2c Diagnosis and Screening

Question 1

What is screening?

Answer 1

Screening is the process of identifying healthy people who may be at increased risk of disease or condition. The screening provider then offers information, further tests and treatment. This is to reduce associated risks or complications

Or

Screening refers to the use of simple tests across an apparently healthy population in order to identify individuals who have risk factors or early stages of disease, but do not yet have symptoms

Question 2

What criteria can be used to assess whether a condition potentially warrants screening efforts?

Answer 2

Wilson and Jungner classic screening criteria, WHO 1968

The condition sought should be an important health problem.
There should be an accepted treatment for patients with recognised disease.
Facilities for diagnosis and treatment should be available.
There should be a recognisable latent or early symptomatic stage.
There should be a suitable test or examination.
The test should be acceptable to the population.
The natural history of the condition, including development from latent to declared disease, should be adequately understood.
There should be an agreed policy on whom to treat as patients.
The cost of case-finding (including diagnosis and treatment of patients diagnosed) should be economically balanced in relation to possible expenditure on medical care as a whole.
Case-finding should be a continuing process and not a ‘once and for all’ project.

Question 3

What are the key questions to ask when deciding on whether to screen for a health problem?

Answer 3

The disease
Is it an important health problem?
Is the natural history well understood?
Is there a long time between the presence of risk factors/sub-clinical disease to overt disease?
Does early intervention improve clinical/public health outcome?

Screening test
Is the test valid (sensitivity and specificity)?
Is the test simple, reliable and affordable?
Is the test acceptable to patient and staff?

Diagnosis and treatment
Is access to diagnostic facilities available and rapid?
Is treatment effective and accessible?
Is it cost-effective?
Is it sustainable?
Does benefit outweigh the harm?

Question 4

What are the limitations of screening?

Answer 4

Screening cannot offer a guarantee of protection
False positive results
False negative results

Question 5

What newborn screening programmes are run in the UK?

Answer 5

Question 6

What antenatal screening programmes are run in the UK?

Answer 6

Question 7

What adult screening programmes are run in the UK?

Answer 7

Question 8

What is the difference between screening, diagnostic tests and case finding?

Answer 8

The primary purpose of screening tests is to detect early disease or risk factors for disease in large numbers of apparently healthy individuals.

The purpose of a diagnostic test is to establish the presence (or absence) of disease as a basis for treatment decisions in symptomatic or screen positive individuals (confirmatory test).

The purpose of case finding is to target resources at individuals or groups who are suspected to be at risk for a particular disease. It involves actively searching systematically for at-risk people, rather than waiting for them to present with symptoms or signs of active disease.

Question 9

What are the differences between diagnostic tests and screening?

Answer 9

Question 10

Give an example of the uses of case finding.

Answer 10

Communicable disease control
Case finding is a key strategy in communicable disease outbreak management (e.g. sexual partner ascertainment in syphilis outbreaks; household/work contacts in food-borne outbreaks). The purpose is to identify at-risk individuals and offer them screening and treatment if necessary.

Health systems data
Can be used to identify ‘missed’ risk groups (e.g. registered GP patients over 50 years of age with a BMI>30 who may not be on the register of people at risk for coronary heart disease). Using population-based data such as the Index of Multiple Deprivation to target interventions at disadvantaged populations.
The King’s Fund software for ‘patients at risk of re- hospitalisation’ (PARR) use patterns in routinely collected data to forecast which individuals are at higher risk of emergency hospital admission in the forthcoming year (www.kingsfund.org.uk/parr).

Question 11

What are receiver operating characteristic (ROC) curves and how can they be used in medicine?

Answer 11

The ROC curve is a graph with false positives (sensitivity) on the Y-axis and true positives (1-specificity) on the X for every possible cut-off of a test.

It is effectively a graphical version of every possible 2x2 table that a screening programme (or diagnostic test) could produce for every possible cut-off criteria for a positive test. E.g. By increasing or decreasing the level required to be diagnosed.

Any point directly in the middle of a ROC curve (X=Y), means that the test will classify the same number of false positives as it will false negatives. In the example, below it would diagnose the same number of people as being obese but aren’t (false positives), as it would not diagnose truly obese people (false negative).

Points to the left of this equal line (x=y), have a higher proportion of correctly diagnosed patients (true positive) than false positives and thus are deemed better cut-offs.

The two main uses of ROC curves are:
To set a cut-off value for a test result (for continuous diagnostic variables)
To compare the performance of different tests measuring the same outcome (test validation)

This is a good video - youtube.com/watch?v=4jRBRDbJemM

Question 12

What is the optimal test threshold according to this ROC curve?

Answer 12

Question 13

How can you use a ROC curve to decide on the best threshold or cut-off for a diagnostic test?

Answer 13

The perfect test is one that sits on the top left of an ROC curve (where X=0 and y=1).

After this, you need to decide on how many false positives you are willing to allow in your test in order to increase the sensitivity, this will be dependent on the specific disease being tested for.

Question 14

How can you use an ORC curve to compare diagnostic or screening tests?

Answer 14

The larger the area under an ROC curve, the better the test.

Question 15

What are the ethical considerations of screening programmes?

Answer 15

Beneficence
Screening programmes may have large benefits at population level for those who can be offered early treatment but not every case will benefit

Non-malfeasance
Psychological harm from false positives
Preventable death resulting from false-negative tests
Iatrogenic harm from the subsequent diagnostic test
Unwarranted reassurance from false-negatives

Justice
Screening programmes should be used only when all other primary preventive measures are in place
Ensuring equality in uptake and linkage into care pathways among deprived and affluent populations can be tricky

Autonomy
Communicating risk to patients is difficult
It is questionable whether people who partake in a screening programme truly understand the consequences

Question 16

What are the economic considerations of screening programmes?

Answer 16

Introducing and running a screening programme is expensive and associated with large numbers of people to be screened (including administrative costs) to find a small number of cases.

The opportunity cost of the screening programme (including testing, diagnosis and treatment, administration, training and quality assurance) should be economically balanced in relation to expenditure on medical care as a whole.

Economic evaluations should be subject to sensitivity analysis and discounting.

Question 17

What are the legal considerations of screening programmes?

Answer 17

Test license and safety
The employed screening test needs to be licensed and safety approved by a statutory body

Qualification and Accreditation
To assure standards, diagnosticians involved in processing the test must be qualified, registered and accredited by a statutory body. To retain their accreditation, they must deal with a minimum number of abnormal cases each year

Confidentiality
Individual-level information collected through screening must be kept confidential to authorized personnel only and managed in accordance with Caldecott Guidelines

The right NOT to be screened
For certain diagnoses (e.g. genetic screening for Huntington’s disease), the right of children not to be screened may be protected in law. Likewise, the law offers protection to prisoners and to people with learning difficulties against coercion into screening programmes. The should be no discrimination of non-participants

Consent
Documentation of consent to be screened may be necessary in writing (see informed choice)

Question 18

What are the social considerations of screening programmes and which increase or decrease ?

Answer 18

Health beliefs and attitudes are important influences in participation in screening, but may vary significantly between target population subgroups. These need be considered in the planning and monitoring stage in order to ensure that any new screening programme does not exacerbate health inequalities, e.g. between social classes or between different ethnic groups.

Factors that may increase participation in screening
Knowledge of condition
Perception of susceptibility
Perception of disease severity
Knowledge of availability of treatment

Factors that may decrease participation in screening
Disease phobia
Stigma associated with condition
Unpleasant diagnostic tests and treatment
Socio-economic factors (e.g. income, education, deprivation, employment)
Socio-demographic factors (age, sex, ethnicity, language, creed)
Accessibility of screening sites

Question 19

What is required to have an informed choice in relation to screening?

Answer 19

The GMC proposes that people need the following information in order to make such an informed decision (or choice) in screening:

The purpose of the screening;
The likelihood of positive/negative findings and possibility of false positive/negative results;
The uncertainties and risks attached to the screening process;
Any significant medical, social, or financial implications of screening for the particular condition or predisposition;
Follow up plans, including availability of counselling and support services.

Question 20

What are the general problems with screening?

Answer 20

Evidence that a screening programme will reduce mortality is not sufficient alone to introduce a screening programme. A full analysis of benefits and harms should include not only the screening, but also the follow-up tests and indicated treatments.

Many screening programmes focus on maximising participation. However, a high participation rate is not needed to achieve screening population-level benefit and cost-effectiveness. Maximising participation per se may not achieve equitable access. It is known that there are groups in the population where participation is lower, including more deprived communities, ethnic minority communities, Gypsy and traveler groups.

Incentive payments to service providers (usually for the participation rate) may reduce the motivation to provide real informed choice.

Increasing informed choice should lead to a better benefit:harm ratio.

Informed choice should be a dimension of screening programme evaluation.

Assessment should include availability of understandable information, presenting risk data as absolute risk, and access to choice and decision support.

Question 21

What are the two main approaches to screening programmes?

Answer 21

Opportunistic - screening is done as part of routine care when patients visit their doctors

Proactive - the population targeted for screening are actively identified and invited to participate in the screening programme.

Question 22

What costs should be considered when setting up a screening programme?

Answer 22

The cost of the test itself
Costs of reading and interpreting the test
Cost of diagnostic follow-up tests
Cost of the programme management and data processing
Cost of treating more cases that are identified due to the screening programme
Cost of treating more advanced disease in the absence of a screening programme
Opportunity costs for the health service and the individual.

Question 23

What is the UK National Screening Committee?

Answer 23

In the UK, the National Screening Committee (UK NSC) advises ministers and the NHS in the four UK countries about all aspects of screening and supports the implementation of screening programmes. Conditions are reviewed against specific evidence review criteria according to the UK NSC evidence review process in order to establish the screening programme’s viability, effectiveness and appropriateness. The UK NSC does this by:

Reviewing evidence about the effectiveness of screening
Commissioning research on screening
Advising on the introduction of new screening programmes
Reviewing the continued delivery of screening programmes
Assessing the quality of screening programme delivery.

Question 24

What is quality assurance in screening programmes?

Answer 24

Screening programmes must participate in external Quality Assurance and have internal quality assurance processes that ensure failsafe is integral to the programme and incident management occurs in line with failsafe document/map of medicine and national guidelines for incident management

Question 25

What are the steps in setting up a screening programme?

Answer 25

1. Identification of target population
2. Invite target population
3. Inform target population of screening programme and gain consent
4. Administer screening test
5. Interpret result of the test
6. Communicate results of the test
7. Follow-up testing/surveillance (as required)
8. Treatment (as required)
9. Data management systems
10. Programme coordination, oversight, and quality assurance
11. Ongoing monitoring and evaluation

Question 26

How can screening programmes be evaluated?

Answer 26

Evaluating screening programmes

The UK NSC proposes 20 criteria for appraising the viability, effectiveness and appropriateness of a screening programme. These draw on the Wilson and Jungner criteria and can be summarised as:

The condition
Is there good evidence (from systematic reviews or randomised controlled trials) showing that early intervention in the disease improves outcomes?

The test
Is it safe?
Will it work in our population and healthcare system?

The intervention/treatment
Is there an effective treatment that can be used following early identification of the disease?

The programme
What are the benefits and harms of the screening programme?
Is it cost effective?

Implementation criteria
Are there appropriate facilities, staffing, expertise, training for treating the condition?
Is there an agreed plan for managing and monitoring the quality of the screening programme?

Question 27

What is Lead Time Bias?

Answer 27

When screening appears to increase survival time simply because the disease is detected earlier. Once this is taken into account, there may be little or no effectiveness of the screening test (i.e. improvement in survival time).

Question 28

What is Length Time Bias?

Answer 28

An overestimation of survival because long-duration cases are more likely to be detected and treated than short-duration cases. For example, annual PSA screening is more likely to detect a slow-growing tumour of the prostate, which is also more likely to be detected while still at a treatable stage.

Question 29

In what situations does the UK NSC review evidence for screening?

Answer 29

A regular review when the current recommendation is not to offer population screening is due
A regular review when the current recommendation is to offer population screening
When new evidence is published which brings into question a current recommendation on screening
When a proposal is made to modify, or make big changes to, a current screening programme
When a proposal for a new topic which has not been previously reviewed by the UK NSC is submitted.

Question 30

Which screening tests are not reccomended as they are deemed to be too harmful?

Answer 30

Question 31

What is genetic screening?

Answer 31

Genetic screening involves testing members of a population (or sub-population) for a defect or condition, usually where there is no prior evidence of its presence in individuals or their relatives, and as part of a public health service.

Alternatively, the offer of screening may be limited to a sub-population that is at particular risk of a genetic condition.

Genetic screening is distinct from screening for other conditions in that it has the potential impact not just on the individuals being screened, but also their family members and society generally

Question 32

How is consent for genetic screening different than regular screening?

Answer 32

Patients need to be sufficiently informed about the implications of genetic screening before they can provide informed consent.

The public view genetics with a sense of inevitability. However, a genetic condition alone may be insufficient to cause disease, but may modify risks from environmental or lifestyle factors.

The voluntary nature of the screening process must be emphasised

Question 33

Why might counselling be given during genetic screening?

Answer 33

To reduce potential psychological distress, counselling should be available to provide information about genetic risk and explain choices regarding genetic testing and further management.

Support is needed for individuals who must consider issues such as stigma, disclosure to family members, and confidentiality.

Couples known to carry a recessive or dominant single gene defect or sex-linked condition need counselling about their reproductive options. This may include prenatal diagnosis and possible pregnancy termination in the case of an affected fetus, and preimplantation genetic diagnosis (PGD). In vitro fertilisation (IVF) in combination with PGD may provide such high-risk couples with a pregnancy with no chance of genetic disorder transmission.

Question 34

What stigmas can be associated with genetic testing?

Answer 34

The public’s understanding of genetics may be limited and can lead to stigma.

Misunderstanding of the genetic risk of developing diseases can increase stigmatisation. This may be around life expectancy, lifestyle choices, or decisions about having children.

Identification of a genetic condition before birth raises issues of whether the parents wish to terminate the pregnancy. Some commentators have argued that the ability to only select ‘perfect’ babies is a form of eugenics.

Question 35

What are the difficulties with confidentiality and genetic screening?

Answer 35

Like other medical information, results from genetic testing are considered confidential. Under normal practice, the doctor patient relationship protects against disclosure of genetic information. However, there is less clarity in cases where relatives wish to know the results of a family member’s genetic test, as it may have direct relevance for them.

Another particular dilemma is the case of a pregnant woman wanting to know the result of a test taken by the baby’s father.

In the UK, the Human Genetics Committee, General Medical Council and the Department of Health endorse disclosure only when the benefits substantially outweigh the patient’s claims to confidentiality.

The storage of genetic screening data and registries of patients creates particular concern, given that the results may impact negatively on family members.

It is unclear if doctors are ethically permitted to inform relatives in cases when the result of a genetic test indicates real risk to their health.

Doctors may also be faced with a decision about whether to persuade patients about the need to disclose their test result to relatives.

Although most professional bodies believe that disclosure should not be against patients’ consent, there have been some cases where the rights of relatives have won priority.