This chapter explains how health screening began, how the aims have evolved, how evidence and organisation influenced matters, and how challenges in the future will give rise to continuing change. It begins with Gould’s address in 1900 to the American Medical Association and charts events that led, almost by accident, to the institution of comprehensive annual testing of healthy adults in the USA, and to 5 day hospital-based ‘Human Dry Dock’ screening for Japanese executives. Scientific challenge then came from two randomised control trials, which failed to find benefit, but by then screening had become an important commercial activity. Using the UK cervical screening programme as a case study, the chapter explores how the optimism of the 1960s led through disillusionment, then to programme organisation and, by the 1990s, an era of realism. Evolution of the Wilson and Jungner criteria as an aid for policy making is covered. A key challenge now is to ensure best value policy, high quality systematic programme delivery and informed choice in the face of commercial forces that lead to the glossing over of screening’s complexities and far reaching consequences.
This chapter reviews the different ways in which the term ‘screening’ has been and is used, and defines the meaning used throughout the rest of the book. Growth of screening programmes in the twentieth century led to a range of activities which vary widely in purpose and process, from bloodspot tests in newborn babies, through to whole body scans for the wealthy worried well. This chapter explains the different kinds of testing done on healthy people, and how these differ from diagnostic tests for solving problems that patients bring to clinicians. It explains where screening fits in the pathway of disease development. It describes the basic system that makes up a screening programme as opposed to just a screening test. It explains, using infant phenylketonuria as a case history, why screening needs to be delivered as a proper programme if it is to successfully achieve risk reduction. We describe the variation in screening delivery across different countries and emphasise that this book focuses on systematic screening programmes, aimed at risk reduction for the screened individual, based on sound evidence that harm, benefit and affordability are well balanced, and delivered to pre-agreed policy and standards.
Abstract This chapter gives the reader an appreciation of main issues that public health practitioners regularly deal with in screening, and how to approach them. This needs management skills and an understanding of screening programmes. Typical problems include preventing screening from starting when there is no sound evidence base, dealing with provision of poor quality screening, implementing policy changes within existing screening programmes, dealing with legal challenges relating to screening, and coping with damage caused by commercially driven provision of screening tests where there is lack of evidence, lack of informed choice, and no provision beyond the initial test. Dealing with any of these matters can involve using the media, and the final section of the chapter gives advice about how to cope when the media spotlight turns on screening. Prostate cancer and ovarian cancer screening are both used as case studies in this chapter.
This chapter explains why quality assurance is essential if screening is to do more good than harm. It describes some of the history and thinking that has shaped approaches to quality in industry and in healthcare, starting with an example from the American car industry and focusing on two founding fathers of quality - W Edwards Deming, and Avedis Donabedian. It outlines Donabedian’s seven components of quality, and shows how these encompass the notion of best value in healthcare so that efforts are devoted to improving health and social justice. It then goes on to explain some of the ways of measuring screening quality, setting standards and ensuring standards are met. It uses case histories and practical examples so that the reader can easily apply the lessons in their day to day work.
Abstract This chapter gives the reader an understanding of the essential tasks involved in setting up a good quality screening programme. Newborn hearing screening is used as a case study. There is an old saying that all you have to do to create an effective service is choose the right things to do, then do them right. Choosing the right screening involves assessing the evidence and making policy. Doing screening right means setting up a well ordered programme for screening that is of value, ensuring that the service is always of high quality, dealing effectively with problems. It also means making sure that when there is no evidence that benefits would outweigh harms, then screening is vest avoided. Different health care systems have very different ways of planning, delivering, and funding their screening programmes. The chapter focuses on matters that are essential if screening is to achieve public health improvement - irrespective of where, and in what type of health system, it is being delivered.
Abstract This chapter shows how resources, values, beliefs, and commercial factors all influence screening policy, and gives clear insight into some of the ethical dilemmas involved. Case histories include celebrity selling of HPV testing, the USA ‘Mammography Wars’ incident, the Cartwright Inquiry into events at National Women’s Hospital in Auckland in the 1960s and genetic testing. The chapter strongly emphasises the value of following robust and explicit processes when making screening policy, and argues that this is best done at national level. The reasons why screening policy-making can be difficult are explored in detail, and clear lessons are drawn from the case examples. The chapter addresses the technical aspects of using evidence, and also explains the power of the cultural belief that all screening must automatically be a good thing and of commercial, professional and institutional interests, often enacted through invisible lobbying using ‘third party’ techniques. The ethical conflicts inherent within screening are described and explored.
Abstract This chapter gives understanding of measuring evidence about consequences of screening programmes, at a level needed by public health practitioners interpreting evidence for setting screening policy, or for ensuring high quality programme delivery. It takes a practical approach, illustrating with real-life case histories and examples, ranging from infant neuroblastoma to abdominal aortic aneurysm screening. The issues covered are Three Main Biases (healthy screenee effect, length time effect including overdiagnosis, lead time effect); Three Main Evaluation Methods (randomised control trials, time trend analyses, case control studies, and mention of rare conditions); Test Performance (sensitivity and specificity, positive and negative predictive value, receiver operator characteristic curves); Two Additional Sources of Information (pilot or demonstration projects, modelling); Summarising Information on all Outcomes (the numbers in the flow diagram, and decision aids) and finishing with A Note on Sound Science. Careful use of terminology is emphasised, and pitfalls with use of jargon terms (true and false, positive and negative) and misleading labels (early, late, pre-symptomatic, carcinoma in situ) are explained. The issue of overdiagnosis of inconsequential conditions is explained.
Background GBS is the leading cause of morbidity and mortality from neonatal sepsis in the UK and patient groups are keen for screening to be implemented. Intrapartum antibiotic prophylaxis (IAP) is offered to women identified with GBS carriage or GBS risk factors to prevent mother to baby transmission and early-onset GBS disease (EOGBS,<7 days). This review on universal GBS screening for pregnant women was undertaken to assist NSC policy decision-making. Review questions were on: epidemiology of GBS, diagnostic accuracy of tests, effectiveness of IAP treatment, and effectiveness of universal GBS screening. Methods Medline, Embase, and Cochrane databases were searched. Grey literature included Public Health England, British Paediatric Surveillance Unit, Audits and Confidential Enquiries, and reference lists of included papers. Participants were pregnant women≥35 weeks or neonates<7 days. The intervention was selective culture from recto-vaginal swabs at 35–37 weeks followed by IAP treatment for those who were culture positive. Reviewers independently screened records, extracted data, and assessed methodological quality using appropriate tools for each question, including QUADAS-2, Cochrane RoB, and RoBANS tools. Data were synthesised narratively. Results 73 studies were included from 6287 references. EOGBS in the UK affects 0.57 per 1000 live births with a case fatality of 5.2%. Twenty-two percent of EOGBS cases and 63% of deaths are in preterm births (many would be ineligible for screening). The natural history of GBS is not known. We estimate that universal GBS screening would be offered to approximately 7 18 126 pregnant term women annually.Approximately 63 347 (57.7%) women who test positive in labour and 3282 (8%) who test negative in labour would transmit GBS to their neonates, and approximately 350 (0.5%) neonates would develop EOGBS. We estimate the positive predictive value of selective culture to detect EOGBS to be around 0.2% (350/150,806). More than 1 50 450 (>99%) women would be false positive and unnecessarily treated. Harms from IAP are unclear but will include antibiotic resistance and other possible health problems. There were no randomised controlled trials of the effectiveness of GBS screening and observational studies gave inconsistent results for EOGBS mortality and morbidity. Conclusion EOGBS is an important health condition. However, tests are not accurate predictors of maternal GBS transmission, or of EOGBS. Evidence on the harms and benefits of GBS screening is limited. Universal screening is therefore not recommended.
Background Pragmatic integrated trials use routine data and systems to automate participant selection, randomisation, outcome measurements and/or other elements to deliver large trials at low cost. Here we present an example of a large pragmatic integrated trial in breast cancer screening, and discuss the situations in which these trials are appropriate and acceptable. Methods The intervention was a simple change to the mammography test for breast screening. Interpreting whether screening mammogram show cancer is a difficult repetitive task that can result in missed cancers and false-positive recalls, and some studies have indicated that missed cancers may increase with time on task (the vigilance decrement). In the UK two readers independently evaluate each batch of mammograms to search for signs of cancer. The intervention was to change the order in which batches of mammograms were presented for interpretation, to reduce the effects of the vigilance decrement. This was evaluated using a multicentre, double-blind, cluster randomised clinical trial at 46 breast screening centres in England for 1 year. Three hundred sixty readers participated. The primary outcome was cancer detection rate; secondary outcomes were rates of recall and disagreements between readers. Results 1 194 147 women who had screening mammograms were randomised (596 642 in the intervention group; 597 505 in the control group), and 10 484 cases (0.88%) of breast cancer were detected. There was no significant difference in cancer detection rate with 5272 cancers (0.88%) detected in the intervention group vs 5212 cancers (0.87%) detected in the control group (difference, 0.01% points; 95% CI, −0.02% to 0.04% points). There was also no difference in recall rate, with 24 681 [4.14%] in intervention and 24 894 [4.17%] in the control group (difference, −0.03% points; 95% CI, −0.10% to 0.04% points). Patterns of cancer detection and recall with time since a break indicated that performance did not decline with time on task as predicted by the vigilance decrement theory. In fact, positive predictive value increased with time on task. Discussion This pragmatic integrated trial in over 1 million women cost less than £300 k, and demonstrates that in certain circumstances this study design is appropriate. Considerations when planning a pragmatic integrated trial include whether consent is required at the individual or institutional level, whether the relevant outcomes are available in routine data, and the cost of the intervention.
Background Tyrosinemia type 1 is a rare autosomal recessive disorder of amino acid metabolism, affecting approximately 1 in 1 00 000 people. Without treatment, death is common in childhood. Treatment with nitisinone is associated with reductions in mortality and morbidity; some studies suggest better outcomes when treatment is initiated before the symptoms of the disorder present. An apparent benefit of earlier versus later treatment has been used to support the implementation of newborn screening for Tyrosinemia type 1, but these studies have not been synthesised or quality appraised. We conducted a systematic review to examine if individuals treated following screen detection of the disorder had better outcomes than those treated following symptomatic detection. Methods Standard systematic review methods were used. Embase, Medline, Pre-Medline, and Web of Science were searched. Participants were individuals with Tyrosinemia type 1. We compared people who received nitisinone following screen detection of the disorder (early treatment) with those who received nitisinone after symptomatic presentation (late treatment). Any reported outcomes were considered. Two reviewers independently screened and assessed records, and conducted quality appraisal (using the Quality Assessment Tool for Quantitative Studies). Data extraction was carried out by one reviewer, and checked by another. A narrative synthesis of results was carried out. Post-hoc comparisons were conducted to address confounding factors and applicability concerns. Results The titles/abstracts of 470 unique records were examined, and 50 full texts assessed. Seven articles were included in the review. Study sample sizes ranged from 17 to 148. Methodological quality of the studies was moderate to weak. There was evidence of associations between early treatment with nitisinone and lower rates of death, liver disease and transplantations, and renal dysfunction. However, posthoc analyses suggested an association between earlier treatment and lower rates of liver transplantation but not mortality (analysis 1) or no differences in outcomes for those treated earlier versus later (analyses 2 and 3). Discussion Evidence from observational studies suggests that treatment with nitisinone initiated during the pre-symptomatic period may be beneficial to people with Tyrosinemia type 1. However, this is subject to bias and applicability concern; the apparent benefits of early treatment may not be present when these issues are addressed. There are several challenges inherent in rare diseases research, including small and heterogeneous populations, lack of appropriate comparator treatments, and limited knowledge about the disease. Our review suggests that alternative research methods or tolerance of lower levels of evidence may be required.
Background Routine screening for lung cancer in high risk groups (characterised by age and smoking history) is recommended in the USA and may be implemented elsewhere. It is unclear whether being screened for lung cancer promotes smoking cessation or conversely provides false reassurance and a ‘license to smoke’. This study aimed to understand how experiences of lung cancer screening influence individual decision making about smoking. Methods Thirty one people in Scotland, aged 51–74, took part in semi-structured interviews. They had been screened with the EarlyCDT-Lung Test (13 positive result; 18 negative) as part of the Early Cancer Detection Test–Lung Cancer Scotland (ECLS) Study and were long-term smokers when screened. Verbatim transcripts were analysed using thematic analysis. Results Interpretations of test results was a key theme, but were often inaccurate, for example a negative result interpreted as an ‘all-clear’ from lung cancer and a positive result as meaning lung cancer will definitely develop. There was no clear pattern in decisions made about smoking in response to positive or negative test results. Emotional response to those interpretations was an overarching theme in decisions about smoking. Emotions included fear, shock, upset, worry, anxiety, guilt, relief, reassurance and indifference. Other themes included changes in perceived risk of smoking-related disease, a feeling that now is the time to stop smoking, interpersonal family influences and avoidance of thoughts about smoking. Of those who had stopped smoking, some cited screening experiences as the sole reason and some cited screening along with other coinciding factors. Cues to change were experienced at different stages of the screening process and not always immediately following a test result. Some participants indicated they underwent screening in order to try and stop smoking. Others expressed little or no desire to stop. In general, lung cancer screening was experienced as a unique opportunity, which sometimes prompted successful or unsuccessful attempts to stop smoking. Conclusion Lung cancer screening can be a ‘teachable moment’ for smoking behaviour change. Emotional responses to test results, which can be misinterpreted, were an important theme but behavioural responses varied according to the individual. Findings should be considered within the context of a group of predominantly life-long smokers undergoing a novel blood screening test, who might already have increased motivation to stop smoking. Lung cancer screening presents an opportunity to engage high risk smokers in cessation support but our findings suggest such support may need to be available flexibly to be most effective. In collaboration with the ECLS study team
This chapter gives an understanding of evidence about screening at the level needed by a public health practitioner who has to interpret evidence for setting screening policy, or for ensuring high quality service delivery. It takes a very clear and practical approach, illustrating everything with real-life case histories and examples, ranging from infant neuroblastoma to ovarian screening. The issues are simplified into a logical structure. First are the Three Main Biases (healthy screenee effect, length time effect, lead time effect). Then there are the Three Main Evaluation Methods (randomised controlled trials, time trend analyses, case control studies). After that there are the Two Additional Sources of Information (pilot or demonstration projects, modelling), and Test Performance (sensitivity and specificity, positive and negative predictive value, receiver operator characteristic curves). Finally, the chapter describes Summarising Information on all Outcomes (the numbers in the flow diagram, and decision aids).
Twenty years ago, drug discovery was a somewhat plodding and scholastic endeavor; those days are gone. The intellectual challenges are greater than ever but the pace has changed. Although there are greater opportunities for therapeutic targets than ever before, the costs and risks are great and the increasingly competitive environment makes the pace of pharmaceutical drug hunting range from exciting to overwhelming. These changes are catalyzed by major changes to drug discovery processes through application of rapid parallel synthesis of large chemical libraries and high-throughput screening. These techniques result in huge volumes of data for use in decision making. Besides the size and complex nature of biological and chemical data sets and the many sources of data “noise”, the needs of business produce many, often conflicting, decision criteria and constraints such as time, cost, and patent caveats. The drive is still to find potent and selective molecules but, in recent years, key aspects of drug discovery are being shifted to earlier in the process. Discovery scientists are now concerned with building molecules that have good stability but also reasonable properties of absorption into the bloodstream, distribution and binding to tissues, metabolism and excretion, low toxicity, and reasonable cost of production. These requirements result in a high-dimensional decision problem with conflicting criteria and limited resources. An overview of the broad range of issues and activities involved in pharmaceutical screening is given along with references for further reading.
Nanotechnology refers to the interactions of cellular and molecular components and engineered materials—typically, clusters of atoms, molecules, and molecular fragments into incredibly small particles—between 1 and 100 nm. Nanometer-sized particles have novel optical, electronic, and structural properties that are not available either in individual molecules or bulk solids. The concept of nanoscale devices has led to the development of biodegradable self-assembled nanoparticles, which are being engineered for the targeted delivery of anticancer drugs and imaging contrast agents. Nanoconstructs such as these should serve as customizable, targeted drug delivery vehicles capable of ferrying large doses of chemotherapeutic agents or therapeutic genes into malignant cells while sparing healthy cells. Such “smart” multifunctional nanodevices hold out the possibility of radically changing the practice of oncology, allowing easy detection and then followed by effective targeted therapeutics at the earliest stages of the disease. In this article, we briefly discuss the use of bioconjugated nanoparticles for the delivery and targeting of anticancer drugs. [Mol Cancer Ther 2006;5(8):1909–17]
