Title: What 'outliers' tell us about missed opportunities for TB control: a cross-sectional study of patients in Mumbai, India

Transcription

1 Author's response to reviews Title: What 'outliers' tell us about missed opportunities for TB control: a cross-sectional study of patients in Authors: Anagha Pradhan (anp @yahoo.com) Karina Kielmann (karina.kielmann@lshtm.ac.uk) Himanshu Gupte (himanshu.gupte@gmail.com) Arun Bamne (arun.bamne@rediffmail.com) John DH Porter (john.porter@lshtm.ac.uk) Sheela Rangan (sheelarangan@gmail.com) Version: 2 Date: 5 March 2010 Author's response to reviews: see over

2 Authors response to comments from the editor and reviewers We are grateful for the positive and extensive comments received from the three anonymous reviewers and hope that the revised manuscript meets their queries and suggestions. A point-bypoint response is provided below. Comments from the Editor Please also clarify in the manuscript whether the study was approved by an appropriate ethics committee, also documenting the full name of the committee. The study was approved by the Institutional Ethics Committee of the Maharashtra Association of Anthropological Sciences, Pune, India and the Institutional Review Board of the London School of Hygiene and Tropical Medicine, London, UK. We have added this sentence in the Methods section of the manuscript. Please avoid mention of patients' names in the manuscript (see the comments of referee 1). Names of patients used in the manuscript are pseudonyms as is common practice in qualitative studies. We have clearly mentioned this in the methods section. Please define all abbreviations the first time they appear. Please also define 'TB' in the abstract and avoid abbreviations (TB) in the title. Changes have been made accordingly, with the following abbreviations defined in the text: TB (tuberculosis), PP (private practitioners), AFB (Acid-fast bacilli), DOT (directly observed treatment). As DOTS is a brand name since 2005, we have not spelt it out, but chosen to add in an explanatory sentence in the Background section, as follows: The RNTCP uses DOTS, the World Health Organisation's TB control strategy since 1995 (branded in 2005) that relies on a standardised regimen administered under direct observation of patients. (Ref: Comments from Referee 1 4. Does the manuscript adhere to the relevant standards for reporting and data deposition? In general it does. In a sense, it departs from general rules for manuscripts in providing names for respondents (which, presumably, are fictitious according to the description in Methods). We have used pseudonyms in order to humanise the patients referred to and add to the readability of the manuscript. This is common practice in qualitative studies.

3 6. Are limitations of the work clearly stated? The additional contribution (focusing on outliers) is well explained but there is little discussion of the limitations of doing this. We strongly believe that the focus on outliers has more merits than limitations, particularly in the absence of another inexpensive method for exploring the reasons that some TB patients never reach the national programme. Nonetheless, we acknowledge two assumptions, which we have now made mention of in a section on limitations added in the discussion section: We have presumed that outliers and the missed out patients share socio-demographic, economic and cultural characteristics, but are unable to verify this assumption Since the term outliers is relative to the rest of the sample, the cut-off value is influenced by the delays as reported by the respondents. We were unable to verify these reports due to lack of documented evidence of help-seeking in private clinics (prescription, case sheets etc) with the patients. Discretionary Revisions (which are recommendations for improvement but which the author can choose to ignore) 1. Background: Para 2, Sentence 2: DOTS is an acronym and needs to be spelled out (true for a number of such acronyms used throughout the paper - DOT, PP, etc). All abbreviations other than DOTS have been explained.. 2. Patient delay: Age is not a socio-economic but rather a demographic variable. The sentence has been changed to read: These respondents showed wide variation in most sociodemographic and economic characteristics such as age, education and employment status. 3. Patient delay: '...were not statistically different...' should read '...the difference between the outliers and the rest of the respondents was not statistically significant...' This sentence has been changed according to the reviewer s suggestion. 4. Patient delay, second paragraph: a series of names is given. One assumes that these are fictitious names, judging from the methods section declaration that confidentiality was maintained. Even so, it is not obvious why respondents should be referred to by their names. Instead, the authors could indicate 'a 60-year old male respondent...'

4 As explained above, the names used are pseudonyms to humanise the experiences of outlier patients and refer back to them in the discussion and conclusion section. Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 5. Background, First sentence: 'Mumbai's...' should read 'India's...', as it refers to '...the world's largest...'. Alternately, the sentence could read, 'Mumbai's tuberculosis control services are an illustration of India's...' The sentence has been changed to read: Mumbai s Revised National Tuberculosis Control Programme (RNTCP) is a shining illustration of the Indian national tuberculosis (TB) control programme, the world s largest and reportedly highly successful national TB control programme. In 2008, the Mumbai programme enrolled more than 30,000 patients with a case detection rate of 85% and cure rate of 87%. 6. Sentence 4: by definition, 3 to 5% of patients would lie between the 96th and 100th percentiles. This sentence needs to be reworded. The sentence has been changed to read: For each of these four indicators of access to TB care, three to five percent of the patients experience delays that fall between the 96 th and 100 th percentile values for respective delay variables. 7. Methods: The authors indicate the basis of their sample size calculation but provide none of the assumptions used in arriving at the size selected. The following sentences have been added in the Methods section: In the selected wards, the DOT centres were classified into low, medium, and high based on their contribution to the ward-level case load. In the selected wards, the DOT centres were classified into low, medium, and high based on their contribution to the ward-level case load. A stratified random sampling method was used to select DOT centres from each ward. All patients from each of the selected DOT centre who had completed between 6 and 16 doses were included in the study. 8. Data management: This section gives a series of outcomes that should be moved to the Results section of the paper (reference to table 1, individuals excluded) The section providing outcomes has been moved to the Results section.

5 9. Patient profile: 'Median per capita income...' Should specify per unit of time (annual? monthly? Weekly?) This has been changed to median monthly per capita income Provider delay: The statement at the top of page 11 '...Help-seeking in the private sector...' is an opinion rather than a result. The sentence has been modified to read: For the outliers, help-seeking in the private medical sector adversely affected access to TB care. 11. Discussion, second paragraph: The actual figure of the median income is a 'result' rather than discussion. The sentence could simply state that the households were below the poverty line without giving the figure (which belongs in results). The sentence has been modified by deleting the figure to read: The outliers came from households with a median per capita income which is below the poverty line [27]. Major Compulsory Revisions (which the author must respond to before a decision on publication can be reached) 12. Data management: There is no description of how the quality of the data was assured (i.e. double data entry, corrections for discordances, etc) All interview schedules were manually checked by two data entry supervisors; the data were manually coded and entered on code sheets. Every 5 th record from the code sheets was checked by a pair of researchers for coding errors. Data were entered by a data entry operator, and 20% of the forms were randomly selected for cross-checking against the code sheets. We have added the following sentence in the data management section: Twenty percent of all data entry forms were cross-checked for coding and data entry errors independently by two researchers. 13. Patient delay: The authors note that 75% of respondents had accessed care prior to the completion of the period that defines a 'suspect' and that should have initiated the diagnostic examination. How was this period (from onset of symptoms until the end of the 'latent' period that defines a suspect) used in defining delay? (In principle, the 'person-time-at-risk' should have commenced only at the end of the 'latent' period). This is not a key point as the study defined the group with the longest delay as the group of interest.

6 In the case of TB, as with other diseases that have a gradual onset, patients often find it difficult to state the exact time of onset of symptoms. The study on which this paper is based used reported data for all delay variables. The senior researchers and clinicians consulted in the design of the study agreed that although patients may report seeking treatment immediately or within a couple of days of the onset of symptoms, in reality, they are likely to present when symptoms are severe enough to affect wellbeing and daily routines. As a result, we decided not to exclude the period of 21 days from the reported help-seeking pathway. We also did not collect information on whether the patient had been in contact with a known case of TB before being diagnosed with TB. This additional information might have partially explained why some patients sought treatment within 21 days of onset of treatment, as contacts of known cases of TB are instructed by health care providers to report immediately if they have any symptoms suggestive of TB. In the revised paper, we have made mention of this point in the paragraph on limitations that has been included in the Discussion section. 14. Provider delay: This is where the concept of 'latent period' needs to be considered - if the respondent sought care before the end of the period that defines a suspect, by policy, the patient should not have been referred for sputum smear examination. Thus, 'provider delay' is only relevant commencing at the end of the period defining a 'suspect' in need of sputum smear examination. Again, this is not an issue with the identification of the outliers but is relevant in terms of the summary results for the whole group presented in the text. This is a technically valid point, however, as stated in response to the point 13 (above), this study used reported data for delays that were not verified against any case records etc. Data on delays between onset of symptoms and diagnosis at Microscopy Centres (MC) under the RNTCP were available for 166 of the 266 patients included in the study. Analysis showed that 16% (27/166) of patients were diagnosed with TB at Microscopy Centres within 21 days of reported onset of symptoms and 11/27 were diagnosed with TB before they reached the microscopy centre (see figure 1 for details). This confirms that that clinical practice regarding TB suspicion in a high prevalence population (as is represented by Mumbai city) varies from the ideal programmatic situation. Clinicians often suspect TB based on their experience and other clinical as well as social characteristics aspects of the patient and appear not to rely exclusively on the reported duration of onset of symptoms. We have therefore have not excluded the period of first 21 days since onset of symptoms from analysis for delays.

7 Figure 1 n=266 Data available on duration between onset of symptoms and diagnosis at MC (n=166) Data not available on duration between onset of symptoms and diagnosis at MC (n=100) Diagnosed at MC within 21 days of onset of symptoms (n=27) Diagnosed at MC after 21 days of onset of symptoms (n=139) Diagnosed outside MC within 21 days (n=11) Diagnosed outside MC within 21 days (n=21) Diagnosed outside MC after 21 days (n=38) Information not available (n=16) Information not available (n=100) Reviewer's report -3 Minor Essential Revisions Introduction 1. Revise the case detection and treatment success rates with the latest data from WHO (Global TB Report 2009). Do ALL smear-positive TB cases submit follow-up sputum samples at the end of intensive phase of treatment as well as at 5 month and at the end of treatment? If that is not the case, please report treatment success rate, not cure rate. We have added in data from the 2009 report. 2. What do PPs stand for; private practitioners? Describe the abbreviation the first time you use it. All abbreviations have been explained the first time, as mentioned above.

8 Methods 3. In this section, please focus just on the methodology. The valid number of cases available for analysis and Table 1 should be moved to the results section. Table 1 has been moved to the results section % of patients were excluded from analysis, especially for provider delay on the grounds that the responses were not detailed enough. I would like to see the characteristics of those excluded from analysis. Cases were excluded from analysis of provider delay when the respondent could not give information about number of days for which s/he took treatment from each provider and the gaps in terms of time periods between seeking care from one provider to the next. Some of these respondents could furnish other data such as the number of providers consulted, number of provider contacts etc. We have appended two separate files for the Reviewer s perusal containing (1) relevant data for those excluded from analysis for provider delay; and (2) frequency tables of socio-demographic variables for those excluded from analysis for at least one delay variable. Results 5. Patient delay: Can you provide the stats for the significant difference in per capita income? We do not claim that the difference was significant. The chi-square test was inconclusive because of the small sample size. p value of chi-square (0.060) added in the text. 6. Don t draw conclusions in the results section; describe the results. Help seeking in private medical sector can adversely affect access to TB care... such statements should go into the discussion section or should be rephrased to describe what happened. The sentence has been modified to read: For the outliers, help-seeking in the private medical sector adversely affected access to TB care. Discussion 7. The discussion reads well. The conclusion should be limited to one paragraph and the rest of the material in this section should go to the discussion section. We have included a short section on limitations in the discussion, beginning with Difficulties faced by the outliers... and limited the conclusion to one paragraph.

9 8. The discussion seems to put much blame on the private sector. However, this should also be seen as an opportunity to strengthen collaborative efforts. Patients would prefer to go through this sector, and that is an indication that people, even those with extremely low income, are willing to spend more for a better service. We have referred to people s preference for the private sector in the background as well as discussion sections. The paper does not blame the private sector. On the contrary, we make a plea for strengthening partnerships with the private sector

10 Appendix 1: Relevant data for those excluded from analysis for provider delay Provider delay Up to 95 th percentile Number of providers visited before Microscopy Centre (MC) Beyond 95 th percentile Excluded from analysis n=188 n=9 n=69 Mean (Range) 2 (1-7) 2 (1-4) 3 (0 6) Number of contacts with providers before MC n=188 n=9 n=69 Mean (Range) 4 (1 12) 4 (2 9) 5 (0 18) Duration of treatment before MC (days) n=188 n=9 n=30 Median (Range) 11 (1 161) 69 (13 213)* 18 (2 50) * Kruskal Wallis Test, p=.026 Period of no-treatment before MC (days) n=188 n=9 n=17 Median (Range) 11 (0 166) 194 (8 736)* 2 (0 28) *Kruskal Wallis Test, p=.000 Total cost of help-seeking before MC (Rs.) n=169 n=6 n=36 Median (Range) 330 ( ) 1375 ( ) 520 ( ) Kruskal Wallis Test, p=.089 Cost of help- seeking before MC as a percentage of PCI (%) n=122 n=4 n=25 Median (Range) ( ) ( ( ) ) Mean Note: Percentages are calculated on valid responses.

11 Socio-demographic profile Sex of the Patient Total Excluded percentile Outliers Total Female Count Col % 36.2% 41.5% 77.8% 41.4% Male Count Col % 63.8% 58.5% 22.2% 58.6% Count Col % 100.0% 100.0% 100.0% 100.0% Age of the patient Excluded percentile Outliers Total Total Count Mean Median Mode Std Deviation Minimum Maximum Marital Status of the Patient Total Excluded percentile Outliers Total Unmarried Count Col % 49.3% 38.8% 22.2% 41.0% Married Count Col % 49.3% 54.3% 66.7% 53.4% Separated Count 2 2 Col % 1.1%.8% Deserted Count Col %.5% 11.1%.8% Widow/widower Count Col % 1.4% 4.8% 3.8% Not asked Count 1 1 Col %.5%.4% Count Col % 100.0% 100.0% 100.0% 100.0%

12 Per capita income (Rs) Total Excluded percentile Outliers Total Upto Rs. Count Col % 75.6% 76.2% 60.0% 75.6% More than Count Rs Col % 24.4% 23.8% 40.0% 24.4% Count Col % 100.0% 100.0% 100.0% 100.0% Educational status Total Excluded percentile Outliers Total Illiterate + Std Count to 4th Col % 44.9% 32.4% 77.8% 37.2% Std 5 to 10 Count Col % 46.4% 58.5% 22.2% 54.1% Other Count Col % 8.7% 9.0% 8.6% Count Col % 100.0% 100.0% 100.0% 100.0% Family type - Recoded Total Excluded percentile Outliers Total Nuclear Count Col % 48.3% 47.2% 28.6% 46.9% Joint or Extended Count Col % 40.0% 42.1% 57.1% 42.0% Single / All male / Staying Count with colleagues Col % 11.7% 10.7% 14.3% 11.1% Count Col % 100.0% 100.0% 100.0% 100.0%

13 Pathway - recoded 2 Total Excluded percentile Outliers Total Only public sector Count used Col % 6.7% 11.2% 9.7% Only private sector Count used Col % 28.3% 45.7% 44.4% 41.6% Public and private Count sector used Col % 65.0% 43.1% 55.6% 48.6% Count Col % 100.0% 100.0% 100.0% 100.0% Excluded percentile Outliers Total Duration of stay More than Count at present 2 years Col % 75.4% 76.6% 77.8% 76.3% address Upto two Count years Col % 24.6% 23.4% 22.2% 23.7% Total Count Col % 100.0% 100.0% 100.0% 100.0% Total Duration of stay at present address Excluded percentile Outliers Total Count Mean Median Mode Std Deviation Minimum Maximum

14 Excluded percentile Outliers Total Number of 0 or 1 earner Count earners - Col % 56.5% 49.2% 22.2% 50.2% recoded More than 1 Count earners Col % 43.5% 50.8% 77.8% 49.8% Total Count Col % 100.0% 100.0% 100.0% 100.0%

15 Appendix 2: Socio-demographic profile of patients excluded from analysis for at least one delay variable Valid Cumulative Frequency Percent Valid Percent Percent Excluded Included Total Sex of the Patient Valid Cumulative Frequency Percent Valid Percent Percent Female Male Total

16 Valid Age of the Patient Cumulative Frequency Percent Valid Percent Percent Total

17 Marital Status of the Patient Valid Cumulative Frequency Percent Valid Percent Percent Unmarried Married Deserted Widow/widower Total Valid Employment status of the respondent Cumulative Frequency Percent Valid Percent Percent Employed Unemployed Student Other Total Valid Per capita income (Rs) Cumulative Frequency Percent Valid Percent Percent Upto Rs More than Rs Total Missing System Total Valid Educational status Cumulative Frequency Percent Valid Percent Percent Illiterate + Std 1 to 4th Std 5 to Other Total Valid Family type - Recoded Cumulative Frequency Percent Valid Percent Percent Nuclear Joint or Extended Single / All male / Staying with colleagues Total Missing System Total