Biomedical research and dissemination: The value of global collaborations.

Background

This is the inaugural issue of the Journal of the National Cancer Center (JNCC), a journal designed to appeal to the international community of health professionals and researchers across the full spectrum of cancer research. One of its goals is to contribute to cancer research dissemination and cancer care around the world. We offer this Perspective to emphasize the importance of international collaborations in cancer investigation and in the timely dissemination of research findings. We also describe examples of our own ongoing cross-country collaboration as members of a team of Chinese and U.S. investigators.

History has long ago proven that exposures to disease-causing factors are rarely confined within international borders, and we forget these lessons at our own peril. The easiest examples that come to mind are infectious in nature: bubonic plague, smallpox, Ebola, and of course the COVID-19 novel coronavirus pandemic that has been recently raging around the world. However, non-microbial exposures can also “infect” societies around the world, driven by trade patterns, spreading industrialization, economics, and adoption of components of lifestyle, bringing with them chronic disease and public health epidemics such as cancer. Obvious examples are the epidemic of tobacco use, convergence of global diets, or the changes in physical activity and air quality that come with automobile sales and industrial growth, in turn associated with increasing risk of lung, colorectal, or breast cancers in countries where rates were previously low. Population age structures also differ and are changing internationally and with them national risk patterns, given that cancer is a disease of aging. For these reasons alone, public health professionals can learn from exposure/disease trends in other countries and use these lessons to improve health or avert epidemics in their own countries.

Differing disease patterns among countries may also yield important biological insights. For example, reports of lung cancer in Asian women who had never smoked led to the observation that these women had a relatively high prevalence of EGFR (epidermal growth factor receptor) mutations and ALK (anaplastic lymphoma kinase) rearrangements in their non-small cell lung cancers. In turn, this lead had important therapeutic implications. Never smokers with these genetic mutations showed favorable responses to tyrosine kinase inhibitors.

But there are additional reasons why every country can learn from other countries. Although disease-causing exposures may spread rapidly across international borders, healthcare delivery systems are often more static within each country. In addition, each country has its own distinct medical culture. A clinical intervention that has shown success in one country may yield additional lessons within a very different medical cultural setting. For example, acceptance of cancer screening tests or preference for specific tests may vary internationally among health professionals and the public. Policymakers in different countries may also want to see that a given screening test is of benefit in their own population before incorporating it into their healthcare system.

Cancer information dissemination: physician data query (PDQ®) translation

Communication of important findings from cancer clinical investigation to health professionals and the public is a critical element of translating research findings into health benefits. For that reason, the National Cancer Act, which created the U.S. National Cancer Program in 1971, emphasized that goal in the mission of the National Cancer Institute: “The Director of the National Cancer Institute shall…collect, analyze, and disseminate all data useful in the prevention, diagnosis, and treatment of cancer, including the establishment of an international cancer research data bank [ICRDB; later to be named PDQ] to collect, catalog, store, and disseminate insofar as feasible the results of cancer research undertaken in any country for the use of any person involved in cancer research in any country.” Note the explicit international scope of the PDQ resource from inception. Over the subsequent years, the PDQ developed online evidence summaries written by its six editorial boards, which meet 4-8 times per year and regularly update the information in response to emerging medical literature: Adult Treatment, Pediatric Treatment, Supportive and Palliative Care, Screening and Prevention, Cancer Genetics, and Integrative Therapies. Evidence summaries are provided in both health professional and patient versions. In addition, the PDQ resource includes, three dictionaries (cancer terms, genetics terms, drug terms), a library of biomedical images, and a collection of brief summaries on drugs currently used in cancer treatment.

Evidence summaries are provided by NCI in English and Spanish, and selected PDQ content is made available in Japanese and Arabic through international collaborations. This facilitates adaptation of PDQ information by other countries to their healthcare settings. The most recent addition is the ongoing translation into Chinese, with dissemination of content by the National Cancer Center of China. That translation arose from the very first meeting of two authors of this paper (BSK and JH), a meeting that led to the collaborations described in this paper. The translation of PDQ into Chinese is filling an important gap by making this evidence-based cancer information available in China, which comprises nearly 20% of the world's population. The official launch of first phase of the Chinese PDQ occurred on June 26, 2016, and a new NCC website with updated PDQ information will be launched in the near future.

Research collaboration with international impact

A second area of our collaboration between China and the U.S. is work on cancer screening trials. There is a long history of collaboration on cancer prevention and control trials of international importance between China and the NCI. For example, a randomized trial conducted in Linxian province of several vitamin/mineral combinations showed a reduction in cancer rates associated with the combination of beta carotene, vitamin E, and selenium; and a community-based study in rural China showed a reduction in esophageal mortality associated with screening. Ideally, trans-national clinical trials address questions that are of relevance to each country; and that is the case with our ongoing collaboration on screening for lung cancer and for colorectal cancer that we describe here. With respect to lung cancer screening, several randomized trials have shown the efficacy of low-dose computed tomography (LDCT) in screening people of elevated risk of lung cancer due to cigarette smoking. The first and largest was the National Lung Screening Trial, which compared annual LDCT to chest X-ray. , Smaller randomized trials of LDCT showed similar results. , However, all were conducted in Western populations, with few or no Asians or Asian women and virtually no never-smokers. The investigators at National Cancer Center of China (NCC) recognized the need to obtain direct evidence in their own healthcare delivery system about the potential benefits and harms of LDCT, including Chinese women with risk factors for lung cancer other than active smoking, and in their own healthcare delivery system before incorporating routine lung cancer screening into national policy. Beginning in 2012, they have been working with their U.S. NCI counterparts who conducted the NLST. An initial feasibility study was designed and conducted in three urban screening centers chosen to represent low, moderate, and higher income cities (Chinese Clinical Trial Registry no. ChiCTR-IOR-15007160). A total of 2,696 participants were randomly assigned to one of three study arms: annual LDCT, biennial LDCT, and a control arm. This randomization is of obvious value to China healthcare policy. But it also addresses a very important unanswered question of relevance to U.S. healthcare policy, the relative benefits and harms of LDCT screening every year versus every other year. There is no existing direct comparison of these two screening intervals in a trial powered to detect lung cancer mortality differences, and such a trial is not feasible in the U.S. Both countries therefore benefit from the collaboration.

The jointly designed feasibility study was particularly efficient, providing additional information of value to both countries. In what is termed a reciprocal control design, randomization into the three lung cancer screening study arms also included concomitant assignment to one of three colorectal cancer screening strategies: one-time colonoscopy in arm 1, annual fecal immunochemical test (FIT) with OC-Sensor (OC-FIT) in arm 2, and annual Insure-FIT plus a Septin 9 blood test in arm 3. The now-completed study has shown that the trial is feasible, including participant recruitment and retention (manuscript in preparation). A large definitive trial to enroll over 100,000 participants in three arms across 18 provinces in China has been launched that incorporates lessons learned in the feasibility study, including omission of the Septin 9 blood test from the third arm of the study (Chinese Clinical Trial Registry no. ChiCTR1900025257).

Summary

Public health is a global issue, and widespread dissemination of biomedical research results is therefore of benefit around the world. In addition, collaboration on studies can provide answers to clinical questions of importance to multiple nations, including some that are not even feasible to address in individual countries. This requires international teams that work together and learn from each other on projects of import to each of their countries.

Of importance, the collaborations described here all resulted from ideas generated by Chinese and U.S. investigators looking for innovative approaches to research and communication needs in cancer, rather than simply responding to the needs of policy makers in either country. It is therefore intended to be a fingerpost for future collaborations. Given the international scope of this journal, the authors are pleased to provide this perspective on behalf of all of our Chinese and American colleagues for this inaugural issue of JNCC.

Declaration of Competing Interest

The authors declare that they have no conflict of interests.