Symptom records, pain diaries and patient-reported outcomes: what research says

Symptom records come in several forms: a daily diary of pain, a chart of how heavy each day of bleeding was, a single 0 to 10 pain rating, and long questionnaires about how a condition affects life. This article describes what research has found about each of them in endometriosis, adenomyosis and chronic pelvic pain. Much of the work was done in endometriosis, and much of it was designed for clinical trials ^[3][12]. Studies describe how these tools were built, how consistently they measure what they claim to measure, how much change on them has been judged meaningful, and where they fall short, including recall error, the work of completing them, and weak links between scores and what is seen at surgery or on imaging. The article describes research. It does not advise anyone what to record or do.

What a patient-reported outcome measure is

Clinicians measure many things directly, such as a blood pressure or a hemoglobin level. Pain, fatigue, mood and how heavy a period felt cannot be measured this way. They are known only through the person who has them. A patient-reported outcome measure is a standardized way of asking about such experiences so that answers can be compared across days, people and studies. The category covers a single-question pain rating, a seven-day diary, a pictorial chart, and a multi-scale quality-of-life questionnaire.

In endometriosis, the developers of one diary system noted that, without established sensitive and specific biomarkers, disease severity in clinical studies is determined by patient-reported symptoms and impacts ^[3]. That statement reflects the way trials of endometriosis treatments are designed. It is a statement about research practice, not a claim that symptoms and disease extent are the same thing, a point returned to below.

A useful way to organize the field is by what is being asked and when. Some tools ask about intensity at one moment. Some ask for a daily entry that is later summed over a menstrual cycle. Some ask about impact on work, relationships and emotions rather than about the symptom itself. Each design answers a different question, and each has different strengths and failure modes.

Single-item pain scales: VAS, NRS and verbal ratings

The simplest tools ask for one number. A VAS is typically a 100 mm line, with the person marking a point between the two ends ^[18][30]. An NRS asks for a whole number, most often from 0 to 10. A verbal rating scale asks for a category such as none, mild, moderate or severe.

A systematic review compared these formats in adults across many conditions. It included 54 of 239 screened papers. Eight versions of the NRS were found, from 6-point to 101-point, and 24 different descriptors were used to anchor the ends. In the 19 studies that reported compliance, the NRS had better compliance than the VAS or verbal scales in 15, and 11 studies recommended the NRS on grounds of compliance, responsiveness and ease of use, while 29 gave no preference. NRS and VAS scores generally corresponded, with a few exceptions of systematically higher VAS scores. The authors noted that the variation in anchors and response options had not been tested for its effect on scores ^[14]. This review did not focus on pelvic pain. Postoperative pain intensity was the most frequently studied setting, and six studies were in cancer.

For endometriosis specifically, a systematic review searched MEDLINE and EMBASE from 1980 to December 2012 for endometriosis treatment studies that named a pain scale. Of 736 publications identified, 258 met inclusion criteria. The VAS was the most frequently used scale. The VAS and NRS showed a good balance of strengths and weaknesses compared with older scales such as the Biberoglu and Behrman scale. For minimal clinically important difference (MCID), only the VAS, NRS and Brief Pain Inventory had reported values, and among these only the VAS had been studied in people with endometriosis, with an estimate of 10 mm. The authors proposed using a VAS or NRS separately for dysmenorrhea, deep dyspareunia and non-menstrual chronic pelvic pain, combined with a global impression rating and a quality-of-life scale ^[4]. That recommendation is the review authors' interpretation. The review itself is limited to English, French and Portuguese publications and to studies that reported a treatment.

The 10 mm figure came from analyses of two placebo-controlled trials with 281 participants who had laparoscopically confirmed endometriosis and moderate-to-severe endometriosis-associated pelvic pain. Participants recorded pain on a VAS at baseline and at the end of treatment, and also rated their satisfaction on a modified Clinical Global Impression scale. The anchor-based MCID was 7.8 mm and the distribution-based MCID was 8.6 mm, supporting a 10 mm margin for comparing treatments ^[18]. A separate small prospective study of 37 women with endometriosis and baseline pain above 50 mm on a VAS, who had received a procedure called pertubation with lignocaine, derived a much larger minimal important difference of 39 mm or 49% for the group that felt "somewhat better" ^[19]. The two studies used different populations, different anchors and different treatments. The gap between 10 mm and 39 mm illustrates that a threshold for "meaningful" change depends on the method used to define it, the starting level of pain and the setting.

A consensus group of chronic pain researchers has also recommended pain intensity on a 0 to 10 NRS as a core outcome measure for chronic pain trials, and has advised that two or more different methods be used to judge the clinical importance of a change ^[20]. The same group listed six core domains for chronic pain trials: pain, physical functioning, emotional functioning, participant ratings of improvement and satisfaction, symptoms and adverse events, and participant disposition ^[21]. These recommendations came from a consensus meeting of specialists from academia, government agencies and industry, and describe how trials are best designed, not how an individual should keep records.

Quality-of-life questionnaires: the Endometriosis Health Profile

Pain intensity does not describe what a condition does to daily life. The Endometriosis Health Profile-30 was developed in three stages. In the first, 25 women were interviewed to generate items. In the second, an 87-item questionnaire was mailed to identify the most important dimensions. In the third, reliability and validity were evaluated. The final instrument has a core questionnaire of 30 items in five scales (pain, control and powerlessness, emotional well-being, social support and self-image), plus six optional modules of 23 questions on sexual intercourse, work, relationship with children, feelings about the medical profession, treatment and infertility. Internal consistency was high for all scales (Cronbach's alpha 0.83 to 0.93 for the core questionnaire), test-retest correlations were 0.88 to 0.98, and the scales correlated with the corresponding scales of the generic Short Form-36 (-0.41 to -0.73) ^[1]. Because items were drawn from patient interviews rather than from existing clinical scales, the authors described content validity as established through the patient-generated approach ^[1].

A short form, the EHP-5, uses 11 items: five from the core questionnaire and six from the modules. It was developed through three studies, and the developers described it as useful where a short and economical measure is wanted ^[2].

A systematic review of how the EHP has been used covered 139 papers published after 2001. It found the tools deployed most often in medical treatment studies (35) and surgical studies (21), with 32 psychometric or cross-cultural validation studies. Studies were mainly from Europe and North America. Most women reported improved health-related quality of life after treatment, regardless of the intervention. The review reported that scores worsened when medication was stopped in some studies, and that younger participants reported a more negative impact. Studies based on anchors found the largest mean changes in the "control and powerlessness" domain, followed by "pain". The authors did not run a meta-analysis because the interventions and papers were too varied ^[5]. Because the review did not pool results, the size of any change cannot be summarized from it.

Validation work has produced mixed results by country and language. A confirmatory factor analysis of the Danish EHP-30 in 304 women with endometriosis, recruited from three referral clinics and a patient association, supported the original five-factor structure, with a response rate of 87.6%. Diagnosis was confirmed in medical records for 84.2% and by histology for 66.8%. Menstrual cycle phase and medication use at the time of completion were not recorded ^[6]. In contrast, a Norwegian study of 157 women recruited from a patient association found that factor analysis supported a three-factor model for the core questionnaire and could not support construct validity for the self-image and treatment scales. Floor effects, meaning many people scoring at the lowest possible value, were seen in several scales (self-image 20.1%, work life 33.9%, relationship with children 34.2%, medical profession 20.5%). The authors concluded that the self-image construct was not measured appropriately in the Norwegian version ^[7]. Both studies recruited volunteers who may differ from the wider population with endometriosis.

In a post hoc analysis of two trials in 871 and 815 women with moderate-to-severe endometriosis-associated pain (Phase III, double-blind, placebo-controlled), EHP-30 domains improved over three and six months, with large effect sizes. Thresholds of meaningful change were estimated at 20 to 35 points, using patient global impression, distribution-based methods and daily diary indicators ^[22]. As with the pain scale thresholds above, these figures come from trial participants who had moderate-to-severe pain and may not transfer to everyone with the condition.

Daily diaries built for trials

A group of newer instruments were designed specifically as daily electronic diaries to serve as endpoints in clinical trials. Their development followed the 2009 FDA guidance on patient-reported outcomes and used patient interviews and cognitive testing before any measurement testing ^[3][23].

The Endometriosis Pain and Bleeding Diary (EPBD) was developed from clinician input, five focus groups with 38 participants and three rounds of cognitive interviews with 22 participants. Participants described two distinct types of pain, intermittent and continuous, and said that pain and bleeding or spotting with intercourse were important to monitor. A 17-item version was tested at four United States sites in a non-intervention study. Pain items correlated with a modified Brief Pain Inventory short form (0.46 to 0.61), and women with severe symptoms scored higher than women with mild symptoms. The developers noted that further studies were needed to confirm dimensionality and scoring and to assess responsiveness ^[23].

The Endometriosis Pain Daily Diary (EPDD) was built on the EPBD, a literature review, clinician interviews and patient interviews in the United States and Japan. Its third version has 11 items: five core items on dysmenorrhea, non-menstrual pelvic pain and dyspareunia, and six extension items on sexual activity, daily activities and rescue medication use. Translatability was assessed across 17 languages, and the developers reported feedback from United States and European regulators ^[24]. The Endometriosis Symptom Diary (ESD) and Endometriosis Impact Scale (EIS) were developed with concept elicitation interviews of 45 women with surgically confirmed endometriosis in the United States, Germany and France, and cognitive interviews of 31. Pelvic pain was the most frequent, severe and bothersome symptom, and was reported as greatest during menstruation and during or after intercourse. The measurement properties of these two measures were described as still to be established at the time of that paper ^[3]. A further instrument, the Endometriosis Daily Diary, was modified from a diary originally made for dysmenorrhea. In 30 concept elicitation interviews, 30 cognitive debriefing interviews and a 15-person pilot, all with United States women, content validity was judged good and psychometric validation was named as the next step ^[25]. Separately, daily items on dysmenorrhea and non-menstrual pelvic pain impact were developed through qualitative research and tested in a phase II trial, where they showed evidence of reliability, convergent validity and responsiveness ^[26].

Two features of this work stand out. First, the content came from patients, and descriptions of pain and its impacts were largely consistent between United States and European participants, with differences mostly in the words used for pain location, such as pelvis versus abdomen ^[3]. Second, many of these tools have been validated for content (do the questions make sense and cover what matters) more fully than for measurement properties such as responsiveness. Content validity and measurement properties are assessed separately in the standards used to evaluate questionnaires ^[11].

A qualitative study of 25 patients in Germany and the United States and four expert clinicians asked how daily scores should be summarized. Patients and clinicians ranked "worst pelvic pain" as the most meaningful pain concept. Patients with daily pain preferred a score summarizing all 28 days of a cycle, while patients whose pain came on selected days, and their treating clinicians, preferred scores based on the most severe days. For the 0 to 10 "worst pelvic pain" NRS, a 2- or 3-point reduction was considered meaningful by most participants, depending on baseline severity ^[27]. The sample was small and the study did not test any treatment.

Bleeding charts and the pictorial blood loss assessment chart

Heavy menstrual bleeding is a commonly reported outcome in adenomyosis research ^[13][33], and one study described below found higher chart scores in people with endometriosis ^[30]. The pictorial blood loss assessment chart (PBAC) asks the person to record, for each pad or tampon, how soiled it was, using a set of drawings, and to record clots and flooding. The scores are summed per cycle. The original work compared chart scores with blood loss measured by the alkaline hematin laboratory method in 28 women over 55 cycles. A score of 100 or more, used as a test for menorrhagia, had specificity and sensitivity above 80% ^[28]. This study was small and used pads and tampons available at the time.

Later work was less consistent. A prospective study of 103 consecutive women who complained of heavy periods found poor correlation between PBAC scores and measured blood loss and could not validate the earlier finding ^[29]. A systematic review of pictorial methods identified nine studies that validated PBAC scoring systems against the alkaline hematin technique. Sensitivity ranged from 58% to 97%, specificity from 7.5% to 95.5%, and the cut-off score above which heavy bleeding was diagnosed ranged from 50 to 185. Several modified charts had no objective validation, and chart design, scoring and cut-offs were widely inconsistent. The reviewers concluded that PBACs suit controlled clinical studies where outcomes are defined, and that the lack of standardization precluded widespread use in primary care ^[8]. A broader systematic review of 71 studies of methods for measuring menstrual blood loss concluded that every method has limitations, that pictorial methods had been more comprehensively validated than questionnaires and models, and that pictorial methods strike a balance between ease of use and validated accuracy ^[9].

In endometriosis research, a study of 315 women undergoing laparoscopy for various reasons asked them to complete the Higham PBAC and to grade dysmenorrhea on a 100 mm VAS and a verbal scale. Of 163 women with endometriosis and 152 without, the median PBAC score was 110 in women with endometriosis and 84 in those without, and 53% versus 37% scored 100 or more. Dysmenorrhea scores were also higher in the endometriosis group ^[30]. The comparison group included women with normal pelvises, ovarian cysts and pelvic inflammatory disease, so it was not a healthy control group. The study shows a group difference, not a way to tell individuals apart.

Adolescents are a separate case. A systematic review of 57 studies identified 19 instruments for dysmenorrhea and heavy menstrual bleeding in people aged 10 to 19. The PBAC was the most frequently used instrument in adolescents, yet the clinical relevance of its adult cut-off had not been established for this age group, and one modified adolescent version had low sensitivity and specificity. The review judged two other instruments, the Period ImPact and Pain Assessment and the Adolescent Menstrual Bleeding Questionnaire, to be the ones validated and feasible in this group ^[31].

Questionnaires and outcome sets in chronic pelvic pain and adenomyosis

For women with chronic pelvic pain without an identified cause, a systematic review of 24 randomized trials found 136 reported outcomes and outcome measures. Pelvic pain was reported in all trials, but only half reported quality of life, clinical effectiveness and adverse events. The review proposed interim use of commonly reported outcomes while a core outcome set was developed ^[10]. A companion review of 19 quality-of-life instruments used in chronic pelvic pain applied standard criteria for judging how instruments are developed. It found that development was inadequate for all 19, with no high-quality evidence for relevance, comprehensiveness or comprehensibility. Thirteen of the 19 were generic rather than specific to pelvic pain, half did not involve patients in their development, and cognitive interviews were done for only about one in five ^[11].

A review of 191 nonsurgical trials of chronic pain associated with endometriosis (1,286 records screened) found pain assessed in 98.4% of studies, physical functioning in 29.8% and emotional functioning in 6.8%. Few trials combined more than two domains, so the biopsychosocial aspects of pain were not comprehensively captured. The measures themselves varied widely ^[12]. In an international consensus process with 116 health professionals, 31 researchers and 206 patient representatives, the core outcomes for endometriosis trials evaluating pain and other symptoms were overall pain, improvement in the most troublesome symptom, and quality of life ^[32]. These are recommendations for what research should report, not instruments in themselves.

In adenomyosis, a systematic review of 38 studies (5,175 participants) found 203 outcomes assessed with 133 different measures. Dysmenorrhea was reported in 82%, heavy menstrual bleeding in 79% and uterine volume in 71%, with 14 different measures for dysmenorrhea and 17 for heavy bleeding. Quality of life was reported in 24% of studies and patient satisfaction in one ^[13]. An international consensus study with 150 health professionals, 17 researchers and 334 people with lived experience of adenomyosis, from 48 countries, produced a core outcome set of 24 specific and 26 generic outcomes across nine domains, including pain and uterine bleeding. Only 58% of participants returned for round two, and people from outside Europe were under-represented. The authors noted a lack of scientific evidence about which symptoms are caused by adenomyosis and which by coexisting conditions such as endometriosis ^[33]. This suggests that symptom records in adenomyosis research may reflect more than one condition ^[33].

A review of dysmenorrhea measures found 19 patient-reported tools evaluated in 30 studies. Most tools had inadequate development quality, and only one, the Dysmenorrhea Symptom Interference scale, had enough evidence to be considered for recommendation ^[34].

Instruments that target pelvic pain have also been tested in smaller studies. The ENDOPAIN-4D was evaluated in 199 women with proven endometriosis at baseline and 12 months after medical or surgical treatment. It has four dimensions (pain-related disability, painful bowel symptoms, dyspareunia and painful urinary symptoms), and the minimal clinically important difference of the global score was estimated at 10.9 on a 0 to 94 scale ^[35]. The Pelvic Pain Impact Questionnaire was tested in a Hungarian cross-cultural study of 240 women with chronic pelvic pain or endometriosis, with high reliability (Cronbach's alpha 0.881, intraclass correlation 0.977) and correlations of 0.24 to 0.71 with other measures ^[36]. Neither has been compared head to head with the others in the studies described here.

Pain, thinking and mood: the biopsychosocial layer

Pain intensity is one of several domains that consensus groups list for chronic pain, alongside physical and emotional functioning ^[21]. Research on endometriosis has also examined psychological and sensitization-related dimensions with self-report questionnaires.

In a cross-sectional analysis of 236 women at a tertiary referral center for endometriosis and pelvic pain, higher scores on the Pain Catastrophizing Scale were independently associated with worse pain-related quality of life on the EHP-30 pain subscale, after accounting for pain severity, dysmenorrhea severity, abdominal wall pain and other factors ^[37]. In a prospective cohort of 239 patients (71% followed up, mean 16.1 months) at a tertiary center in British Columbia, higher baseline scores on the Central Sensitization Inventory, a 25-question self-report scale, were associated with more chronic pelvic pain, deep dyspareunia, dyschezia and back pain at follow-up after surgery, when baseline pain was held constant ^[38]. Both studies are observational and come from specialty centers. They show associations among questionnaire scores, and do not show that either scale identifies a cause of anyone's pain.

These findings sit alongside consensus recommendations to assess more than pain intensity ^[21][32]. They also show that questionnaires about thinking, mood and sensitization are in use in research, which means that a "symptom record" in a study can include much more than a pain rating.

How well people remember: recall, compliance and real-time sampling

Diaries are used partly because remembering is imperfect. A prospective study of 97 rheumatology patients, who made five or six momentary pain ratings per day plus a daily recall rating for 28 days, found that peak and end momentary ratings predicted recall of average pain beyond the actual average. The effect was small, and varied between individuals ^[15].

In endometriosis, a study within a large e-cohort asked 1,752 participants to rate their worst intensity of dysmenorrhea, dyspareunia, dyschezia, dysuria and abdominal pain across five life periods, then repeated the questions about one year later. Agreement was moderate to good: intraclass correlation 0.74 for dysmenorrhea, 0.72 for dyspareunia, 0.68 for dysuria, 0.62 for dyschezia and 0.58 for abdominal pain ^[16]. Reliability across two retrospective reports is not the same as accuracy against a record made at the time, and the study did not have such a record.

Compliance with diaries is its own problem. In a study of chronic pain patients (not endometriosis) who were asked to make three entries per day for 21 days, participants handed in paper diary cards matching 90% of the assigned times, but electronic time stamps from an instrumented binder indicated that actual compliance was 11%. Compliance with an electronic diary that had compliance-enhancing features was 94% ^[39]. A systematic review of 62 publications on electronic pain diaries, mostly in female chronic pain patients, found compliance was generally high and was associated with shorter diaries, older age, having a user manual, financial compensation and alarms ^[40]. Both findings come from research settings where participants were enrolled and, in some cases, compensated.

A smartphone study of an experience sampling method in 28 people with endometriosis prompted ratings ten times a day for one week at random moments. Compliance with these prompts was 52%. End-of-week pain scores were higher than the average of the momentary scores and showed peak reporting. The momentary scores had strong concurrent validity against several established questionnaires ^[41]. The sample was small, the follow-up short, and the burden of ten prompts a day is high. A review of digital symptom-tracking technologies in endometriosis noted that many tools from related chronic pain conditions had not been specifically evaluated in people with endometriosis-associated pain ^[42].

Burden: what it takes to complete these tools

Most validation studies report psychometric properties and say little about what completion costs the person. Information in the sources above is indirect. The EPBD has 17 items ^[23]. The EPDD went from a 43-item version tested in cognitive interviews to an 11-item version ^[24]. The review of electronic diaries found compliance was higher with shorter diaries ^[40]. The experience sampling study found that only about half of prompts were answered when they arrived ten times a day ^[41]. The EHP-30 has a 30-item core and up to 23 module items ^[1], and the EHP-5 was developed because a short and economical instrument was wanted for clinical settings ^[2].

Records also carry costs of other kinds. Endometriosis affects work and quality of life. A multicenter study across ten countries (1,418 women) found an average of 10.8 lost work hours per week for affected women, mostly from reduced effectiveness while working ^[43]. That study did not measure diary burden, and it is cited only to show that people who might be asked to complete detailed records are often managing a heavy load already. None of the sources reviewed for this article directly measured distress or time spent completing endometriosis symptom diaries. A Cochrane review of feedback from PROMs in clinical practice noted that no included study had reported on distress following or related to completing PROMs ^[44].

Using records in research and in clinical visits

In research, patient-reported measures define the primary endpoints of most endometriosis pain trials, which is why the work on content validity, thresholds and standardization described above exists. Harmonization projects have also standardized the baseline questionnaire. The World Endometriosis Research Foundation's Endometriosis Phenome and Biobanking Harmonization Project produced standard recommended and minimum required patient questionnaires covering pelvic pain, subfertility, menstrual and reproductive history, medication use and medical history, developed from a comparison of questionnaires used at eight centers and international consultation ^[45]. The aim was to allow data to be combined across centers.

In clinical practice, the evidence on routinely feeding PROM results back to clinicians is broader than endometriosis. A Cochrane review of 116 randomized trials with 49,785 patients, across disciplines including psychiatry, primary care and oncology, found with moderate certainty that PROM feedback probably improves patient-clinician communication (standardized mean difference 0.36) and the recording of diagnoses, and probably improves quality of life slightly (0.15). It probably makes little or no difference to pain (0.00, moderate certainty). The authors noted risk of bias, heterogeneity, and uncertainty about whether the improvements are clinically meaningful or sustained ^[44]. The review summarizes trials across many conditions, so its findings are indirect evidence for pelvic pain.

Where scores and disease findings diverge

A systematic review and meta-analysis of 8 studies (7 using the revised American Society for Reproductive Medicine staging and one using the #Enzian system) examined whether surgical stage tracks pain. Pain intensity did not differ significantly between stage I/II and stage III/IV, although chronic pelvic pain was more frequent in advanced disease. Dysmenorrhea had the highest mean intensity and dysuria the lowest, and heterogeneity was high ^[17]. The review applies to stage as a summary of what was seen at surgery. Pain scores, EHP-30 scores and PBAC scores are about reported experience. They are not measures of lesion extent, and one cannot be converted into the other.

This distinction matters in both directions. A low score on a diary does not demonstrate an absence of disease, and a high score does not describe where disease is or what type it is. Reported symptoms, clinical examination, imaging, surgery and pathology are separate kinds of information.

What this does not tell you

• The research here describes groups, not individuals. A threshold for meaningful change, a PBAC cut-off or a questionnaire average is a statistic about a study sample.
• Most validation work was done in people with confirmed or surgically diagnosed endometriosis who were willing to join a study, often at referral centers ^[6][37][38]. People with suspected but unconfirmed disease, people with adenomyosis alone and people with chronic pelvic pain without endometriosis are less represented, and the available measures for them are fewer and less well validated ^[10][11][33].
• Many of the best-developed diaries were created as trial endpoints and were assessed mainly for content validity. Studies that test them in routine care are limited in the sources reviewed here ^{[3][23][24][25]}.
• No study cited here shows that keeping a diary changes outcomes, shortens the time to a diagnosis or alters a diagnostic or treatment decision in endometriosis, adenomyosis or chronic pelvic pain. The Cochrane evidence on PROM feedback comes from other conditions and shows no change in pain on average ^[44].
• The research does not establish how much effort a record is worth to any one person, and none of it offers advice about what a person should record or how to use a record.
• Scores do not diagnose a condition, do not rank the severity of disease at surgery, and do not replace clinical assessment, imaging or pathology ^[17].
• Findings from other countries, languages and health systems may not transfer. A Norwegian validation of the EHP-30 failed to support some of its scales ^[7], and chart cut-offs vary widely between studies ^[8].

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