Duration of intervals in the care seeking pathway for lung cancer in Bangladesh: A journey from symptoms triggering consultation to receipt of treatment

Timeliness in seeking care is critical for lung cancer patients’ survival and better prognosis. The care seeking trajectory of patients with lung cancer in Bangladesh has not been explored, despite the differences in health systems and structures compared to high income countries. This study investigated the symptoms triggering healthcare seeking, preferred healthcare providers (including informal healthcare providers such as pharmacy retailers, village doctors, and “traditional healers”), and the duration of intervals in the lung cancer care pathway of patients in Bangladesh. A cross-sectional study was conducted in three tertiary care hospitals in Bangladesh among diagnosed lung cancer patients through face-to-face interview and medical record review. Time intervals from onset of symptom and care seeking events were calculated and compared between those who sought initial care from different providers using Wilcoxon rank sum tests. Among 418 study participants, the majority (90%) of whom were males, with a mean age of 57 ±9.86 years, cough and chest pain were the most common (23%) combination of symptoms triggering healthcare seeking. About two-thirds of the total respondents (60%) went to informal healthcare providers as their first point of contact. Living in rural areas, lower levels of education and lower income were associated with seeking care from such providers. The median duration between onset of symptom to confirmation of diagnosis was 121 days, between confirmation of diagnosis and initiation of treatment was 22 days, and between onset of symptom and initiation of treatment was 151 days. Pre-diagnosis durations were longer for those who had sought initial care from an informal provider (p<0.05). Time to first contact with a health provider was shorter in this study compared to other developed and developing countries but utilizing informal healthcare providers caused delays in diagnosis and initiation of treatment. Encouraging people to seek care from a formal healthcare provider may reduce the overall duration of the care seeking pathway.


Abstract:
Introduction: Timeliness in seeking care is critical for lung cancer patients' survival and better prognosis. This study investigated the symptoms triggering healthcare seeking, preferred healthcare providers, and the duration of intervals in the lung cancer care pathway of patients in Bangladesh.

Methods:
A cross-sectional study was conducted in three tertiary care hospitals in Bangladesh among diagnosed lung cancer patients through face-to-face interview and medical record review. Time intervals from onset of symptom and care seeking events were estimated and compared between those who sought initial care from different providers using Wilcoxon rank sum tests. Results: Among 418 study participants, the majority (90%) of whom were males, with a mean age of 57 ±9.86 years, cough and chest pain were the most common (23%) combination of symptoms triggering healthcare seeking. About two-thirds of the total respondents (60%) went to informal healthcare providers as their first point of contact. Living in rural areas, lower levels of education and lower income were associated with seeking care from such providers. The median duration between onset of symptom to confirmation of diagnosis was 121 days, between confirmation of diagnosis and initiation of treatment was 22 days, and between onset of symptom and initiation of treatment was 151 days. Pre-diagnosis durations were longer for those who had sought initial care from an informal provider (p<0.05). Conclusion: Time to first contact with a health provider was shorter in this study compared to other countries but utilizing informal healthcare providers caused delays in diagnosis and initiation of treatment. Creating awareness of lung cancer symptoms and encouraging people to seek care from a formal healthcare provider may reduce the overall duration of the care seeking pathway.

Methods:
29 A cross-sectional study was conducted in three tertiary care hospitals in Bangladesh among 30 diagnosed lung cancer patients through face-to-face interview and medical record review. Time 31 intervals from onset of symptom and care seeking events were estimated and compared between 32 those who sought initial care from different providers using Wilcoxon rank sum tests. 33 Results:

34
Among 418 study participants, the majority (90%) of whom were males, with a mean age of 57 35 ±9.86 years, cough and chest pain were the most common (23%) combination of symptoms 36 triggering healthcare seeking. About two-thirds of the total respondents (60%) went to informal 37 healthcare providers as their first point of contact. Living in rural areas, lower levels of education 38 and lower income were associated with seeking care from such providers. The median duration 39 between onset of symptom to confirmation of diagnosis was 121 days, between confirmation of 40 diagnosis and initiation of treatment was 22 days, and between onset of symptom and initiation 41 of treatment was 151 days. Pre-diagnosis durations were longer for those who had sought initial 42 care from an informal provider (p<0.05).

44
Time to first contact with a health provider was shorter in this study compared to other countries 45 but utilizing informal healthcare providers caused delays in diagnosis and initiation of treatment. 46 Creating awareness of lung cancer symptoms and encouraging people to seek care from a formal 47 healthcare provider may reduce the overall duration of the care seeking pathway.

49
Lung cancer is an aggressive disease with poor survival. As the leading cause of cancer death, 50 it has a higher incidence and mortality rate than any other cancer globally [1]. According to the 51 World Cancer Report 2020, there were 2.1 million new cases and 1.8 million deaths in 2018 due 52 to lung cancer. Early stage diagnosis of lung cancer may allow surgical resection, the most 53 effective treatment, with the five-year survival rate being as high as 50-70% [2][3][4] if diagnosed at 54 Stage I. However, around 75% of people present at an advanced stage of their disease [5], where 55 the overall survival is only 10-20% [1] and 1-5% if diagnosed at Stage IV [2][3][4]. 56 Timeliness is an important dimension of health care quality. The importance of timely diagnosis 57 and treatment of lung cancer, and the need for indicators to measure timeliness of care are 58 increasingly discussed in the literature. Guidelines for lung cancer management include 59 recommended timeframes for the intervals from one timepoint to another in the disease care 60 pathway. British Thoracic Society guidelines [6] suggested the timeframe from diagnosis to 61 treatment commencement should be a maximum of four weeks for chemotherapy, seven weeks 62 for radiotherapy, and eight weeks for surgery. However, in Australia any definitive treatment 63 (surgery, chemotherapy or radiotherapy) should be commenced within two weeks of diagnosis [7] 64 and in Denmark, the recommendation is two weeks for surgery, 15 days for radiotherapy and 11 65 days for chemotherapy [8]. In the USA, recommendations are that treatment should commence 66 within six weeks of diagnosis [9]. Despite recommended consensus of best practice for diagnosis and treatment in guidelines, time from the onset of symptoms to diagnosis, on which prognosis is 68 highly dependent, appears to vary widely in practice. A study in the USA found that the median 69 interval from onset of symptom to diagnosis was 180 days [10], while a systematic review 70 reporting studies from Canada, Sweden, France, Spain, and Norway found the time from 71 symptom onset to initiation of treatment ranged widely from 47 to 138 days [11]. The same time 72 span was 194 days in a study conducted in India [12]. 73 Patients with lung cancer may present with a variety of symptoms which are not unique to that 74 condition. Symptoms of lung cancer include haemoptysis, cough, breathlessness, hoarseness of 75 voice, decreased appetite, weight loss, and fatigue. However, in recent years haemoptysis is 76 reported less and cough and breathlessness are reported more as prominent symptoms [13]. The 77 presence of comorbidities with similar symptoms can make the underlying cancer even more 78 difficult to detect [14]. Sometimes, symptoms are misattributed to smoking or to comorbidities 79 such as chronic obstructive pulmonary disease (COPD) or cardiac diseases, resulting in delayed 80 care-seeking [15]. 81 The majority of lung cancer guidelines have been developed and tested for well-resourced health 82 systems and most of the studies on timeliness of seeking care of patients with lung cancer were 83 conducted in developed countries. Little is known about the lung cancer journey among patients 84 navigating health systems in low and middle income countries (LMIC), although a scoping review 85 reported patients' reluctance in reporting symptoms, a shortage of pulmonary specialists, 86 misdiagnosis, multiple physician consultations and long wait times due to a lack of capacity of 87 health systems as contributing to longer intervals between symptom presentation and lung cancer 88 diagnosis and care in LMICs [16]. 89 Bangladesh is one of the most densely populated LMICs with a population of 163 million people 90 [17] and a GDP per capita of US$ 1,827 [18]. Although only one fifth the size of its neighbour 91 of the population live below the national poverty line [19] and the country has a large rural 93 population of 65% [20]. In Bangladesh, there were over 250,000 premature deaths from 94 noncommunicable diseases in 2018, 26% of which were due to cancer (108,000) [17]. Lung 95 cancer is the most common cancer diagnosis in males in Bangladesh and is the commonest type 96 of cancer-related deaths [21]. Most cases of lung cancer are diagnosed at an advanced stage 97 when the options for treatment are limited [22]. 98 The health system of Bangladesh is structured quite differently from those in Western countries 99 which have informed current understanding of the lung cancer patient journey. There is no 100 In LMICs, informal healthcare providers who lack recognised training comprise a significant 117 portion of the health system, operating generally as individuals rather than via institution [28]. 118 Pharmacies, traditional healthcare providers and village doctors are the common informal 119 healthcare providers in Bangladesh [29]. Pharmacies, which might be more accurately described 120 as retail medicine shops or drug sellers, are often the first point of contact for people in 121 Bangladesh, specifically those from lower socioeconomic status [30]. They are popular for a range 122 of reasons including close proximity to residence, easy accessibility of medicines without going 123 through any investigation, bypassing consultation with qualified healthcare providers primarily due 124 to bypassing out-of-pocket, unregulated, costly consultation fees, accessibility of cheap brands of 125 medicines, pay later credit options, shorter waiting times and longer opening hours compared to 126 public primary care facilities [31]. These pharmacies provide symptomatic treatment and advice 127 on diseases and health conditions and dispense medication without a prescription, despite this 128 being prohibited under the drug licence law [32]. Usually, a pharmacist learns about the specific 129 treatment and management for a health condition by reviewing the prescriptions they receive from 130 any qualified physician, which they apply for patients who bypass consultation with a physician. 131 A country-wide survey of Bangladesh pharmacies revealed only 35% of customers had a 132 prescription for the medication they received. The same survey showed that 51% of the 133 pharmacies were staffed by personnel who had undertaken a three-month pharmacy course to 134 enable them to run the retail shop and 70% of staff had 12 years or less of schooling [33]. In 135 Bangladesh, traditional healthcare providers (ayurvedic, homeopathic, unanie/kabiraji -herbal 136 medicine providers) are also common and popular in rural areas. These traditional healthcare 137 providers have their own medicine preparations which they provide during their consultations. A 138 study suggested that although traditional medicine is popular in both rural and urban areas, 139 inadequate monitoring leads to improper preparation of medicines or even the manufacturing of 140 medicines without legal permission, raising questions about their efficacy [26].
There is an overall lack of evidence in Bangladesh and across the subcontinent regarding 142 timeliness of seeking care of lung cancer patients. For patients with lung cancer in Bangladesh, 143 we currently do not know what symptoms trigger care-seeking, whether care-seeking occurs in a 144 timely way, how long the intervals are between timepoints in the care-seeking pathway, or which 145 healthcare providers are consulted along the lung cancer care pathway. Hence, the aims of this 146 study were to (1)  (AMCGH) is the largest non-profit hospital in the country, currently having a 250-bed inpatient 160 capacity dedicated for cancer care. Patients from across the country receive care from these three 161 hospitals, however, anecdotal evidence suggests that AMCGH receives more patients from 162 higher income groups than the other two hospitals. 163 Inpatients aged ≥18 years with a known diagnosis of lung cancer, who were able to understand 164 the Participant Information and Consent Form and could nominate a family member or carer, if 165 needed, to provide information on their behalf were eligible to participate in the study. Potential 166 participants were identified by doctors or nurses at the study sites from the inpatient files as per 167 the inclusion criteria, after which the investigators approached eligible participants for written 168 informed consent. Eligible participants were given information about the voluntary nature of their 169 involvement in the study, details of the study and contact details of the investigators. The 170 participant information was read to those participants who were illiterate. If the patient was feeling 171 unwell and did not wish to provide answers themselves, patients were asked if they wanted to 172 nominate caregivers to provide data on their behalf, and with consent from patients, caregivers 173 were interviewed separately. Participants provided a signature as a sign of their consent or thumb 174 impression for those who were illiterate. 175 Questionnaire and data collection procedure Bengali with the whole process going through 'translation and back translation' involving two of 180 the investigators and two public health researchers, all of whom were bilingual. The Bengali 181 version of the questionnaire was pilot-tested to ascertain consistency, appropriateness of 182 language, and the best sequence of questions. The questionnaire was pilot-tested with eight lung 183 cancer patients to ensure the questions were understandable and interpreted in a similar way by 184 the participants. Based on the pilot test, several questions were rephrased for better 185 understanding. Participants in the pilot testing were excluded from the final sample for data 186 analysis. The questionnaire collected data under four sections 1) Socio-demographics such as 187 age, sex, residence, education, marital status, type of family, and monthly household income, 2) 188

History of illness 3) Symptoms information including date of onset of symptoms, first symptoms, 189
symptoms that triggered healthcare seeking, 4) Help-seeking practice including choice of healthcare provider for first contact, time to travel to healthcare provider, whether additional 191 healthcare provider consulted before diagnosis, date of diagnosis, time to travel to diagnostic 192 facility, date of referral for treatment, additional healthcare provider consulted after diagnosis 193 before starting treatment, and date of initiation of treatment. 194 The structured questionnaire was administered face-to-face by three data collectors, who were 195 medical doctors, and none was involved in providing treatment to the participants. Two were 196 trained to conduct the survey by the first author who also participated in data collection. 197 Information on different timepoints in the healthcare seeking pathway was collected from hospital 198 clinical files, and from the patient-held clinical files to minimise recall bias. Permission was 199 obtained from the hospital authority and informed consent was sought from the patients to   Table 2 shows the first symptom(s) experienced and the symptoms that led to respondents 267 seeking healthcare. Half of the participants (226, 54%) mentioned just one triggering symptom. 268 However, 46% of the participants reported a combination of symptoms triggering healthcare 269 seeking. At least two symptoms triggered healthcare-seeking in 34% of participants, while 11% 270 of participants mentioned three or four symptoms as their triggering factor. Table 3 shows the 271 most frequent single triggering symptom and most common combination of triggering symptoms. 272 *as multiple triggering symptoms were reported by a single respondent, the total number is more than 418.

274
% are calculated as a proportion of the total sample.

277
The majority of participants (60%) had contact with an informal healthcare provider (pharmacy 278 43%, village doctor or traditional healer 17%) as their first point of contact, whilst 22% went to a 279 General Practitioner (GP) and the remainder to other formal healthcare providers (Table 4). Only 280 8% of the participants sought care from a single provider before undergoing confirmation of a lung 281 cancer diagnosis of lung cancer. The majority (92%) went to multiple healthcare providers before 282 getting confirmation of their lung cancer diagnosis. Two-fifths consulted two additional healthcare 283 providers (42%), one quarter consulted one additional healthcare provider and 81 (19%) 284 respondents consulted three additional healthcare providers pre-diagnosis. After first contact, 285 most of the additional pre-diagnosis care seeking was with public healthcare providers (76%) and 286 specialists (48%) ( Table 4). 287 and additional pre-treatment consultation (1%) timepoints (Table 4). 297 At the first point of contact, the majority of participants in all age groups (60% overall) visited 298 informal healthcare providers which included pharmacies or drug sellers, village doctors and 299 traditional medicine practitioners compared to formal healthcare providers i.e., medically trained 300 personnel. Rural participants were more likely to visit informal providers (61%) and just over half 301 (54%) of the urban participants went to formal healthcare providers as their first point of contact. 302 Most of the participants with little or no education went to informal healthcare providers (67%), 303 and participants with bachelor degree or higher visited formal healthcare providers (71%). 304 Participants with higher income went to formal healthcare providers as their first contact (67%), 305 while 69% of the lower income group went to informal healthcare providers. There were significant 306 differences between first contact with a provider and area of residence, education, and monthly 307 income (p-value <0.05) ( Table 5). 308

310
The median duration of intervals between first contact with provider and diagnosis, onset of 311 symptoms to diagnosis, and onset of symptoms to initiation of treatment were significantly higher 312 among patients who sought care from informal providers as their first point of contact compared 313 to formal healthcare providers (p value <0.05). However, the median duration of interval between 314 onset of symptoms and first contact with provider was shorter in those who visited informal 315 providers compared to formal healthcare providers (p value <0.05) ( Table 6). 316 317 The entire care pathway was segmented in seven intervals. The median time between onset of 320 symptom and initiation of treatment was 151 days. As a segment, the longest duration in the care 321 seeking pathway was the duration from symptom to diagnosis (median 121 days) and the second 322 longest duration was from first contact with any healthcare provider to diagnosis (median 107 323 days). The shortest duration was observed between diagnosis and referral for treatment (median 324 3 days) and onset of symptom to first contact with any healthcare provider (median 10 days) 325 ( Figure 1). 326 Turkey (median 57 days) [11]. These findings suggest that there may be weaknesses in the health 336 system and the way care is currently provided to patients with lung cancer in Bangladesh, as well 337 as individual factors that could be contributing to unacceptable delays. 338 Some of the intervals appeared to be shorter than those observed in studies from other countries. 339 The mean duration between onset of symptoms and first care seeking was 15.2 ± 24.4 (median 340 10) days in this study. This is shorter than time periods reported from symptom onset to contact 341 with a medical doctor in other countries, including 71 days in Nepal [37], 94 days in India [16], 342 and 35 days or 49.9 ± 96.9 days in Turkey [11,38]. In this study, informal healthcare providers were the first choice for seeking healthcare reported by most respondents (60%), hence this 344 duration is shorter than other studies mentioned above. Studies conducted in LMICs have 345 reported that, closer vicinity, easier access, and affordability are the main reasons that patients 346 seek care from informal healthcare providers compared to formal healthcare providers [28]. reported that people will self-medicate or use local remedies before seeking healthcare from a 352 medically trained professional [39]. In a study on acute respiratory illness 62% of people who had 353 cough, fever, running nose, myalgia, or a sore throat sought to treat themselves and pharmacies 354 were the first point of contact for 90% of the respondents [40]. 355 The period from onset of symptoms to confirmed diagnosis was longer than in other countries 356 where similar studies were conducted. In our study the mean duration between onset of 357 symptoms and diagnosis was 151 ± 132 days with a median of 121 days. This is longer compared 358 to studies conducted in India (median of 107 days) [34], Greece (median of 52 days) [36], Turkey 359 (median of 49 days) [11], and Canada (median of 90 days) [41]. As noted above, this difference 360 may reflect the inclusion of pharmacies as the first healthcare provider. This is supported by the 361 finding that the mean duration in our study from first contact with any healthcare provider to 362 diagnosis was longer than other studies (135.8 ± 126.7 days). In Nepal, this step took 50 days on 363 average [37] where the first contact was a medically trained provider. This interval involves the 364 patient reaching qualified doctors and the hospital system, and suggests that the sooner the 365 patient gets diagnosed, the sooner the treatment initiates. In order to ensure early diagnosis, it is 366 paramount that patient's healthcare seeking should start from medically trained provider rather 367 than informal healthcare. 368 It is noteworthy to mention that the delay occurred in the early phase of the disease care pathway, 369 mostly in the pre-diagnosis phase, and after diagnosis the intervals became shorter compared to 370 pre-diagnosis intervals. The mean interval from diagnosis to initiation of treatment was 35.3 ± 371 42.9 days with a median of 22 days in this study. Although it was not within the acceptable 372 maximum timeframe for diagnosis to initiation of treatment described in guidelines in Australia, 373 Denmark and Sweden (14 days), it was within an acceptable range for guidelines in the USA (42 374 days) and the UK (48 days). Further, the duration (diagnosis to initiation of treatment) in this study 375 was shorter than the same interval reported in the USA (median of 27 days) [42] and mean of 376 24.4 ± 54.9 days) [38] and was within the range for medians of 6-45 days reported by Jacobsen 377 et al [43]. 378 The pattern in the duration of intervals between key timepoints in the care seeking pathway for 379 lung cancer in this study suggests that the reason for the duration from onset of symptoms to 380 initiation of treatment was long as care seeking mostly started from informal healthcare in 381 Bangladesh. There were significant differences in timepoints according to whether first contact 382 was with informal healthcare providers compared with formal. While the median duration from 383 onset of symptoms to first contact was significantly shorter for those who used informal providers, 384 intervals between onset of symptoms and diagnosis and treatment were significantly longer for 385 people who sought help from informal providers. Moreover, those who sought care from informal 386 providers were more likely from rural areas, had fewer years of education and a lower income. 387 Similar findings were reported in other studies conducted in Bangladesh [44,45] and India [46]. 388 A study reporting reasons to use over the counter medicines in India and Nepal identified financial 389 constraints, non-availibility of health professionals and increased health care cost to be the major 390 cause [47]. This might be a possible explanation of the finidng in our study as the majority of 391 respondents sought care from pharmacies as their first contact. In addition, traditional healing 392 practice is very widely used in rural Bangladesh, with 75-80% of the rural population dependent