Introduction: Interpreting Oncological Study Publications
What you Need to Know...
A methodologist’s insight
The handbook begins with the starting point for cancer: risk factors. A cancer clinician may be less concerned about risk factors than practitioners and policy makers working in public health and the prevention of cancer. However, it is important that they understand studies investigating risk factors if they are to discuss the possibilities of the patient developing a second cancer and to provide advice to the patient, family members and others who wish to reduce their cancer risk. This issue also allows us to introduce the reader to the classic designs of epidemiology: cohort and case-control studies.
Next, we tackle the research on identifying effective ways to screen for cancer. Early diagnosis of tumours and, therefore, the opportunity to start treatment early, can lead to improved survival and may avert cancer deaths. But screening can also have adverse effects, cause harm and use up resources. We discuss how the relevant research is done to enable the reader to engage in decision making about the implementation or modification of population-level screening.
The chapter on cancer prognosis focuses on the research that can help to predict a patient’s life expectancy after being diagnosed with cancer. It provides a guide to the interpretation of the findings for various methods of assessing prognosis and possible biases. It leads onto a chapter which shows how reports from population-based registries might be used when making decisions about cancer.
The next chapters bring the reader into the realm of cancer treatment. We begin with the types of research used for drug development, to identify drugs that might go on to be tested in late-stage clinical trials.
Randomised trials are the fundamental study design for comparing the effects of a new treatment with those of current practice, or for comparing multiple treatments simultaneously. However, to provide information on both the beneficial and harmful effects in ways that will help clinicians and patients make well-informed decisions, researchers need to pay particular attention to the choice of outcomes for their clinical trials.
Having measured these outcomes, researchers need to use appropriate methods to analyse them. This handbook includes a guide to some basic concepts around commonly-used statistical methods, knowledge of which is essential when interpreting the reports of cancer studies.
Finally, when trying to cope with the vast amount of research into the effects of treatments for common cancers, clinicians are likely to need to rely heavily on systematic reviews. These reviews help avoid the biases that might come from focusing on the findings of a single study and maximise the power of existing research by providing a summary of what might be a very large body of research. On the other hand, for some cancers, studies are likely to be small and few. The challenges of clinical research in rare cancers can mean that treatment is commonly based on insufficient evidence. Therefore, the penultimate chapter discusses the interpretation of current research and describes novel approaches for trials that are most appropriate for rare cancers.
We conclude with a discussion of pathways that clinicians might follow if they would like to become researchers themselves and become providers of the high-quality research evidence that is needed to understand cancer better and to treat the disease more effectively.
The handbook can be read from beginning to end, or a clinician might choose to read specific individual chapters when considering a particular issue. We hope that all readers will find that the handbook helps them use research as part of the evidence base for discussions, decisions and choices about the care of patients with cancer.
Mike Clarke, DPhil
Why You Need to Understand It
The oncologists’ perspective
The definition of clinical benefit is also changing. In the past, improvement in overall survival (ideally accompanied by a perceived improvement in quality of life) was regarded as clinical benefit. But due to the increase in the number of sequential treatments, endpoints such as progression-free survival are now frequently regarded as surrogate markers of clinical benefit. Another worrying issue is the threat of publication bias: good news sells better. The chance of a manuscript being published is higher, as well as the chance of a big podium at a scientific congress. Furthermore, 79% of trials registered in the European Clinical Trials Database (EudraCT)* are commercially funded by an industry which sells products.
Due to these phenomena, each practising oncologist should refrain from passively absorbing the flood of new scientific information. This handbook enables all of us to read between the lines of a scientific publication and to better estimate the true benefit of a new oncological intervention. In this way we can better find the balance between treatment benefit and treatment hazard for our patients and keep cancer care affordable.
We are indebted towards Professor Mike Clarke, a great and enthusiastic teacher, who was willing to coordinate the scientific content of this handbook.
Please enjoy reading and learning.
Henk van Halteren, MD
Veronika Ballová, MD