/ . biosoc. Sci. (1977) 9, 107-120
THE STATISTICAL ANALYSIS OF MENSTRUAL BLEEDING PATTERNS* ROBERT SNOWDEN Family Planning Research Unit, University of Exeter {Received \Oth July 1967) Introduction
This report is of a meeting which took place in March 1976 at the Family Planning Research Unit, University of Exeter. The meeting took the form of a 3-day Workshop and was concerned specifically with the statistical analysis of menstrual bleeding patterns. The seventeen participants to the Workshop were all researchers or clinicians who have experience in designing studies on the assessment of menstrual blood loss, the collection and processing of data, and/or the analysis and interpretation of such data. They came from a number of organizations and institutions and represent a wide variety of professional and academic interests in the subject of menstruation. The participants are listed at the end of this report. The notes which follow are based on the discussions which took place during the workshop and on the background papers which were, circulated among participants in advance of the meeting. General background to the study of menstruation
One basic theme throughout the Workshop concerned the relationship between menstrual and intermenstrual bleeding and the use of contraceptive methods. The study of social, cultural and psychological factors affecting the adoption and continued use of contraceptive methods has become increasingly important in recent years in the assessment of family planning programmes. The intrauterine device (IUD), the oral contraceptive and the injectable contraceptive have been, and still are, the most frequently used fertility regulating methods in family planning programmes throughout the world. They are relatively simple to store and to administer, and are among the most effective methods of contraception currently available; like most methods of fertility regulation used in family planning programmes they are female oriented. One common attribute of each of the major female oriented methods is that they produce changes in the pattern of genital bleeding and menstruation. The Workshop participants were keen to develop an agreed approach to the measurement of bleeding patterns in order to facilitate the examination of such * Report of a Workshop held in the University of Exeter, England, March 1976 107
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changes. Another use of such an approach is in the evaluation of gynaecological treatment for pathological bleeding patterns. It is not only users of modern contraceptive methods who experience changes in bleeding patterns. At the present time there are no agreed parameters or definitions relating to the incidence of menstrual or intermenstrual bleeding. This interferes with the assessment of new contraceptive products and makes the comparison of different groups of women and different gynaecological treatments difficult to evaluate. The usual terms relating to bleeding (menstrual, withdrawal, breakthrough, intermenstrual) are often confused by research workers, physicians and women themselves when using some modern contraceptive methods. An estimation of what constitutes a 'cycle'—the usual basis for the evaluation of bleeding patternshas become increasingly difficult and more subjective as newer oral and injectable preparations have become available. In order to evaluate more easily the incidence of bleeding among women using contraceptive methods a more rigorous method of analysis is required. The purpose in holding the Workshop was to discuss ways of using the commonly available data on menstrual blood loss to identify a number of characteristics of such loss so that comparisons can be made between women and for the same woman over time. Background to the Workshop Attempts to develop a statistical model for the analysis of bleeding patterns have been made in recent years. The Workshop incorporated the most significant approaches developed by those concerned in the clinical testing of new contraceptive products, by individuals and by international agencies concerned with the development and use of contraceptive technology in large scale family planning programmes. The principal manufacturers and distributors of oral contraceptives in the UK have, since 1972, been co-operating with the Family Planning Research Unit in the University of Exeter to establish uniform procedures and definitions in the collection of data relating to oral contraceptive clinical trials. It is felt that a standardized method of data collection would improve the quality of data obtained and enable comparisons to be made between preparations by manufacturers and by those attempting to interpret findings at research level. One of the most important issues discussed concerns the assessment and interpretation of bleeding patterns associated with the use of oral contraceptives. Other non-UK companies involved in the testing of contraceptive preparations have also been concerned with the assessment of bleeding patterns. The Exeter Workshop acted as a vehicle for these researchers by permitting the sharing of experience and the discussion of possible approaches to the subject. The second approach provided by individuals has also been very significant. Much of this individual effort has not been published with the exception of the paper by Rodriguez, FaundesLatham & Atkinson (1976). The Workshop brought together a number of these individuals with the intention of producing a coherent statement concerning the areas of agreement and those of continuing uncertainty. Most, but not all, of these individuals are experienced statisticians.
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International agencies concerned with family planning programmes have also become increasingly concerned with the analysis of bleeding patterns among those using specific contraceptive preparations. Representatives of the Population Council, the International Fertility Research Programme, Battelle, and the World Health Organization also attended the Workshop. One significant development in recent years has been a large scale study on menstruation. At a 1973 meeting of the WHO Task Force on Acceptability of Fertility Regulating Methods (part of the WHO Expanded Programme in Human Reproduction), it was recommended that multi-national social science research be initiated on patterns and perceptions of menstrual bleeding. The purpose of this research would be to guide biomedical scientists in the development of new and improved contraceptive methods, by providing 'cultural specifications' regarding the changes in menstrual bleeding patterns which would be acceptable (or unacceptable) to women in various socio-cultural settings. At subsequent WHO meetings the objectives and strategy of the proposed project were further refined. It was considered necessary to develop a statistical model for the evaluation of menstrual bleeding patterns. This model should be capable of handling data from the twelve-country menstruation study, and should also be available for the analysis of menstrual data collected in other research projects. Objectives of the Workshop
In any discussion concerned with the quantification of bleeding patterns it is important to distinguish between the amount or volume of loss and the duration or period of time during which such loss occurs. A stated volume of blood loss in a relatively short period of time is very different from a similar volume of loss taking place over a much longer period of time in terms of the effect on the behaviour of the person concerned. Neither is the relationship between volume and duration of blood loss a simple one, especially when the concepts of regularity and predictability are introduced. A further consideration is the relationship between the blood loss and other concomitant symptoms perceived by the women concerned. These symptoms vary in type and intensity and may be associated with pain, other vaginal discharge, psychological states (e.g. pre-menstrual tension) and pain or discomfort in various parts of the body. The question of perception of blood loss and symptoms associated with such loss leads to the basic difficulty in all discussions concerned with the analysis of menstrual bleeding patterns. On the one hand there is a clear need for the objective measurement of blood loss but on the other it is the subjective interpretation of such loss which determines the behaviour of the individual concerned. This subjective interpretation—or perception—of blood loss is particularly important if the resulting behaviour is associated with the continued use of specific contraceptive methods. The techniques employed in the measurement of blood loss will vary depending on the type of enquiry being made. These techniques vary from highly objective methods to those generally considered to be highly subjective. At one extreme there are the techniques used to quantify the exact amount of blood collected on
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menstrual tampons and pads by the use of sophisticated laboratory measurements; at the other are the techniques dealing with subjective data which are often heavily psychological in content. The laboratory studies of actual blood loss are very specialized, very expensive and not generally available to those concerned with the effect of blood loss on the use of contraceptive methods. Even if such facilities were available it could be argued that it is not the actual amount of blood loss that is important in determining the continued use of specific contraceptive methods but the perceived consequences of such loss. The time-consuming studies of the perceived consequences of changes in blood loss patterns are equally unrealistic in the clinical evaluation of contraceptive preparations. Most studies have concentrated on one or other of these extreme positions—the problem remains of relating objective measurement to subjective interpretation in a realistic way. One method of reconciling these apparently conflicting approaches is to develop a prospective system of data collection which requires a low level of technology and where the data are comparatively easy to obtain. This method involves the completion of a daily record to indicate whether or not vaginal bleeding has occurred. In many respects this approach is unsatisfactory for it is more concerned with the duration than with the amount of blood loss. Nevertheless, the Workshop participants, while agreeing that some attempt should be made to assess the subjective estimation of the amount of blood lost, indicated that the main emphasis should be placed on those factors associated with the duration of loss. This emphasis reflects the need for simplicity while at the same time providing objective data which can be evaluated. The Workshop participants agreed to the following objectives for the 3 days of discussion: (a) To discuss and, if possible, reach agreement on the parameters which are considered to be important in the interpretation of menstrual bleeding patterns. (b) To agree on a definition of terms that shall be used in the statistical analysis of such bleeding patterns. (c) To recommend a common analytical approach to the interpretation of bleeding patterns which may be used by researchers concerned with this topic. This Workshop was therefore principally concerned with reaching agreed definitions for the various units of information requiring analysis. It also considered differences between statistical techniques for data analysis and presentation of the results. If general acceptance for these definitions and procedures is found it is felt there might be an improvement in the comparability of results from different studies and in the general quality of information concerning the patterns of menstrual bleeding. Data collection methods The two most common methods of collecting information on bleeding patterns involve the completion of a daily record or a survey type questionnaire by the
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woman concerned. These methods are usually independent of each other but both approaches are occasionally used in the same study. The daily record The daily record has distinct methodological advantages in that information is recorded at short regular intervals and is therefore less exposed to memory bias. It is also possible to construct a pattern of blood loss for the woman completing the record over time. A major disadvantage of the method is the assumption that the record has been kept conscientiously, especially in those situations where keeping such records is not usual. Nevertheless, if there is a need to study the duration of blood loss in a simple way, the daily record appears to be the most realistic and efficient method. The daily record of blood loss should take the form of a calendar diary card and be so designed as to permit one entry to be made for each calendar day. In the WHO twelve-country study of menstruation, daily records are being kept for illiterate women by a second person called 'a recorder' who holds the records of eight respondents and makes a daily visit to record whether or not bleeding had occurred since the visit the day before. It is important that daily records should not be completed retrospectively after intervals of more than a day. Survey data The collection of data relating to menstrual bleeding patterns by means of interview or a survey type questionnaire permits a large amount of data to be collected in a relatively short period but the validity and reliability of such data remain doubtful. This method, by definition, is concerned with retrospective data and some regard the problems of recall and reporting as insurmountable. The Workshop discussed this issue and concluded that despite the dangers of relying on data collected in this way, some advice could be given in an attempt to reduce the severity of some of these dangers. Two types of survey material should be identified. There is the 'once-only' study which concentrates on a large sample of the population to be studied and which relies exclusively on the collection of one set of data. An alternative approach is to collect data from the same respondents at pre-set intervals. This type of study is most commonly undertaken among those who attend a family planning clinic at known intervals. Both these approaches suffer from the problem of memory bias. The longer the interval between the occurrence and the reporting of an event, the worse this problem becomes. The problem becomes worse when the event to be reported is one or more of a series of similar events. For this reason, the Workshop participants agreed that the most that could be expected would be a description of the most recent episode of bleeding. By obtaining the dates when the last menstrual period commenced and ended, it is possible to infer the mean interval during which bleeding does not occur provided a large enough sample has been obtained. The successful use of such truncated data depends on the variability of time in the menstrual cycle when the information is collected across the sample as a whole. If a respondent is bleeding at the time of being questioned, 8*
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information relating to her last completed incidence of bleeding should be obtained. This would provide more reliable information about the bleeding-free interval. The following operational questions are suggested in relation to this bleedingfree interval: (i) On what day did your last menstrual period begin? (ii) For how many days did it last ? (iii) (Questions relating to volume of blood loss to be asked here; see below), (iv) Was this the last time you bled or had spotting ? (a) If 'no' when was the last time you bled or had spotting? (b) For how many days did it last ? (c) If bleeding now, when was the last day of your last bleeding experience? It is therefore possible to determine to some extent the variability in bleeding patterns across a sample of women using a survey approach. But this gives no information about the variability for the same woman over time unless very regular surveys are to be undertaken using the same women as respondents. The survey approach may be less accurate but it need not be totally disregarded for it could act as a valuable supplement to the more accurate information arising from a daily record. Volume of blood loss On this point, the information given on simple diary cards and collected in general or clinic surveys has been confined to a description of the days on which bleeding has—or has not—occurred. The emphasis has been exclusively on the duration of bleeding and has totally ignored the question of the volume of loss. This has been deliberate for it is in the estimation of the volume of blood loss that subjective interpretation becomes a major difficulty. Most researchers are aware of the problems of describing a recent incident of menstrual bleeding as 'light', 'moderate' or 'heavy'. What do these terms mean and with what is the respondent making a comparison? The use of such terms— which are in common use in clinical research at the present time—is likely to lead to spurious information for they have different meanings for each investigator and each respondent. To the present time no reports have been published which show a high correlation between perceived blood loss and objective measurement of such loss (through the measurement of haemoglobin content extracted from tampons and pads) or with haematological changes (through the occurrence of negative iron balance). One distinction between levels of blood loss which may be more reliable relates to the effect of such loss on the use of menstrual protection. This, then, is not just a perceptual distinction but one that has led to behaviour of some kind. There are three such levels: (a) where bleeding occurs but is perceived as being so light that no menstrual protection is used; (b) where menstrual protection is used satisfactorily; (c) where the menstrual protection used either breaks down or is considered to be inadequate to contain theflowof blood. This approach provides a quantitative description for the two extremes of spotting and flooding
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(or haemorrhaging); with a broad middle band of variation which will incorporate the light, moderate and heavy descriptions currently being used. There is comparatively little difficulty in defining the extremes of spotting and flooding in those cultures where menstrual protection is commonly used but some problems do remain in describing these events where menstrual protection is not normally used. Nevertheless these extremes are an important consideration in the acceptability of contraceptive methods and their incidence should be recorded. The widely variable middle band is difficult to describe with precision. To help matters, it is suggested that the respondent is requested to compare the bleeding episode under discussion with her own previous menstrual experience. This should relate to her perception of her usual blood loss. It is recommended that the following questions are asked which will permit the development of a 5-point scale based on the three levels described above: 1. Was your (last) period: (a) more than usual in amount? (b) the same as usual in amount? (c) less than usual in amount? 2. If answer is 'more than usual in amount' (la) Was your period so heavy that your usual menstrual protection (e.g. pads, tampons, cloths) was inadequate to prevent overflow? Yes/No 3. If answer is 'less than usual' (lc) Did you need to use any menstrual protection ? Yes/No The scale obtained would read: (i) More than usual in amount—flooding—protection inadequate. (ii) More than usual in amount—not flooding—protection adequate, (iii) Same as usual in amount, (iv) Less than usual in amount—protection used. (v) Less than usual in amount—spotting—no protection used. The Workshop participants were aware of some of the weaknesses in these descriptions but felt that they were an advance on the descriptions currently being used. Bleeding pattern analysis The most fundamental question relates to the concept of the menstrual cycle. Evidence was presented which confirmed the view held by most of the Workshop participants that the concept of an easily definable menstrual cycle is largely a myth. The cycle variation between women is so great that comparative assessment is extremely difficult. There are also different definitions of what constitutes a cycle. Some investigators estimate the interval between the timing of bleeding they consider to be menstrual. Episodes of bleeding occurring between the menstrual bleeds are classed as intermenstrual bleeding. In contrast to these relatively
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long cycles, other investigators treat the interval between the beginning of any two consecutive bleeding episodes as a cycle. Both these approaches are based on arbitrary and often unrealistic estimates. Only in the case of the treatment cycle of combined pills where a pattern is arbitrarily imposed can the concept of cycle be easily applied to the data. Nevertheless, there is a strongly held view that bleeding pattern analysis which does not relate to a 28-day cycle will not receive general acceptance. Investigators concerned in trials of some oral contraceptives, such as those which contain a combination of oestrogen and progestogen, firmly believe that it is not practicable to abandon cycle analysis. The question of the control of breakthrough bleeding was considered to be almost as important as the prevention of pregnancy. The concept of a cycle is also one that is in common use and is generally understood. It was stressed that the alternative form of analysis which is concerned with the sequence of bleeding and non-bleeding days does not necessarily preclude the imposition of a cycle. If cycles are, in fact, present this alternative method of analysis will expose them. However, the method itself does not follow the usual form of cyclical analysis. Definitions For convenience this alternative method of bleeding pattern analysis will be called reference period analysis to distinguish it from cyclical analysis. Reference period This refers to the period of time measured in number of days on which analysis is to be based. The duration of the reference period makes little difference to the statistical analysis provided the number of days is sufficient to provide a pattern of bleeding and non-bleeding days. It was finally agreed that a 90-day reference period would be recommended as the most suitable interval. This could be reduced to 60 days and increased by multiples of 30 days if necessary. It is recommended that only studies using the same reference period should be compared. The reference period should begin with the first day on which bleeding is recorded for women not commencing contraceptive therapy and the first day of bleeding following commencement of such therapy for those who are. Data relating to women who do not bleed for any reason should be excluded from analysis. The calendar record This is the daily record card on which the bleeding and non-bleeding days are recorded. The record may contain more days than the reference period or may even contain more than one reference period. Definition of bleeding There was considerable discussion about the definition of bleeding. Most published studies make a distinction between bleeding and spotting which is based on whether or not some form of menstrual protection is used. In those cases where some bleeding is recorded but is so light in amount that protection is not used the blood loss is classed as spotting. Such a distinction is meaningless in those cultures
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where menstrual protection is not normally used. There are also women who are very unlikely to notice what some Western women would refer to as spotting. Despite these limitations, the category of spotting should be retained as a subcategory of bleeding where such a distinction can be justified. Whether a day on which spotting occurs is treated as a bleeding or a non-bleeding day will seriously affect the described pattern of blood loss and therefore a clear statement as to how spotting has been classified will be a necessary requirement in any study report. In those situations in which a distinction between spotting and bleeding can be justified, three symbols only should appear on the calendar record. (a) O = where no bleeding or spotting has occurred; (b) S = where only spotting has occurred; (c) B = where bleeding only or bleeding and spotting has occurred. It is confusing and undesirable to record other symptoms on the daily record. It is recognized however that in field trials of oral contraceptives it might be necessary to record the taking of tablets on a daily basis. Definition oftday> The basic unit of time is to be a day but this interval may not directly relate to calendar days. The interval should be one of 'about 24 hours' and should be consistent in its time of starting and finishing. Minor variation in the 24-hr interval should not create difficulties in the analysis of the data. The Workshop participants considered bedtime-to-bedtime to be a realistic suggestion for defining the beginning and end of this 24-hr period but that local circumstances may require some modification. Bleeding day A day on which bleeding is recorded as having occurred. If spotting and bleeding take place on the same day, the day is classed as a bleeding day. Episode One or more consecutive days during which blood loss has been entered on the calendar record. Each episode is bounded by bleeding-free days. Interval One or more consecutive days during which blood loss has not been reported on the calendar record. Each interval is bounded by bleeding days. The calendar record will therefore consist of a series of bleeding episodes and bleeding-free intervals. Segment A segment consists of one bleeding episode and the immediately following bleeding-free interval. It is recognized that the term 'segment' is not entirely satisfactory owing to its connection with life table analysis but a more suitable alternative was not found. There was considerable discussion about the problem of 1-day or very brief episodes and intervals which may be part of a wider episode or interval. There might be a case for treating 1-day episodes and intervals separately from those of
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greater length. If each day of spotting is included as bleeding in an analysis, the whole system becomes heavily loaded with short bleeding-free intervals, thus biasing the mean bleeding-free interval and segment length to the shorter end of the range. A further comment about this is made below. Elementary measures to be used in analysis From the information collected on the calendar record a number of variables can be identified and quantified for any group of women over a reference period. These relate to the number, mean duration, longest duration and variability of episodes, intervals and segments. Variability is indicated by the standard deviation of episodes, intervals and segments but it is really a measure of spread. Table 1 lists the measures considered. From these seventeen measures, the Workshop participants concluded that the nine measures marked with an asterisk would provide the basic information necessary for analysis bearing in mind the need to keep measures as few in number and as simple as possible. These nine measures are: (a) The number of bleeding days within the defined reference period. (b) The number of bleeding episodes within the defined reference period. (c) The average duration of the bleeding episodes within the defined reference period. (d) The variability in the length of the bleeding episodes within the defined reference period. (e) The duration of the longest bleeding episode within the defined reference period. (f) The longest bleeding-free interval within the defined reference period. (g) The average duration of the segments within the defined reference period, (h) The variability in the length of the segments within the defined reference period, (i) The number of spotting days within the defined reference period. The measure giving the number of spotting days is included primarily because it is information which is used widely by those conducting contraceptive trials. In those situations where the distinction between bleeding and spotting cannot be mainTable 1. Possible measures relating to days, episodes, intervals and segments within each reference period No. of bleeding days No. of spotting days
* * Episodes
No. Average length Distribution (SD) Range: minimum Range: maximum
Interval
* * * *
Segment * *
*
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tained, this measure should be ignored. Whether spotting is treated as a subset of bleeding or non-bleeding in the calculation of episodes, intervals and segments is discussed below but it should be emphasized that spotting is not to be treated as a separate characteristic other than in the calculation of total days on which it occurs within the defined reference period. The choice of which measures to omit and which to include has been made on the basis of the interpretation to be placed on the results. The principal interest is in the bleeding rather than non-bleeding patterns and for this reason it is recommended that information concerning bleeding days and episodes should receive priority. It is also necessary to present the information obtained in the most helpful manner possible. It is clear, for example, that information on the average duration of bleeding episodes is required but knowledge of the variability in episode length may be equally important. The assessment of episode and segment variability is particularly relevant in the predictability of menstrual bleeding patterns by the woman concerned. The predictability of the number of bleeding days in any one episode is also a useful parameter in assessing the acceptability of specific contraceptive methods. The final list of measures was selected to meet as many of these research eventualities and uses as considered relevant by the Workshop participants. They are not independent of each other and should be considered together. Undoubtedly several correlations can be made and the Workshop participants agreed that a multivariate technique should be used when comparing the effect of two contraceptive products on the bleeding patterns of those taking part in the study. In the evaluation of contraceptive methods, a two-sample multivariate test for the eight variables should be applied. The investigator can then pick out features of the bleeding patterns which show the greatest differences in the effects of the two products. If a multivariate approach is adopted computer facilities will probably be required, but the measures described can be easily obtained by individuals without recourse to such facilities. This is one of the strengths of the reference-period approach when compared to cyclical analysis. Appropriate test statistics can be calculated for hypotheses concerning comparisons of two or more contraceptive methods using these variables. Interpretation by other interested parties will be aided if significance levels are indicated where these are relevant. Treatment of incomplete episodes and intervals at the end of the reference period One problem that arises at analysis concerns those bleeding episodes or bleeding-free intervals which are incomplete at the end of the reference period. It is necessary to develop rules to determine whether or not events occurring immediately after the end of the reference period should be included in the analysis. The Workshop participants discussed this topic at length as the occurrence of an incomplete episode or interval will be present in every case. Three alternative strategies were discussed: (a) To exclude any event occurring after the end of the reference period and to exclude any incomplete episode or interval appearing in the data.
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(b) To include the number of bleeding days if an incomplete episode occurs at the end of the reference period but to exclude this episode in the calculation of average episode or interval length. These strategies are relatively simple to operate but they seriously bias the estimate of averages and variability towards zero. This is not so important if the reference period is a relatively long one (e.g. 180 days and over) but it creates serious problems with the recommended reference period of 90 days. (c) The third strategy is to include some incomplete episodes and intervals but to exclude others according to an agreed procedure. This procedure relies on the development of arbitrary rules designed to reduce bias as much as possible without unduly disturbing the validity of the data. The following procedure is considered the most appropriate. (i) Daily calendar data should be recorded for 21 days following the end of the reference period. (ii) The data recorded for the 20 days following the end of the reference period should be examined. (iii) If the incomplete bleeding episode or bleeding-free interval is completed within these 20 days, the length of the episode or interval should be included in the estimation of average length and variability of length. (iv) If the incomplete episode or interval is still incomplete at the end of the additional 20 days, the episode or interval should be closed at the 20th day. These additional 20 days should be included as if the episode or interval were completed on that day. This strategy does not remove bias completely but it does reduce its effect. In practice, very few episodes or intervals will be incomplete after a further 20 days following the end of the reference period. This problem of truncated data does not appear at the beginning of the diary record as the reference period, by definition, begins on the first day of an episode. The place of'spotting1 records in analysis A decision needs to be taken on whether spotting is to be regarded as bleeding or non-bleeding. Most participants accepted that it would be preferable to include this as non-bleeding owing to the problem of shortening the segment length mentioned above. It was also emphasized that many women do not include spotting in the calendar record unless specifically asked to do so. However, some investigators may like to include an analysis of spotting as part of the bleeding pattern. There would then be a second set of results in which spotting is included either as bleeding or as part of the bleeding-free interval. In any analysis of bleeding where the bleeding-free interval may include spotting days, an indication of the number of spotting days per reference period should be included in the study report. It was also emphasized that spotting should be clearly defined in any report, as the behavioural definition depending on the use of menstrual protection would not apply in all situations.
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Minimum number of respondents Owing to the large number of variables being measured and the high degree of variance between individual women, the workshop participants recommend that the minimum number of respondents in any one reference period should be 100. In studying subgroups within the study population (e.g. women of different parity or age) there should be between 30 and 50 respondents in each group. Such numbers would provide sufficient information to identify the trends distinguishing these groups. Presentation of data The nine variables with the probability values of their differences (where applicable) should be set out in a single table. The use of histograms showing the distribution of these variables was also recommended. Conclusion and summary
The proposed method of bleeding pattern analysis avoids the problem of defining the menstrual cycle. The difficulty of maintaining a cyclical approach becomes acute when methods of fertility regulation are used which are known to disrupt seriously previously experienced bleeding patterns. By using eight simple measures relating to the pattern of bleeding over a fixed period of time, it is possible to present sensitive indicators previously available but not used. These indicators will permit a more meaningful comparison of data obtained from different groups of women or for the same woman over time. The eight measures relate to the number, average duration and variability of bleeding episodes taking place within a defined period of time; the variability of the bleeding-free interval; the average duration and variability of the bleeding episode and its succeeding bleeding-free interval; and the number of days on which bleeding has occurred. Agreement was reached by the Workshop participants regarding the terms to be used, the definition of these terms, the statistical approach to be adopted and the analytical procedures to be followed in the analysis of bleeding patterns. It is hoped that this alternative approach to bleeding pattern analysis will assist researchers, clinicians and other investigators in the collection, analysis and interpretation of menstrual bleeding patterns. An example of this approach is given in the following paper by D. Mayes. This example is based on data in the form of diary cards made available to the Family Planning Research Unit, Exeter University, by John Guillebaud of the Churchill Hospital, Oxford. Acknowledgments
This report has been based on the notes and comments made during discussion at the Workshop. I would especially like to thank John McEwan who made detailed notes and subsequently made these notes available to me. In addition, notes were
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kept by my research colleagues Margaret Williams and Christopher Grossmith. My role as rapporteur should not disguise the amount of work undertaken by participants before, during and after the Workshop sessions. Workshop participants June Bolton Patrick Bye Barbara Christian Gordon Duncan Derek Edwards Ross Erickson Paula Hessian David Mayes John McEwan Jean Robertson German Rodriguez Robert Snowden William Stewart Howard Tatum Michael Thomas Jan Voerman Pramuan Virutamasen
Parke-Davis & Co., UK Schering Chemicals Ltd, UK WHO, Geneva, Switzerland Battelle Population Study Center, USA The Home Office, London, UK Alza Corporation, USA G. D. Searle & Co. Ltd, UK University of Exeter, UK WHO, London, UK John Wyeth & Brother Ltd, UK International Statistical Institute, London, UK University of Exeter, UK Searle Laboratories, USA The Population Council, USA International Fertility Research Program, USA Organon Scientific Development Group, Holland WHO, Thailand
Observers Christopher Grossmith Margaret Williams
Family Planning Research Unit, University of Exeter, UK Family Planning Research Unit, University of Exeter, UK
Background documents MAYES, D.
(1976) Factors in Menstrual Bleeding Patterns. Report prepared for the Exeter Work-
shop. G., FAUNDES-LATHAM, A. & ATKINSON, L.E. (1976) An approach to the analysis of menstrual patterns in the critical evaluation of contraceptives. Stud. Fam. Plann. 7,2. SNOWDEN, R. (1976) The Analysis of Bleeding Patterns. Report prepared for the Exeter Workshop. THOMAS, M.N. (1976) Some Possible Approaches to the Quantification of Menstrual Bleeding. Report prepared for the Exeter Workshop. WORLD HEALTH ORGANIZATION (1973) Acceptability of Fertility Regulating Methods. Report on a planning meeting of the WHO Task Force, March 1973 (ATF-G: 6/3/73). WORLD HEALTH ORGANIZATION (1975) Acceptability of Fertility Regulating Methods on the Statistical Analysis ofBleeding Patterns. Report of a meeting of the WHO Task Force, October 1975 (ATF 13:10/75) RODRIGUEZ,
THE STATISTICAL ANALYSIS OF MENSTRUAL BLEEDING PATTERNS* ROBERT SNOWDEN Family Planning Research Unit, University of Exeter {Received \Oth July 1967) Introduction
This report is of a meeting which took place in March 1976 at the Family Planning Research Unit, University of Exeter. The meeting took the form of a 3-day Workshop and was concerned specifically with the statistical analysis of menstrual bleeding patterns. The seventeen participants to the Workshop were all researchers or clinicians who have experience in designing studies on the assessment of menstrual blood loss, the collection and processing of data, and/or the analysis and interpretation of such data. They came from a number of organizations and institutions and represent a wide variety of professional and academic interests in the subject of menstruation. The participants are listed at the end of this report. The notes which follow are based on the discussions which took place during the workshop and on the background papers which were, circulated among participants in advance of the meeting. General background to the study of menstruation
One basic theme throughout the Workshop concerned the relationship between menstrual and intermenstrual bleeding and the use of contraceptive methods. The study of social, cultural and psychological factors affecting the adoption and continued use of contraceptive methods has become increasingly important in recent years in the assessment of family planning programmes. The intrauterine device (IUD), the oral contraceptive and the injectable contraceptive have been, and still are, the most frequently used fertility regulating methods in family planning programmes throughout the world. They are relatively simple to store and to administer, and are among the most effective methods of contraception currently available; like most methods of fertility regulation used in family planning programmes they are female oriented. One common attribute of each of the major female oriented methods is that they produce changes in the pattern of genital bleeding and menstruation. The Workshop participants were keen to develop an agreed approach to the measurement of bleeding patterns in order to facilitate the examination of such * Report of a Workshop held in the University of Exeter, England, March 1976 107
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changes. Another use of such an approach is in the evaluation of gynaecological treatment for pathological bleeding patterns. It is not only users of modern contraceptive methods who experience changes in bleeding patterns. At the present time there are no agreed parameters or definitions relating to the incidence of menstrual or intermenstrual bleeding. This interferes with the assessment of new contraceptive products and makes the comparison of different groups of women and different gynaecological treatments difficult to evaluate. The usual terms relating to bleeding (menstrual, withdrawal, breakthrough, intermenstrual) are often confused by research workers, physicians and women themselves when using some modern contraceptive methods. An estimation of what constitutes a 'cycle'—the usual basis for the evaluation of bleeding patternshas become increasingly difficult and more subjective as newer oral and injectable preparations have become available. In order to evaluate more easily the incidence of bleeding among women using contraceptive methods a more rigorous method of analysis is required. The purpose in holding the Workshop was to discuss ways of using the commonly available data on menstrual blood loss to identify a number of characteristics of such loss so that comparisons can be made between women and for the same woman over time. Background to the Workshop Attempts to develop a statistical model for the analysis of bleeding patterns have been made in recent years. The Workshop incorporated the most significant approaches developed by those concerned in the clinical testing of new contraceptive products, by individuals and by international agencies concerned with the development and use of contraceptive technology in large scale family planning programmes. The principal manufacturers and distributors of oral contraceptives in the UK have, since 1972, been co-operating with the Family Planning Research Unit in the University of Exeter to establish uniform procedures and definitions in the collection of data relating to oral contraceptive clinical trials. It is felt that a standardized method of data collection would improve the quality of data obtained and enable comparisons to be made between preparations by manufacturers and by those attempting to interpret findings at research level. One of the most important issues discussed concerns the assessment and interpretation of bleeding patterns associated with the use of oral contraceptives. Other non-UK companies involved in the testing of contraceptive preparations have also been concerned with the assessment of bleeding patterns. The Exeter Workshop acted as a vehicle for these researchers by permitting the sharing of experience and the discussion of possible approaches to the subject. The second approach provided by individuals has also been very significant. Much of this individual effort has not been published with the exception of the paper by Rodriguez, FaundesLatham & Atkinson (1976). The Workshop brought together a number of these individuals with the intention of producing a coherent statement concerning the areas of agreement and those of continuing uncertainty. Most, but not all, of these individuals are experienced statisticians.
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International agencies concerned with family planning programmes have also become increasingly concerned with the analysis of bleeding patterns among those using specific contraceptive preparations. Representatives of the Population Council, the International Fertility Research Programme, Battelle, and the World Health Organization also attended the Workshop. One significant development in recent years has been a large scale study on menstruation. At a 1973 meeting of the WHO Task Force on Acceptability of Fertility Regulating Methods (part of the WHO Expanded Programme in Human Reproduction), it was recommended that multi-national social science research be initiated on patterns and perceptions of menstrual bleeding. The purpose of this research would be to guide biomedical scientists in the development of new and improved contraceptive methods, by providing 'cultural specifications' regarding the changes in menstrual bleeding patterns which would be acceptable (or unacceptable) to women in various socio-cultural settings. At subsequent WHO meetings the objectives and strategy of the proposed project were further refined. It was considered necessary to develop a statistical model for the evaluation of menstrual bleeding patterns. This model should be capable of handling data from the twelve-country menstruation study, and should also be available for the analysis of menstrual data collected in other research projects. Objectives of the Workshop
In any discussion concerned with the quantification of bleeding patterns it is important to distinguish between the amount or volume of loss and the duration or period of time during which such loss occurs. A stated volume of blood loss in a relatively short period of time is very different from a similar volume of loss taking place over a much longer period of time in terms of the effect on the behaviour of the person concerned. Neither is the relationship between volume and duration of blood loss a simple one, especially when the concepts of regularity and predictability are introduced. A further consideration is the relationship between the blood loss and other concomitant symptoms perceived by the women concerned. These symptoms vary in type and intensity and may be associated with pain, other vaginal discharge, psychological states (e.g. pre-menstrual tension) and pain or discomfort in various parts of the body. The question of perception of blood loss and symptoms associated with such loss leads to the basic difficulty in all discussions concerned with the analysis of menstrual bleeding patterns. On the one hand there is a clear need for the objective measurement of blood loss but on the other it is the subjective interpretation of such loss which determines the behaviour of the individual concerned. This subjective interpretation—or perception—of blood loss is particularly important if the resulting behaviour is associated with the continued use of specific contraceptive methods. The techniques employed in the measurement of blood loss will vary depending on the type of enquiry being made. These techniques vary from highly objective methods to those generally considered to be highly subjective. At one extreme there are the techniques used to quantify the exact amount of blood collected on
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menstrual tampons and pads by the use of sophisticated laboratory measurements; at the other are the techniques dealing with subjective data which are often heavily psychological in content. The laboratory studies of actual blood loss are very specialized, very expensive and not generally available to those concerned with the effect of blood loss on the use of contraceptive methods. Even if such facilities were available it could be argued that it is not the actual amount of blood loss that is important in determining the continued use of specific contraceptive methods but the perceived consequences of such loss. The time-consuming studies of the perceived consequences of changes in blood loss patterns are equally unrealistic in the clinical evaluation of contraceptive preparations. Most studies have concentrated on one or other of these extreme positions—the problem remains of relating objective measurement to subjective interpretation in a realistic way. One method of reconciling these apparently conflicting approaches is to develop a prospective system of data collection which requires a low level of technology and where the data are comparatively easy to obtain. This method involves the completion of a daily record to indicate whether or not vaginal bleeding has occurred. In many respects this approach is unsatisfactory for it is more concerned with the duration than with the amount of blood loss. Nevertheless, the Workshop participants, while agreeing that some attempt should be made to assess the subjective estimation of the amount of blood lost, indicated that the main emphasis should be placed on those factors associated with the duration of loss. This emphasis reflects the need for simplicity while at the same time providing objective data which can be evaluated. The Workshop participants agreed to the following objectives for the 3 days of discussion: (a) To discuss and, if possible, reach agreement on the parameters which are considered to be important in the interpretation of menstrual bleeding patterns. (b) To agree on a definition of terms that shall be used in the statistical analysis of such bleeding patterns. (c) To recommend a common analytical approach to the interpretation of bleeding patterns which may be used by researchers concerned with this topic. This Workshop was therefore principally concerned with reaching agreed definitions for the various units of information requiring analysis. It also considered differences between statistical techniques for data analysis and presentation of the results. If general acceptance for these definitions and procedures is found it is felt there might be an improvement in the comparability of results from different studies and in the general quality of information concerning the patterns of menstrual bleeding. Data collection methods The two most common methods of collecting information on bleeding patterns involve the completion of a daily record or a survey type questionnaire by the
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woman concerned. These methods are usually independent of each other but both approaches are occasionally used in the same study. The daily record The daily record has distinct methodological advantages in that information is recorded at short regular intervals and is therefore less exposed to memory bias. It is also possible to construct a pattern of blood loss for the woman completing the record over time. A major disadvantage of the method is the assumption that the record has been kept conscientiously, especially in those situations where keeping such records is not usual. Nevertheless, if there is a need to study the duration of blood loss in a simple way, the daily record appears to be the most realistic and efficient method. The daily record of blood loss should take the form of a calendar diary card and be so designed as to permit one entry to be made for each calendar day. In the WHO twelve-country study of menstruation, daily records are being kept for illiterate women by a second person called 'a recorder' who holds the records of eight respondents and makes a daily visit to record whether or not bleeding had occurred since the visit the day before. It is important that daily records should not be completed retrospectively after intervals of more than a day. Survey data The collection of data relating to menstrual bleeding patterns by means of interview or a survey type questionnaire permits a large amount of data to be collected in a relatively short period but the validity and reliability of such data remain doubtful. This method, by definition, is concerned with retrospective data and some regard the problems of recall and reporting as insurmountable. The Workshop discussed this issue and concluded that despite the dangers of relying on data collected in this way, some advice could be given in an attempt to reduce the severity of some of these dangers. Two types of survey material should be identified. There is the 'once-only' study which concentrates on a large sample of the population to be studied and which relies exclusively on the collection of one set of data. An alternative approach is to collect data from the same respondents at pre-set intervals. This type of study is most commonly undertaken among those who attend a family planning clinic at known intervals. Both these approaches suffer from the problem of memory bias. The longer the interval between the occurrence and the reporting of an event, the worse this problem becomes. The problem becomes worse when the event to be reported is one or more of a series of similar events. For this reason, the Workshop participants agreed that the most that could be expected would be a description of the most recent episode of bleeding. By obtaining the dates when the last menstrual period commenced and ended, it is possible to infer the mean interval during which bleeding does not occur provided a large enough sample has been obtained. The successful use of such truncated data depends on the variability of time in the menstrual cycle when the information is collected across the sample as a whole. If a respondent is bleeding at the time of being questioned, 8*
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information relating to her last completed incidence of bleeding should be obtained. This would provide more reliable information about the bleeding-free interval. The following operational questions are suggested in relation to this bleedingfree interval: (i) On what day did your last menstrual period begin? (ii) For how many days did it last ? (iii) (Questions relating to volume of blood loss to be asked here; see below), (iv) Was this the last time you bled or had spotting ? (a) If 'no' when was the last time you bled or had spotting? (b) For how many days did it last ? (c) If bleeding now, when was the last day of your last bleeding experience? It is therefore possible to determine to some extent the variability in bleeding patterns across a sample of women using a survey approach. But this gives no information about the variability for the same woman over time unless very regular surveys are to be undertaken using the same women as respondents. The survey approach may be less accurate but it need not be totally disregarded for it could act as a valuable supplement to the more accurate information arising from a daily record. Volume of blood loss On this point, the information given on simple diary cards and collected in general or clinic surveys has been confined to a description of the days on which bleeding has—or has not—occurred. The emphasis has been exclusively on the duration of bleeding and has totally ignored the question of the volume of loss. This has been deliberate for it is in the estimation of the volume of blood loss that subjective interpretation becomes a major difficulty. Most researchers are aware of the problems of describing a recent incident of menstrual bleeding as 'light', 'moderate' or 'heavy'. What do these terms mean and with what is the respondent making a comparison? The use of such terms— which are in common use in clinical research at the present time—is likely to lead to spurious information for they have different meanings for each investigator and each respondent. To the present time no reports have been published which show a high correlation between perceived blood loss and objective measurement of such loss (through the measurement of haemoglobin content extracted from tampons and pads) or with haematological changes (through the occurrence of negative iron balance). One distinction between levels of blood loss which may be more reliable relates to the effect of such loss on the use of menstrual protection. This, then, is not just a perceptual distinction but one that has led to behaviour of some kind. There are three such levels: (a) where bleeding occurs but is perceived as being so light that no menstrual protection is used; (b) where menstrual protection is used satisfactorily; (c) where the menstrual protection used either breaks down or is considered to be inadequate to contain theflowof blood. This approach provides a quantitative description for the two extremes of spotting and flooding
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(or haemorrhaging); with a broad middle band of variation which will incorporate the light, moderate and heavy descriptions currently being used. There is comparatively little difficulty in defining the extremes of spotting and flooding in those cultures where menstrual protection is commonly used but some problems do remain in describing these events where menstrual protection is not normally used. Nevertheless these extremes are an important consideration in the acceptability of contraceptive methods and their incidence should be recorded. The widely variable middle band is difficult to describe with precision. To help matters, it is suggested that the respondent is requested to compare the bleeding episode under discussion with her own previous menstrual experience. This should relate to her perception of her usual blood loss. It is recommended that the following questions are asked which will permit the development of a 5-point scale based on the three levels described above: 1. Was your (last) period: (a) more than usual in amount? (b) the same as usual in amount? (c) less than usual in amount? 2. If answer is 'more than usual in amount' (la) Was your period so heavy that your usual menstrual protection (e.g. pads, tampons, cloths) was inadequate to prevent overflow? Yes/No 3. If answer is 'less than usual' (lc) Did you need to use any menstrual protection ? Yes/No The scale obtained would read: (i) More than usual in amount—flooding—protection inadequate. (ii) More than usual in amount—not flooding—protection adequate, (iii) Same as usual in amount, (iv) Less than usual in amount—protection used. (v) Less than usual in amount—spotting—no protection used. The Workshop participants were aware of some of the weaknesses in these descriptions but felt that they were an advance on the descriptions currently being used. Bleeding pattern analysis The most fundamental question relates to the concept of the menstrual cycle. Evidence was presented which confirmed the view held by most of the Workshop participants that the concept of an easily definable menstrual cycle is largely a myth. The cycle variation between women is so great that comparative assessment is extremely difficult. There are also different definitions of what constitutes a cycle. Some investigators estimate the interval between the timing of bleeding they consider to be menstrual. Episodes of bleeding occurring between the menstrual bleeds are classed as intermenstrual bleeding. In contrast to these relatively
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long cycles, other investigators treat the interval between the beginning of any two consecutive bleeding episodes as a cycle. Both these approaches are based on arbitrary and often unrealistic estimates. Only in the case of the treatment cycle of combined pills where a pattern is arbitrarily imposed can the concept of cycle be easily applied to the data. Nevertheless, there is a strongly held view that bleeding pattern analysis which does not relate to a 28-day cycle will not receive general acceptance. Investigators concerned in trials of some oral contraceptives, such as those which contain a combination of oestrogen and progestogen, firmly believe that it is not practicable to abandon cycle analysis. The question of the control of breakthrough bleeding was considered to be almost as important as the prevention of pregnancy. The concept of a cycle is also one that is in common use and is generally understood. It was stressed that the alternative form of analysis which is concerned with the sequence of bleeding and non-bleeding days does not necessarily preclude the imposition of a cycle. If cycles are, in fact, present this alternative method of analysis will expose them. However, the method itself does not follow the usual form of cyclical analysis. Definitions For convenience this alternative method of bleeding pattern analysis will be called reference period analysis to distinguish it from cyclical analysis. Reference period This refers to the period of time measured in number of days on which analysis is to be based. The duration of the reference period makes little difference to the statistical analysis provided the number of days is sufficient to provide a pattern of bleeding and non-bleeding days. It was finally agreed that a 90-day reference period would be recommended as the most suitable interval. This could be reduced to 60 days and increased by multiples of 30 days if necessary. It is recommended that only studies using the same reference period should be compared. The reference period should begin with the first day on which bleeding is recorded for women not commencing contraceptive therapy and the first day of bleeding following commencement of such therapy for those who are. Data relating to women who do not bleed for any reason should be excluded from analysis. The calendar record This is the daily record card on which the bleeding and non-bleeding days are recorded. The record may contain more days than the reference period or may even contain more than one reference period. Definition of bleeding There was considerable discussion about the definition of bleeding. Most published studies make a distinction between bleeding and spotting which is based on whether or not some form of menstrual protection is used. In those cases where some bleeding is recorded but is so light in amount that protection is not used the blood loss is classed as spotting. Such a distinction is meaningless in those cultures
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where menstrual protection is not normally used. There are also women who are very unlikely to notice what some Western women would refer to as spotting. Despite these limitations, the category of spotting should be retained as a subcategory of bleeding where such a distinction can be justified. Whether a day on which spotting occurs is treated as a bleeding or a non-bleeding day will seriously affect the described pattern of blood loss and therefore a clear statement as to how spotting has been classified will be a necessary requirement in any study report. In those situations in which a distinction between spotting and bleeding can be justified, three symbols only should appear on the calendar record. (a) O = where no bleeding or spotting has occurred; (b) S = where only spotting has occurred; (c) B = where bleeding only or bleeding and spotting has occurred. It is confusing and undesirable to record other symptoms on the daily record. It is recognized however that in field trials of oral contraceptives it might be necessary to record the taking of tablets on a daily basis. Definition oftday> The basic unit of time is to be a day but this interval may not directly relate to calendar days. The interval should be one of 'about 24 hours' and should be consistent in its time of starting and finishing. Minor variation in the 24-hr interval should not create difficulties in the analysis of the data. The Workshop participants considered bedtime-to-bedtime to be a realistic suggestion for defining the beginning and end of this 24-hr period but that local circumstances may require some modification. Bleeding day A day on which bleeding is recorded as having occurred. If spotting and bleeding take place on the same day, the day is classed as a bleeding day. Episode One or more consecutive days during which blood loss has been entered on the calendar record. Each episode is bounded by bleeding-free days. Interval One or more consecutive days during which blood loss has not been reported on the calendar record. Each interval is bounded by bleeding days. The calendar record will therefore consist of a series of bleeding episodes and bleeding-free intervals. Segment A segment consists of one bleeding episode and the immediately following bleeding-free interval. It is recognized that the term 'segment' is not entirely satisfactory owing to its connection with life table analysis but a more suitable alternative was not found. There was considerable discussion about the problem of 1-day or very brief episodes and intervals which may be part of a wider episode or interval. There might be a case for treating 1-day episodes and intervals separately from those of
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greater length. If each day of spotting is included as bleeding in an analysis, the whole system becomes heavily loaded with short bleeding-free intervals, thus biasing the mean bleeding-free interval and segment length to the shorter end of the range. A further comment about this is made below. Elementary measures to be used in analysis From the information collected on the calendar record a number of variables can be identified and quantified for any group of women over a reference period. These relate to the number, mean duration, longest duration and variability of episodes, intervals and segments. Variability is indicated by the standard deviation of episodes, intervals and segments but it is really a measure of spread. Table 1 lists the measures considered. From these seventeen measures, the Workshop participants concluded that the nine measures marked with an asterisk would provide the basic information necessary for analysis bearing in mind the need to keep measures as few in number and as simple as possible. These nine measures are: (a) The number of bleeding days within the defined reference period. (b) The number of bleeding episodes within the defined reference period. (c) The average duration of the bleeding episodes within the defined reference period. (d) The variability in the length of the bleeding episodes within the defined reference period. (e) The duration of the longest bleeding episode within the defined reference period. (f) The longest bleeding-free interval within the defined reference period. (g) The average duration of the segments within the defined reference period, (h) The variability in the length of the segments within the defined reference period, (i) The number of spotting days within the defined reference period. The measure giving the number of spotting days is included primarily because it is information which is used widely by those conducting contraceptive trials. In those situations where the distinction between bleeding and spotting cannot be mainTable 1. Possible measures relating to days, episodes, intervals and segments within each reference period No. of bleeding days No. of spotting days
* * Episodes
No. Average length Distribution (SD) Range: minimum Range: maximum
Interval
* * * *
Segment * *
*
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tained, this measure should be ignored. Whether spotting is treated as a subset of bleeding or non-bleeding in the calculation of episodes, intervals and segments is discussed below but it should be emphasized that spotting is not to be treated as a separate characteristic other than in the calculation of total days on which it occurs within the defined reference period. The choice of which measures to omit and which to include has been made on the basis of the interpretation to be placed on the results. The principal interest is in the bleeding rather than non-bleeding patterns and for this reason it is recommended that information concerning bleeding days and episodes should receive priority. It is also necessary to present the information obtained in the most helpful manner possible. It is clear, for example, that information on the average duration of bleeding episodes is required but knowledge of the variability in episode length may be equally important. The assessment of episode and segment variability is particularly relevant in the predictability of menstrual bleeding patterns by the woman concerned. The predictability of the number of bleeding days in any one episode is also a useful parameter in assessing the acceptability of specific contraceptive methods. The final list of measures was selected to meet as many of these research eventualities and uses as considered relevant by the Workshop participants. They are not independent of each other and should be considered together. Undoubtedly several correlations can be made and the Workshop participants agreed that a multivariate technique should be used when comparing the effect of two contraceptive products on the bleeding patterns of those taking part in the study. In the evaluation of contraceptive methods, a two-sample multivariate test for the eight variables should be applied. The investigator can then pick out features of the bleeding patterns which show the greatest differences in the effects of the two products. If a multivariate approach is adopted computer facilities will probably be required, but the measures described can be easily obtained by individuals without recourse to such facilities. This is one of the strengths of the reference-period approach when compared to cyclical analysis. Appropriate test statistics can be calculated for hypotheses concerning comparisons of two or more contraceptive methods using these variables. Interpretation by other interested parties will be aided if significance levels are indicated where these are relevant. Treatment of incomplete episodes and intervals at the end of the reference period One problem that arises at analysis concerns those bleeding episodes or bleeding-free intervals which are incomplete at the end of the reference period. It is necessary to develop rules to determine whether or not events occurring immediately after the end of the reference period should be included in the analysis. The Workshop participants discussed this topic at length as the occurrence of an incomplete episode or interval will be present in every case. Three alternative strategies were discussed: (a) To exclude any event occurring after the end of the reference period and to exclude any incomplete episode or interval appearing in the data.
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(b) To include the number of bleeding days if an incomplete episode occurs at the end of the reference period but to exclude this episode in the calculation of average episode or interval length. These strategies are relatively simple to operate but they seriously bias the estimate of averages and variability towards zero. This is not so important if the reference period is a relatively long one (e.g. 180 days and over) but it creates serious problems with the recommended reference period of 90 days. (c) The third strategy is to include some incomplete episodes and intervals but to exclude others according to an agreed procedure. This procedure relies on the development of arbitrary rules designed to reduce bias as much as possible without unduly disturbing the validity of the data. The following procedure is considered the most appropriate. (i) Daily calendar data should be recorded for 21 days following the end of the reference period. (ii) The data recorded for the 20 days following the end of the reference period should be examined. (iii) If the incomplete bleeding episode or bleeding-free interval is completed within these 20 days, the length of the episode or interval should be included in the estimation of average length and variability of length. (iv) If the incomplete episode or interval is still incomplete at the end of the additional 20 days, the episode or interval should be closed at the 20th day. These additional 20 days should be included as if the episode or interval were completed on that day. This strategy does not remove bias completely but it does reduce its effect. In practice, very few episodes or intervals will be incomplete after a further 20 days following the end of the reference period. This problem of truncated data does not appear at the beginning of the diary record as the reference period, by definition, begins on the first day of an episode. The place of'spotting1 records in analysis A decision needs to be taken on whether spotting is to be regarded as bleeding or non-bleeding. Most participants accepted that it would be preferable to include this as non-bleeding owing to the problem of shortening the segment length mentioned above. It was also emphasized that many women do not include spotting in the calendar record unless specifically asked to do so. However, some investigators may like to include an analysis of spotting as part of the bleeding pattern. There would then be a second set of results in which spotting is included either as bleeding or as part of the bleeding-free interval. In any analysis of bleeding where the bleeding-free interval may include spotting days, an indication of the number of spotting days per reference period should be included in the study report. It was also emphasized that spotting should be clearly defined in any report, as the behavioural definition depending on the use of menstrual protection would not apply in all situations.
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Minimum number of respondents Owing to the large number of variables being measured and the high degree of variance between individual women, the workshop participants recommend that the minimum number of respondents in any one reference period should be 100. In studying subgroups within the study population (e.g. women of different parity or age) there should be between 30 and 50 respondents in each group. Such numbers would provide sufficient information to identify the trends distinguishing these groups. Presentation of data The nine variables with the probability values of their differences (where applicable) should be set out in a single table. The use of histograms showing the distribution of these variables was also recommended. Conclusion and summary
The proposed method of bleeding pattern analysis avoids the problem of defining the menstrual cycle. The difficulty of maintaining a cyclical approach becomes acute when methods of fertility regulation are used which are known to disrupt seriously previously experienced bleeding patterns. By using eight simple measures relating to the pattern of bleeding over a fixed period of time, it is possible to present sensitive indicators previously available but not used. These indicators will permit a more meaningful comparison of data obtained from different groups of women or for the same woman over time. The eight measures relate to the number, average duration and variability of bleeding episodes taking place within a defined period of time; the variability of the bleeding-free interval; the average duration and variability of the bleeding episode and its succeeding bleeding-free interval; and the number of days on which bleeding has occurred. Agreement was reached by the Workshop participants regarding the terms to be used, the definition of these terms, the statistical approach to be adopted and the analytical procedures to be followed in the analysis of bleeding patterns. It is hoped that this alternative approach to bleeding pattern analysis will assist researchers, clinicians and other investigators in the collection, analysis and interpretation of menstrual bleeding patterns. An example of this approach is given in the following paper by D. Mayes. This example is based on data in the form of diary cards made available to the Family Planning Research Unit, Exeter University, by John Guillebaud of the Churchill Hospital, Oxford. Acknowledgments
This report has been based on the notes and comments made during discussion at the Workshop. I would especially like to thank John McEwan who made detailed notes and subsequently made these notes available to me. In addition, notes were
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kept by my research colleagues Margaret Williams and Christopher Grossmith. My role as rapporteur should not disguise the amount of work undertaken by participants before, during and after the Workshop sessions. Workshop participants June Bolton Patrick Bye Barbara Christian Gordon Duncan Derek Edwards Ross Erickson Paula Hessian David Mayes John McEwan Jean Robertson German Rodriguez Robert Snowden William Stewart Howard Tatum Michael Thomas Jan Voerman Pramuan Virutamasen
Parke-Davis & Co., UK Schering Chemicals Ltd, UK WHO, Geneva, Switzerland Battelle Population Study Center, USA The Home Office, London, UK Alza Corporation, USA G. D. Searle & Co. Ltd, UK University of Exeter, UK WHO, London, UK John Wyeth & Brother Ltd, UK International Statistical Institute, London, UK University of Exeter, UK Searle Laboratories, USA The Population Council, USA International Fertility Research Program, USA Organon Scientific Development Group, Holland WHO, Thailand
Observers Christopher Grossmith Margaret Williams
Family Planning Research Unit, University of Exeter, UK Family Planning Research Unit, University of Exeter, UK
Background documents MAYES, D.
(1976) Factors in Menstrual Bleeding Patterns. Report prepared for the Exeter Work-
shop. G., FAUNDES-LATHAM, A. & ATKINSON, L.E. (1976) An approach to the analysis of menstrual patterns in the critical evaluation of contraceptives. Stud. Fam. Plann. 7,2. SNOWDEN, R. (1976) The Analysis of Bleeding Patterns. Report prepared for the Exeter Workshop. THOMAS, M.N. (1976) Some Possible Approaches to the Quantification of Menstrual Bleeding. Report prepared for the Exeter Workshop. WORLD HEALTH ORGANIZATION (1973) Acceptability of Fertility Regulating Methods. Report on a planning meeting of the WHO Task Force, March 1973 (ATF-G: 6/3/73). WORLD HEALTH ORGANIZATION (1975) Acceptability of Fertility Regulating Methods on the Statistical Analysis ofBleeding Patterns. Report of a meeting of the WHO Task Force, October 1975 (ATF 13:10/75) RODRIGUEZ,
