Jan 1, 1970 - Jan 1, 1970,

Patients’ Week 2011: CER and the case for active patient engagement

Nathalie Horowicz-Mehler and John J Doyle explain why comparative effectiveness research (CER) must include patients’ perspectives on how to balance risk and benefit

Comparative Effectiveness Research (CER)—defined by the Institute of Medicine as the “comparison of effective interventions among patients in typical patient care settings, with decisions tailored to individual patient needs”—plays an increasing role in the commercialization of new products.

A recent studyfound that over the past decade, 51 percent of new molecular entities (NMEs) had CER data available at the time of US approval, including 89 percent of products for diabetes, 73 percent of those for infectious diseases, 64 percent of those for HIV/AIDS, and 35 percent of those for cancer.

Going forward, continuing demand for CER from payers, patients and providers will drive biopharmaceutical companies to view innovation from the perspective of a broad range of stakeholders—all requiring real-world data on safety, patient outcomes, and product value.

Healthcare consumers—patients and their providers—face complex choices among various therapies and interventions.

Groups that initiate collection of CER data, who may represent industry, government or payers, should take four elements into consideration to generate robust evidence that will enrich clinical decision-making:


1.    Engagement of patients in the CER study design process to ensureidentification of the healthcare outcomes that patients value;

2.    CER studies conducted in patients with multiple chronic conditions and varied ethnic backgrounds to reflect real-world patient populations;

3.    Timely access to the latest CER evidenceby patients and their physicians at the points of healthcare interaction to support medical decision-making;

4.    Awareness of non-clinical considerationsthat may influence the decision-making process, such as the relative out-of-pocket costs of therapies that might impact medication adherence and ultimately health outcomes.


Availability of robust evidence


Worldwide, many government bodies are involved in generating comparative effectiveness data, such as the UK NICE, the German Institute of Medical Documentation and Information (DIMDI), and the Canadian Agency for Drugs and Technology in Health (CADTH).

In the United States, the Patient-Centered Outcomes Research Institute (PCORI), established by Congress through the 2010 Patient Protection and Affordable Care Act, will be an important player in generating CER evidence.

PCORI will “commission research that is responsive to the values and interests of patients and will provide patients and their caregivers with reliable, evidence-based information for the health care choices they face.”

Patient engagement in the design of CER studies is paramount to ensuring that primary and secondary outcomes meaningful to patients, be they short or long-term, are included in the study protocol.

Including therapeutic options that are based on the choices patients face is another integral component to ensuring relevance of study findings.

While newly diagnosed patients (inception cohorts) are often preferred for CER studies to minimize bias, such patients are not in a position to identify optimal outcomes for a disease.

Instead, patients with a history of managing the disease and its treatment might be better positioned to comment on the strengths and weaknesses of therapies as well as ideal and realistic therapeutic goals. (For more on involving patients in study design, see The use of adaptive designs in clinical research, Patients and medical devices: Patient-centric by designand Making patients part of the pharma conversation .)

The benefits and harms of any treatment may also evolve over time, as people age and develop additional conditions requiring therapy.

Current treatment studies rarely last more than five years; there is a need for changing responses to treatment to be assessed in CER through longitudinal outcomes studies.

The addition of concomitant therapies may also change the risks-benefit profile of a given agent and should be incorporated into real-world research.


Studies in patients with multiple chronic conditions


To achieve its objectives, CER must reflect the experience of patients with multiple chronic conditions, a population that accounts for more than 80 percent of Medicare costs in the US and is overrepresented in Medicaid and private insurance plans. 

To accurately inform decision making for patients with multiple chronic conditions, CER must include large, diverse populations representative of those cared for in clinical practice, focus on broader health outcomes than clinical research generally considers, and compare interventions that have benefits for multiple health conditions or for overall health.

Treatments that are effective for one disease may exacerbate other diseases or adversely affect overall health.

The likelihood of such mixed benefits and harms increases as the number of coexisting conditions mounts.

As a result, there is a need to focus increasingly on cross-disease, “universal” health outcomes in research and clinical care, such as the burden from symptoms such as fatigue.

However, opening the study of therapies to broader, more naturalistic patient populations risks clouding the true effect of the drug,since these patients have co-morbidities whose therapeutic path might intersect with the therapy under evaluation.

This is a fundamental issue in bridging the gap between the population-level study of drug effects and applicability at the individual patient level.

Pursuing effects at the aggregate level offers little insight for daily decision making by patients and their providers.

Only large-scale studies can provide the sample size necessary to enable analyses of sub-groups of interest with a profile similar to that of the individual patient.

The onus is therefore on the public sector to initiate such studies, with funding from both public and private sources.

Indeed, public health has much to gain in promoting the real-world benefits and risks of drugs tailored to multiple patient sub-populations.


The need for timely access to CER evidence


Timely updates are essential for patients to benefit from recent findings.

PCORI has made a commitment to “make sure the results of its research are provided to patients and clinicians in ways that are responsive to their needs and interests … PCORI will ensure that its research is not construed as mandates for practice guidelines or coverage recommendations.”

This could help overcome the fact that the disparate sources of CER evidence generated by payers and government bodies, as well as the complexity of the data (i.e., inconsistent study designs or outcomes assessed), can make it challenging for healthcare consumers to leverage in decision-making.

A centralized repository of the CER evidence generated and real-time manipulation of the data would be ideal.

Such a system would enable a physician and his or her patient to assess evidence applicable to a particular patient profile and situation.

Ideally, access to this data repository would be accomplished at the point of care to support clinical decision-making in real time.


Awareness of non-clinical considerations


When commercializing a drug, the impact of a drug’s out-of-pocket cost on patient medication compliance, persistence, and effectiveness should be considered.

The government-led CER initiative is understandably focusing on the clinical evaluation of drugs.

However, the real-world mandate of CER also means that financial forces cannot be ignored.

Chief among these are the direct cost of therapy to patients via a co-pay or co-insurance, which can impact choice of therapy and medication adherence, despite the strength of comparative clinical evidence.

Indeed, lack of adherence to therapy is linked to decreased therapeutic outcome.

Concretely, this would mean that government should consider working with payers to ensure that coverage and reimbursement is consistent with and supports CER findings.

In conclusion, CER is playing a growing role in enabling market access for new products, and this trend is poised to continue.

The work of bodies such as NICE, DIMDI, CADTH and PCORI will cement CER’s position as a vital, patient-centric aid in clinical decision-making for all stakeholders.

Ultimately, patients need to be more engaged in the process, from input into outcomes assessed in CER studies to larger patient population representation in those studies.

Finally, as end-users of the data generated, patients need to be able to access the most up-to-date CER data in a format that allows prompt decision-making support.

In order to ensure the right patient receives the right drug at the right time, CER must formally incorporate the patient’s perspective on how to balance every product’s risks and benefits.


Nathalie Horowicz-Mehler, M.S., M.Phil., is Principal Consultant and John J Doyle, Dr.P.H., is Vice President and Managing Director, Consulting at Quintiles.


For more on CER, see How to build value through comparative effectiveness research.

For everything patient-related, join the sector’s other key players at Patient Adherence, Communication and Engagement (PACE) USAon October 24-25 in Philadelphia. Download the full PACE agenda and speaker line-up here.  Want to know more? Contact laura@eyeforpharma.com.

To read our Patients’ Week stories from 2010, see Patients’ Week 2010.

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Jan 1, 1970 - Jan 1, 1970,