle in most trials.

Addressing this challenge, Shaughnessy explains, “If patients no longer need to enroll in a trial to get access to these treatments, that’s something we absolutely must think about when selecting clinical sites and countries.”

To overcome this challenge, sponsor companies must often conduct HIV trials in countries where patient access to these medicines is more limited. Shaughnessy believes trust also plays a large role in overcoming the patient recruitment challenge. Investigators recruit patients for trials, and advocacy groups are also instrumental in recommending trials to their members. Pharma companies must be trusted by both in order to overcome recruitment challenges.

“We take these relationships very personally, as they allow us to target those areas and patients that will best help us to conduct the research. Even in areas where treatments are available, we believe our relationship with experts in the field will assist us in finding the right patients for our studies,” states Shaughnessy.

STEPS TOWARD GREATER PATIENT-CENTRICITY

One theme Merck hears from patient communities is the need to make trials more patient-centric. Many individuals infected with HIV come from vulnerable populations. They often don’t have access to good insurance plans and luxuries often taken for granted, such as reliable transportation. Providing services these individuals lack is one of the ways sponsors can build trust and encourage trial participation. Companies are also working to reduce the number of inclusion and exclusion criteria that will prevent some patients from being able to participate in trials.

Taking trials to the patient, as opposed to forcing them to travel to trial sites, is one effort that is having a profound impact on study participation. Another option is ride-share services that can help with transportation. Based on patient feedback, Merck also is working to simplify the paperwork involved with getting patients enrolled in trials.

For those patients having difficulty making it into sites, Merck is investigating using home healthcare nurses who can visit patients in their homes. The company is also working with sites to add additional hours in the evening and on weekends for patients to visit. “We are even looking into things such as whether patients might require child care services to enable them to visit a clinic for their appointment,” says Shaughnessy. “If a suggestion is made by a patient or advocacy group member, we will look into it to determine the feasibility of the idea. Our goal is to try to eliminate any hurdle that could potentially prevent a patient from participating in a study.”

"If patients no longer need to enroll in a trial to get access to these treatments, that’s something we absolutely must think about when selecting clinical sites and countries."

MELISSA SHAUGHNESSY, principal scientist, clinical sciences and study management – infectious disease and vaccines, Merck Research Labs

INTERNATIONAL TRIALS CREATE CHALLENGES

Helping patients understand how their trial participation will benefit other patients is another way to build trust. If poor, underdeveloped countries are one area where pharma can recruit for HIV trials, Robertson believes there needs to be an understanding that patients in those countries will have access to the treatments after they are developed. Pharma must erase the perception that any treatments developed will be made available only to rich countries, a situation which has occurred in the past. Through a variety of mechanisms, new drugs are now making their way into low-income countries. Programs within pharma companies are assisting with that effort, as are government programs providing funding for these medicines. Organizations such as the WHO, The Global Fund, and the Bill and Melinda Gates Foundation are also providing funds to assist with this effort.

Although there are many similarities to performing trials in the U.S. and other countries, there are also differences that exist. In the U.S., many trials are conducted at large hospitals and university-based medical centers. However, Merck is trying to do more in the smaller, remote, and community-based clinics that are found across the country. Some of those clinics resemble what might be found in low-income countries where patients are generally not located in large, urban areas.

“One of the fundamental things we have learned over the years is that HIV care and research are moving out of the big university clinics,” says Robertson. “We are a large, U.S.-based company, so we have to rely heavily on our staff in other countries to help us locate those smaller clinics that have access to patients. We have staff in countries around the world, and we rely on those staff members to tell us what recruitment and patient-centricity efforts matter most to patients in those areas. There is no one-size-fits-all plan. What works best for the patients at one site and in one country may not be what works best for patients in another location or country.”

This effort to reach physicians at remote sites (both in the U.S. and overseas) is not simply to increase recruitment numbers. Those physicians will be the same ones who prescribe the treatments, treat the patients, and familiarize them with the medications they’re taking. For that reason, Robertson believes working with them is vital.

“Twenty years ago, there were specific places we visited to treat HIV patients,” adds Shaughnessy. “These clinics understood HIV and the complicated regimens that had to be administered to patients. They also performed complicated laboratory tests on patients. Today these tests are much more common, and the regimens are more easily managed. This has eliminated the need for patients to go to these specialty centers and opened the door for them to be treated at smaller clinics. This is an exciting development because it will allow us to help patients who in the past may not have had access to the experts in the large clinics.”