Introduction

The systematic collection and assessment of family history information is a potentially valuable tool in preventive medicine, and is crucial in the identification of genetic risk.¹ In some situations, family history information alone can form the basis for offering patients appropriately tailored preventive interventions.^{2, 3} In addition, the clinical predictive value of even the most accurate DNA test is strongly influenced by prior probability—such as a positive family history.⁴ Family history is an important risk factor for many of the more common cancers.

Primary care providers (PCPs) have always used family history information as a core tool for their practice.⁵ However, the increasing emphasis on identifying and managing genetic susceptibility, and the question of what might now be considered an “adequate” family history for this purpose, presents real challenges for PCPs.⁶ There is no single agreed upon approach to guide PCPs in taking a genetic family history within office consultations (which are often brief). In practical terms, the systematic collection of family history as it pertains to cancer history is linked with the interpretation of that information which in turn is linked to whether PCPs take appropriate clinical action on the basis of the information collected.

The aim of this review is to provide a partial contribution to the evidence base underlying analytic validity (the ability of a tool to capture accurate family history data) and clinical validity (the ability of a tool to correctly assess or predict disease risk) of tools for capturing and interpreting family history.

Scope and Purposes of the Systematic Review

This systematic review addresses three research questions relating to the clinical utility of ascertaining family history as follows:

1.

What is the evidence that patients or members of the public accurately know and report their family history of each one of, or a combination of, the following cancers: breast, ovarian, prostate, and colorectal?

2.

How well do the different systematic family history collection forms and tools, such as take home tools, web based tools, etc., improve non-systematic approaches to family history collection by PCPs?

a.

Identify tools intended to improve family history collection by PCPs.

b.

Compare these tools against current practice.

3.

What tools exist to enable PCPs to calculate, interpret, and act upon family history based risk information, and how well do these tools perform? For each cancer of interest,

a.

Identify tools designed to facilitate calculation and/or interpretation of family history based risk information, with the purpose of promoting recommended clinical actions.

b.

Assess the evidence for effectiveness of these tools in facilitating calculating and/or interpretation of family history based information.

c.

Assess the evidence for effectiveness of these tools in promoting recommended clinical actions.

d.

For each tool, identify the evidence base for each recommendation.

Methods

Standard systematic review methodology was employed. MEDLINE^®, EMBASE^®, CINAHL^® and Cochrane Central^® from 1990 to July 2007 were searched for primary studies. Eligibility criteria included English-only studies evaluating breast, colorectal, ovarian, or prostate cancers in adults. All primary study designs were included and reviews excluded. For family history tools (FHxTs) and risk assessment tools (RATs) studies were limited to those applicable to primary care settings. Primary care practitioners included family physicians/general practitioners, general internists, obstetricians, gynecologists (obstetrics and gynecology practitioners are PCPs for some women), nurses, nurse practitioners, physician assistants, nutritionists, and behavior counselors. All studies that described or evaluated a tool or standardized method to systematically capture/collect/collate information related to family history for the relevant cancers or history of illness in other family members by any method whether self-report or collected by a professional were eligible. FHxTs were eligible if developed specifically for primary care or developed in other settings but also applicable to primary care. RATs were excluded if they calculated the risk of mutation only or required specialist genetics knowledge.

Results

A total of 15,390 unique citations were identified in the search for all three research questions combined. During two levels of title and abstract screening, 14,840 articles were excluded. A total of 338 citations proceeded to full text screening. From these, a total of 56 studies were eligible for the three research questions.

Question 1: Accuracy of Family History Reporting

A total of 19 unique studies (20 publications) evaluated the accuracy of reporting family history. From these, 16 studies evaluated accuracy by attempting to verify the cancer status of relatives (i.e., accuracy compared with a gold standard), and three evaluated the repeatability or reliability of the informant's knowledge of family history rather than the true status of the relatives (i.e., no external gold standard). For the purposes of this review we use the terms “affected” and “unaffected” to refer to those relatives who have had cancer, and those who have not, respectively.

All but three of the 19 studies recruited participants who had cancer; two studies involved individuals at high risk for colorectal⁷ or breast cancer,⁸ and one involved women undergoing mammography.⁹ There were four case control studies (five publications),^10–14 with controls derived from the general population matched for age,^{10, 11} spouses of the informants or regional general practice lists,¹⁴ and from a linkage with license registration and health care administration database.¹³ In general, family history informant characteristics such as mean age, ethnicity, or education were infrequently evaluated.

Sixteen studies (17 papers)^{7, 8, 10–24} evaluated the accuracy of family history reports by attempting to confirm the true cancer status of the relatives about whom informants provided information. Eight studies ^{13, 14, 19–24} verified the cancer status in relatives reported to be affected and those reported to be unaffected. The other eight studies (nine publications)^{7, 8, 10–12, 15–18} only confirmed the cancer status of relatives reported to be affected. We considered the former studies to be of higher methodological rigor and therefore evaluated these two groups of studies separately.

For the studies verifying affected and unaffected relatives, specificity across all cancers types and with varying modes of collection was consistently high (range 91 to 99 percent), suggesting that patients were very accurate in identifying relatives without cancer. These varied as follows for the different cancers: breast 95 to 98 percent; colorectal 91 to 92 percent; ovarian 96 to 99 percent; prostate 93 to 99 percent. The sensitivity values showed greater variability, with breast cancer having the highest values. The percent varied as follows: breast 85 to 90: colorectal 57 to 90; ovarian 67 to 83; prostate 69 to 79. The extent to which the verification method or the manner of family history collection affected the sensitivity estimates has not been well evaluated.

Fifteen factors were identified within the studies which could influence accuracy of family history reporting. The most frequently reported factors were age (no clear effect), gender (some effect depending on type of cancer and family line), education level (mixed effects) and degree of relatives (consistent trend towards increased accuracy of reporting for first degree compared to second or third).

Question 2: Family History Tools Designed To Improve Collection by Primary Care Professionals

A total of 39 different tools, implemented in 40 unique studies, and reported in 45 publications passed full text criteria. Our initial focus was on identifying studies that described FHxTs developed or used in a primary care setting; however, after careful review, we noted that many studies described tools used in other settings that appeared potentially relevant to primary care (criteria included length, ease of use, complexity of information, need for specialized training). We also sent e-mail queries to all authors of eligible studies that did not provide sufficient detail of the FHxT or a copy of the tool. Fifteen authors (of 16 publications) ^{8, 10, 11, 16, 17, 21, 23, 25–33} did not respond and therefore we were unable to determine whether the FHxT was applicable for use within primary care. For those studies for which we evaluated the FHxT, six tools from seven publications^{13, 18–20, 24, 34, 35} were assessed as inappropriate for primary care; all of these had been developed and used in research settings. Of the remaining 22 publications, four ^36–39 described the prototype and final versions of the same FHxT (RAGS/GRAIDS), which we counted as a single tool; and two ^{40, 41} were companion publications. Thus 18 distinct tools, from 22 publications, were identified as being applicable to primary care settings.

Fourteen tools ^42–55 were designed for completion by patients, and four tools (eight papers) ^{36–41, 56, 57} were designed for use by health professionals. The majority of tools (n = 15) were designed to collect data on family history of breast or breast/ovarian cancer and only two tools captured data on prostate cancer. The published reports indicated that eight of the tools^{46, 48, 49, 51, 52, 54, 55, 57} were used in a proactive way (intended for general or targeted population coming into contact with PCP, irrespective of a known cancer risk or concern), eight (12 papers)^{36, 38–41, 43–45, 47, 53, 56} in a reactive manner (intended for individuals with perceived or recognized familial risk of cancer, including individuals concerned about cancer risk), and two in a mixed approach.^{42, 50} The majority used a paper-based format to collect family history.

The tools were evaluated using a range of study designs. Eleven tools were evaluated relative to “ideal”, best estimate genetic interview, or current (“standard”) practice and seven tools were not evaluated relative to a comparator. Of the five tools evaluated against genetic interview, in three there was no control arm to the study, with interview being completed after FHxT.^{43, 45, 49} Similarly, when compared to current practice, in three studies, patients completed the FHxT followed by capturing information in medical records.^{47, 50, 52} Despite these different study designs the findings were consistent, with FHxTs performing well against “ideal” interviews and significantly better than standard practice.

Question 3: Risk Assessment Tools Designed To Improve Management of Patients

For the purposes of this review we have defined a RAT in primary care as: An active knowledge resource that uses family history data, with or without other relevant evidence to generate case specific advice [knowledge component], designed to support decision making relating to management of cancer risk in individual patients [target decision component, timing component], by health professionals, the patients themselves, or others concerned about them [user component].

Sixteen publications, representing 10 unique studies, were included. All 10 tools were designed to stratify individuals into risk categories, and all had a component which indicated some form of clinical or personal action. Six tools, reported in seven papers,^{43–45, 58–61} were designed to assess risk of breast or breast/ovarian cancer only, four tools (seven papers)^{31, 36–39, 62, 63} were designed to assess risk of breast/ovarian and colorectal cancer, and one tool (two papers) ^{40, 41} focused on breast/ovarian, colorectal and prostate cancer. No tool was identified that focused solely on ovarian, colorectal, or prostate cancer risk.

Of the seven tools intended for use by professionals, five were developed explicitly for use by PCPs, either family physicians (four tools)^{36–39, 58, 60–63} or physicians working in ambulatory care settings (one tool, two papers).^{40, 41} Two appeared to have been developed in settings other than primary care, but intended for eventual use in that setting.^{43, 59} One patient tool³¹ was developed in a primary care setting, and the other two^{44, 45} were considered potentially applicable to use in primary care settings.

Three tools (five publications) were robustly evaluated in controlled trials.^{36, 60–63} The development of one tool was described over four papers from evaluation in “laboratory- type” conditions^{38, 39} to controlled trials in routine practice.^{36, 37} The success of two of these RATs was confirmed by compliance to referral criteria in two studies (three papers), ^{36, 60, 61} however in one study there was no subsequent significant difference in patients identified at increased risk by genetic specialist.³⁶ The final tool (two papers) did not demonstrate any statistical difference in physician confidence and patients' risk perception.^{62, 63}

Discussion and Conclusions

This review explored both the accuracy of family history reporting by patients and the effectiveness of tools for collecting and using familial cancer history in a primary care setting. Ideally, patients are able to report accurate information on their family history, assisted by effective tools, and health care providers are able to use the information to make beneficial preventive and clinical management decisions.

The accuracy of self reported family history has implications for the correct risk assessment and management of patients. Accuracy of cancer family history reporting appears to be dependent on cancer type and method of collection, and accurate reporting of absence of cancer (specificity) appears to be greater than accurate reporting of presence of cancer (sensitivity). Accuracy of recall and reporting may be influenced by both patient factors and by the method used to capture the data (the tool). No studies appear to have examined both of these together, so it is impossible to comment definitively on their relative contributions to any lack of accuracy.

Very few FHxTs have been developed for, and evaluated in, primary care settings. Further, few tools have been compared with either “best practice” (genetic interview) or current primary care practice (family history as recorded in charts). Although the evidence is very limited, and depends on extrapolation of studies of tools in settings other than primary care, it suggests that systematic FHxTs may add significant genetic family history information compared to current primary care practice.

A number of RATs, of varying format and complexity, have been developed for primary care settings, and a few of these have been evaluated in controlled trials. These studies provide tentative evidence for the effectiveness of such tools, but their utility in routine practice has not been established.

Recommendations

1.

Family history is a fundamental element of health information, and the ability to take an adequate and accurate family history should be recognized as a core skill for all PCPs, irrespective of the availability of tools.

2.

Consensus should be reached on the extent of family history enquiry necessary for different clinical purposes and circumstances, taking into account the likelihood of accuracy of self reported information for different relatives, and the use to which the information will be put (e.g., overall or specific risk assessment). Until the evidence base is clear, it is suggested that a minimum adequate cancer family history should include information on siblings, parents and grandparents (and the paternal and maternal lineage of the latter), specific enquiry about whether other relatives had the cancers of interest, and the ethnicity of the respondent. When cancer is identified, the age of diagnosis should also be noted, and other relatives with similar or related conditions identified.

3.

The benefits, costs and harms of using patient-completed tools for systematic family history collection and risk assessment, as a substitute for, or complement to, professional tools should be further examined. As well as assessing technical outcomes such as accuracy and completeness of data captured, evaluations should consider outcomes which relate to patient “empowerment” and the use of practitioner and health care resources.

4.

Further research is required to identify the specific strategies and tool features which promote the most accurate reporting of family history information.

5.

The optimum interval for updating a patient's family history information in primary care should be formally evaluated.

6.

Further evaluation of FHxTs and RATs in routine clinical settings and practice is required. Studies should: adopt appropriate comparators (generally current practice); ensure that tools are optimized (in terms of, for example, face and content validity) before evaluation; measure outcomes that relate to utility in routine practice; measure outcomes that provide information on potential costs or harms as well as benefits; and address or explore contextual factors which may modify utility in practice (e.g., practice infrastructure, time available).