This week, LymeDisease.org submitted comments on the proposed National Institutes of Health’s Tickborne Diseases Strategic Plan (NIH Research Plan).

We reached out to the Lyme community to hear your views about it. Over 4,300 Lyme disease patients responded to our survey in a two-week period. Those responses helped shape our comments to the NIH.

Here are some of the points we made:

I. NIH should emphasize research for diagnosis and treatment of late and chronic Lyme disease. It should also seek ways to reduce treatment failures for early Lyme disease.

The NIH plan identified five research areas. We asked patients to tell us which were the most important to them. Patients said that diagnosis and treatment should be at the top of the list.

Diagnosis and Detection Therapeutics Basic Research Prevention Resources

Patients also said that the most urgent priorities should be diagnostic and treatment approaches for late/chronic Lyme disease. Patients also believed that better treatments were needed for acute Lyme disease, to prevent the disease from progressing to chronic Lyme disease. Our specific recommendation is below:

Recommendation: Diagnosis and treatment should be the top priorities in the research strategy and both of these areas should dedicate a significant portion of their efforts toward late and chronic Lyme disease. We also need to develop more effective treatments for early Lyme disease to prevent the development of chronic Lyme disease.

II. NIH should increase funding for Lyme disease research

Lyme disease is the number one reported vector-borne disease in the United States. According to CDC surveillance data, 36,429 cases were reported in 2016 compared to 96,075 total cases of vector-borne disease. (CDC MMWR 2018)

But while Lyme disease accounts for 38% of the total case counts of vector-borne diseases, it receives only 4% of the funding allotted to vector-borne diseases: $21 million compared to $534 for vector-borne diseases. (NIH Funding Estimates 2018) We recommended that Lyme disease funding be increased to 38% of total vector-borne disease funding, to be commensurate with the magnitude of the disease burden.

III. NIH research grant-funding panels should include patients with chronic Lyme disease and their treating physicians. Patient representation should not be token.

To ensure that research priorities are patient-centered and reflect the needs of patients with chronic Lyme disease and the physicians who treat them, decision-making groups should include representation of both patients and physicians to select and prioritize research funding decisions. Almost all survey respondents regarded the need for patient (96%) and physician representation (98%) on NIH research funding groups as either extremely or very important.

Respondents regarded having lived experience with chronic Lyme disease (either as a patient or caregiver) as a fundamental requisite to be able to provide meaningful representation. A majority also believed that representatives who were nominated, vetted, or supported by widely recognized patient advocacy groups deemed trustworthy by the community would provide meaningful representation.

In contrast, respondents regarded as token representatives people who have no lived experience with chronic Lyme disease, applicants objected to by the community, or those who only had experience with acute disease. We also emphasized that it is important that there be two or more representatives to guard against tokenism.

IV. The NIH Research Strategy should include innovative research approaches, such as big data, real world research, precision medicine and patient-driven registries like MyLymeData

The Promise of Big Data, Real World Research, and Precision Medicine. There is a growing recognition that the traditional clinical trial research model is inefficient. The few NIH-funded clinical trials in chronic Lyme disease utilized very small samples (ranging from 37 to 129), took 2.5 to 5 years to complete recruitment alone, and excluded 89-99% of the applicants. Trials this exclusionary are not generalizable to the population seen in clinical care.

Moreover, they do not address the goals of precision medicine, which seek to identify the specific treatments most likely to improve the health outcome for the individual patient, given his/her unique circumstances and presentation.

Today, innovative research approaches, including our MyLymeData patient registry and research platform (which has enrolled over 12,000 patients), seek to accelerate the pace of research, make it more patient-centered, and develop a learning system of healthcare where research findings are informed by and implemented into real world clinical practice rapidly.

MyLymeData is part of the patient-centered research movement that aims to transform the traditional research hierarchy in which studies are conducted on passive patients into a partnership model between patients and researchers.

Unlike traditional trials, patient registries are uniquely suited to:

Evaluate care as it is actually provided in real-world practice,

Assess complex treatment patterns and treatment combinations, and

Evaluate patient outcomes when clinical trials are not practical or are difficult to conduct (for example, when long-term outcomes are important).

This approach is attractive because it advances co-creation of research, promotes patient-centered methods, and develops research capacity. Over 90% of respondents to our survey believe the NIH Research Strategy should include real world patients, big data techniques, and patient registries like MyLymeData.

V. NIH funding research in chronic Lyme disease should be in partnership with the Lyme community

Another survey of ours, on stigma and privacy in Lyme disease, showed that Lyme patients face a remarkable amount of stigma and discrimination. Some NIH-funded research studies have been used to dismiss or diminish patient concerns. (e.g. Klempner 2001)

They also have harmed the community by further stigmatizing or marginalizing its members and making it more difficult for patients to obtain care. Almost all NIH survey respondents stated that it was important to increase patient engagement in determining research priorities, research funding and research design and implementation.

There is an approach to research that actually includes patients as partners. It is called Community Based Participatory Research.

Its goal is to provide partnerships between the community and researchers that can strengthen academic–community relationships; ensure relevancy of research questions; increase data collection capacity, analysis, and interpretation; and minimize the negative or stigmatizing effects of research on the partners.

Community Based Participatory Research promotes the establishment of long-term research relationships to pursue on-going studies and accelerate the research enterprise. When combined with big data and precision medicine, this approach is the most promising to accelerate research in Lyme disease.

VI. The term “Post Treatment Lyme Disease Syndrome” should be abandoned.

Approximately 60% of respondents to this survey disapproved of the terminology “Post Treatment Lyme Disease Syndrome” (PTLDS) to characterize patients who do not improve with short-term treatment protocols.

The term PTLDS was first proposed in Table 5 of the 2006 Infectious Disease Society of America (IDSA) guidelines. We believe this definition reflects the fact that the guideline panel consisted exclusively of researchers. (Wormser 2006)

PTLDS is a narrow, exclusive research definition that has been misapplied to clinical care under the IDSA treatment guidelines, resulting in many patients being denied care.

Prior to the introduction of the term PTLDS in the IDSA guidelines, a 2006 CDC study used the term “late/chronic Lyme disease” to describe this subset of patients. (Zhang 2006)

Research definitions used to recruit patients for NIH clinical treatment trials for chronic Lyme disease excluded between 89-99% of those who applied. Research definitions this exclusionary should not be applied to clinical care.

We asked patients to rank four terms that are commonly used to describe this subset of patients. Chronic Lyme disease topped the bill, while Post-Treatment Lyme Disease Syndrome was the least favorite.

Chronic Lyme disease (3.20) Persistent Lyme disease (2.85) Treatment-resistant Lyme disease (2.27) Post-Treatment Lyme Disease Syndrome (1.72)

Survey takers were also given an option to suggest an alternative to these terms. Many suggested the term “late Lyme disease,” which is reminiscent of the prior CDC nomenclature.

We recommended that the term PTLDS be abandoned because it harms patients’ ability to receive clinical care.

Patients with symptoms persisting six months following a brief antibiotic course should be referred to as having “chronic Lyme disease,” “late Lyme disease,” or “late/chronic Lyme disease” to avoid clinical harm caused to patients when research disease definitions are conflated with clinical care criteria.

You can read the entire submission that we made here: NIH Lyme research comments

Lorraine Johnson, JD, MBA, is the Chief Executive Officer of LymeDisease.org. You can contact her at lbjohnson@lymedisease.org. On Twitter, follow her @lymepolicywonk.