Unused, expired pharmaceuticals and their disposal practices among the general public in Burdur-Türkiye: a cross-sectional study

Abstract

Background

Unused pharmaceuticals are currently a public health problem. This study aimed to identify unused pharmaceuticals, research practices about the disposal methods, classify the medicines according to Anatomical Therapeutic Chemical codes (ATC) and, to determine the number of unused medicines.

Methods

The study was designed as a cross-sectional study. Data were collected between April and August 2023 in Burdur-Türkiye by non-probability sampling technique (convenience method). Pharmaceuticals were classified according to ATC. Statistical Package for Social Science SPSS (V.24) package program was used for data analysis.

Results

A total of 1120 people, 1005 in the first sample group and 115 in the second sample group, participated in the study. Findings of first sample group: A total of 4097 boxes of unused pharmaceuticals (4.7 ± 4.3 boxes/per capita) were detected. It was found that pharmaceuticals were stored in areas such as kitchens (59.1%) and refrigerators (38.6%), the reason for keeping them was reuse (41%), and the disposal practice was household garbage (81%). Paracetamol (648 boxes), Other cold preparation (303 boxes), Dexketoprofen (239 boxes), Diclofenac (218 boxes), Amoxicillin and beta-lactamase inhibitor (190 boxes) were found to be the most frequently unused pharmaceuticals. Using the unused medicines at home without consulting a physician was 94.1% (self-medication). Findings of second sample group: Of the 6189 dosage forms in 265 boxes pharmaceutical, 3132(50.6%) dosage forms were used and 3057(49.4%) were found to be unused.

Conclusion

There is a significant amount and number of unused medicines in households, and self-medication is common. Medicines are not properly disposed of and some of them expire. Public information is needed. A “drug take-back system” for unused medicines can be useful in solving this problem.

Introduction

Drugs are agents used in the treatment of diseases and are prescribed by physicians based on the patient’s diagnosis. For home treatment, medications prescribed by physicians are obtained from the pharmacy and used for treatment. However, patients may prematurely discontinue home drug treatment for various reasons. The main reasons for early discontinuation include the early recovery from disease, a change in diagnosis, a decrease in or loss of faith in the treatment, side effects of the medication, and the patient non-compliance with treatment, among others [1]. When the patients discontinue drug treatment for any reason, they may contribute to the accumulation of unused medicines in the household. The unused pharmaceuticals that accumulate in the household can be reused at different times to alleviate the symptoms of various diseases, can be given to another person, or kept on hand until the expiration date [2]. If there is lack of knowledge about the medicines that accumulate in the household, the expiration dates of the medicines may expire, which can lead to health problems when these medicines are used [3].

Several epidemiological studies have been conducted on unused pharmaceuticals. In a study conducted in Saudi Arabia, it was reported that about half of the participants accumulated unused pharmaceuticals in their households, the main reason for accumulation was to cure illness, they disposed of the pharmaceuticals by throwing them in the garbage, and a significant number of participants were uneducated about pharmaceutical disposal practices [4]. In a study conducted by Woldeyohanins et al. (2021), it was reported that more than half of the participants had unused pharmaceuticals in their homes, about 59.2% checked the expiration date, and the household trash can was used as a method of pharmaceutical disposal practices [5]. In a similar study, people were reported to have unused medicines at homes, to store them because they might need them later, and to dispose of them inappropriately [6].

While this is the case in the general public, similar findings have been reported among student in health professions (medicine, nursing, pharmacy, etc.). For example, a previous study reported that 95.7% of pharmacy students had unused medications, some of which were expired and not properly disposed [7, 8]. Improper disposal of pharmaceuticals posed an environmental hazard. The presence of pharmaceutical waste in wastewater treatment plants was indicative of this problem. A study reported that pharmaceutical metabolites and active ingredients were detected in drinking water facilities, even if at low levels [9].

There are numerous studies in the literature on unused medicines. These studies summarize data from different countries, cultures, geographies, and levels of development. In generel, these studies categorize the unused medicines by mechanism of action (antibiotics, analgesics, etc.) rather than by Anatomical Therapeutic Chemical classification (ATC). In addition, it has been observed that the number of studies reporting the amount of used and unused medicines is extremely limited. This gap in the literature needs to be addressed. Therefore, this study aimed to identify unused medications, classify them according to the ATC, research participants’ practices about these medications, and determine how much of medications such as tablets, capsules and dragees with a given quantity are used and how much is unused.

Methods

Study design

The study was designed as a cross-sectional study. Data were collected between April 1 and August 31, 2023 in Burdur-Türkiye. This study consists of two sample groups, the first sample group and the second sample group. The data of both groups were collected by a non-probability sampling technique (convenience method). While the online method (Google form) was used to collect the data in the first sample, the face-to-face method was used in the second sample. For first sample size, proportionally based sampling with the double design effect method was used. For second sample size, certain percentage of the calculated number of participants in the first sample group was taken as a basis. The purpose of the second sample was to determine the quantity of unused pharmaceuticals, to strengthen the findings and to enhance the literature. For some reasons, the data collected from the first sample were not collected from the second sample (Private life/privacy, protection of personal data, difficulty of voluntary participation, similar personal characteristics.etc.).

Participant criteria

Participant criteria were determined to participate in the study. These were determined as not having any chronic disease at the time of data collection and not taking medication for any disease, having appropriate equipment for online data (computer, smartphone, tablet), living at home due to the question types, being literate (for face-to-face data collection), not being given partial or incomplete information, being above the age of 18 years and giving consent. Participant exclusion criteria were defined as not having the above-mentioned conditions and not having unused medicines.

First sample size

A formula (n = Z² x p(1-p)/d² x DEFF (n: sample size, Z:confidence interval, p:expected proportion, d:margin of error and DEFF: design effect)) was used to calculate this sample size [10]. According to this formula (1.96² × 0.5(1–0.5)/0.05² × 2n=754 × 0.1), it was needed that at least 830 people participate in the study. Sociodemographic data, practices on unused medicines, disposal methods, number of unused medicines and generic names of medicines were collected from these sample group.

Second sample size

For the quantity analysis, 10% (n = 83) of the first sample size (n = 830) was taken as a basis [11]. Only the generic name of pharmaceutical and quantity of unused drugs (dosage forms) were collected from this sample.

As a result, it was calculated that at least 913 people participated in the study.

Data collection tool

Since the research consisted of two separate sample groups, two separate forms were used. The data collection form collected from the first sample included the sociodemographic characteristics of the participants, their practices about unused drugs, disposal method, generic names of drugs and the number of unused drugs. In the second sample group data collection form, only data on the quantity of unused medicines such as tablets, dragees and capsules were collected.

Description of unused drug: It is called the leftover part of the drug after treatment. This description was sent as a video to the group for online data collection. It was explained verbally to the face-to-face data collection group.

The data collection form of the first sample group

In order to obtain data from the first sample group of the study, a questionnaire was developed based on the questions of previous studies [11,12,13,14]. The content of this form includes socio-demographics, practices about on unused medicines, disposal practices, number of unused medicines and generic names of medicines. The data collected through this form were collected online by using a Google form. The Google form was turned into a link. This link and the explanation video of the research (purpose, participant criteria, data filling examples, etc.) were sent to people as text messages via WhatsApp. In particular, groups with a large number of people registered (groups such as school, work, etc.) were targeted.

The data collection form of the second sample group

This was a data collection form in which quantity of unused medicines in the medicines box (tablets, dragees, capsules, etc.) was recorded. The number of dosage forms of these medicines was obtained by simple subtraction (Number of dosage forms of unused medicines = number of dosage forms of medicines - number of dosage forms of medicines used). Data used for quantity analysis were collected face-to-face by using a written data collection form.

Classification of Pharmaceuticals

Pharmaceuticals were classified according to the ATC/DDD Index 2023. This index is a very useful resource published by WHO and WHO Collaborating Centre for Drug Statistics Methodology and includes Anatomical Therapeutic Chemical (ATC) classification, Defined Daily Dose (DDD) values, codes [15].

Data Analysis

SPSS (V.24) package program was used for data analysis. Descriptive parameters were summarized as (n) and percentage (%) where relevant [n(%)]. Mean (X̅) and standard deviation (S) were summarized as X̅±S. The relationship between the number of pharmaceuticals in the households and sociodemographic variables was tested with non-parametric tests (Mann Whitney U, Kruskal Wallis, Tamhanes T2). Statistical significance level was taken as p < 0.05.

Results

A total of 1172 people participated in the study, 1057 in the first sample group (52 people were excluded) and 115 in the second sample group. The study was completed with 1120 participants.

The findings of the first sample group (n = 1005)

Some people data were not included in the study due to exclusion criteria (n = 24, 2.3%). The number of people with unused pharmaceuticals was found to be 28(2.6%) (97.4% of participants have unused medicines). Therefore, study was completed with 1005 participants (Age_mean 36.9 ± 12.3 years). A total of 4097 boxes of unused pharmaceuticals were observed (4.7 ± 4.3 boxes/per capita).

When evaluating the number of unused pharmaceuticals and the sociodemographic characteristics of the participants (n = 1005), no statistical difference was observed in gender variable (p = 0.089). However, statistical differences were observed in marital status (lower in singles), place of residence (lower in rural areas), and economic status (Income < Expense) (p < 0.001, p < 0.001, p < 0.001, respectively) as shown in Table 1.

Table 1 The relationship between sociodemographic variables and the number of unused pharmaceuticals (n = 1005)

It was found that the options of kitchen (59.1%) as the room where pharmaceuticals were kept at home, refrigerator (38.6%) as the place where pharmaceuticals were stored, family health center (42.2%) as the health facility where most pharmaceuticals were prescribed, reuse (41%) as the reason for keeping pharmaceuticals in household, family physician (48.7%) as the specialty branch where most pharmaceuticals were prescribed, were selected more than other options. The options of checking the expiry date of pharmaceuticals (72.1%), reading the package insert (56.7%) and not buying pharmaceuticals without a prescription (58.7%) were more chosen ones by the participants. Keeping pharmaceuticals in household until the expiry date (44.6%), throwing expired pharmaceuticals in the garbage (81%), thinking that improper disposal of pharmaceuticals pollutes the environment (74.8%), and The Ministry of Health is responsible for raising awareness on medicines (41.7%) were the options that were more frequently marked by the participants. Using the unused medicines at home without consulting a physician was 94.1% (self-medication). (Table 2).

Table 2 Participants’ practices on pharmaceuticals (n = 1005)

The most unused drugs by ATC class were Lansoprozole, Folic Acid, Propranolol, Other Cicatrizants, Levothyroxine Sodium, Amoxicillin and beta lactamase inhibitor, Dexketoprofen, Paracetamol, Metronidazole, Other Cold Medicines. In terms of number of boxes, it was “Paracetamol, Other Cold Medicines, Dexketoprofen, Diclofenac, Amoxicillin and beta lactamase inhibitor, Pseudoephedrine combination, Lansoprazole and Acetylsalicylic acid” (Table 3).

Table 3 ATC classification of unused pharmaceuticals (Number of participants:1005)

n = number of pharmaceuticals (box), %=percentage of the number of pharmaceuticals. Pharmaceuticals with fewer than 10 were given as “others” in the table. Pharmaceuticals in the Others section was summarized separately as ATC name, ATC code and number of pharmaceuticals (For example: Zinc sulfate(A12CB01):9). A-Others(n = 80):Benzidamine(A01AD02):9, Lactulose(A06AD11):9, Zinc sulfate(A12CB01):9, Nifuroxazide(A07AX03):8, Tioctic acid(A16AX01):7, Pinaverium(A03AX04):6, Sodium fluoride(A01AA01):6, Famotidine(A02BA03):5, Orlistat(A08AB01):3, Rabeprazole(A02BC04):3, Multivitamins and other minerals, incl. combinations(A11AA03):2, Otilonium bromide(A03AB06):2, Multienzymes(lipase, protease etc.)(A09AA02):2, Dexpanthenol(A11HA30):1, Domperidone(A03FA03):1, Glibenclamide(A10BB01):1, Glibornuride(A10BB04):1, Glycerol(A06AG04):1, Magnesium hydroxide(A02AA04):1, Mebeverine(A03AA04):1, Various(A01AD11):1, Pyridoxine(A11HA02):1. B-Others(n = 24):Cyanocobalamin(B03BA01):8, Ferrous amino acid complex and folic acid(B03AD01):7, Clopidogrel(B01AC04):3, Ticagrelor(B01AC24):1, Apixaban(B01AF02):1, Tranexamic acid(B02AA02):1, Ferrous glycine sulfate(B03AA01):1, Ferrous fumarate(B03AA02):1, Cyanocobalamin, combinations(B03BB51):1. C-Others(n = 46):Doxazosin(C02CA04):7, Rosuvastatin(C10AA07):6, Candesartan(C09CA06):4, Nebivolol(C07AB12):3, Amlodipine(C08CA01):2, Captopril(C09AA01):2, Lercanidipine(C08CA13):2, Digoxin(C01AA05):2, Atenolol(C07AB03):1, Benidipin(C08CA15):1, Calcium Dobesilat(C05BX01):1, Organo-heparinoid(C05BA01):1, Hydrocortisone(C05AA01):1, Quinapril and diuretics(C09BA06):1, Lisinopril(C09AA03):1, Losartan and diuretics(C09DA01):1, Olmesartan mdeoxomil and amlodipine(C09DB02):1, Pentoxifylline(C04AD03):1, Pitavastatin(C10AA08):1, Other preparations, combinations(C05AX03):1, Spironolactone(C03DA01):1, Hydrochlorothiazide combinations(C03AX01):1, Torasemide(C03CA04):1, Trimetazidine(C01EB15):1, Valsartan and diuretics(C09DA03):1, Zofenopril(C09AA15):1. D-Others(n = 51):Silver sulfadiazine(D06BA01):8, Centella asiatica herba(D03AX14):7, Carbamide combinations(D02AE51):5, Clobetasol(D07AD01):3, Oxytetracycline(D06AA03):3, Sertaconazole(D01AC14):3, Terbinafine(D01BA02):3, Diphenhydramine(D04AA32):2, Nadifloxacin(D10AF05):2, Wart and anti-corn preparations (D11AF):2, Acyclovir(D06BB03):1, Other antibiotics for topical use (D06AX):1, Betamethasone(D07AC01):1, Butenafine(D01AE23):1, Hydroquinone(D11AX11):1, Hydrocortisone(D07AA02):1, Isotretinoin combinations(D10AD54):1, Clobetasone(D07AB01):1, Methylprednisolone aceponate(D07AC14):1, Mometasone(D07AC13):1, Naftifine(D01AE22):1, Terbinafine(D01AE15):1, Oxiconazole(D01AC11):1. G-Others(n = 9):Clotrimazole(G01AF02):2, Progesterone(G03DA04):2, Dydrogesteron(G03DB01):2, Imidazole derivates and corticosteroids(G01BF):1, Estradiol(G03CA03):1, Darifenacin(G04BD10):1. H-Others(n = 12):Dexamethasone(H02AB02):6, Prednisolone(H02AB06):5, Betamethasone(H02AB01):1. J-Others(n = 31):Cefaclor(J01DC04):8, Azithromycin(J01FA10):5, Clarithromycin(J01FA09):4, Cefixime(J01DD08):3, Doxycycline(J01AA02):2, Cefprozil(J01DC10):1, Sulfamethoxazole and trimethoprim (J01EE01):1, Lincomycin(J01FF02):1, Levofloxacin(J01MA12):1, Fusidic acid(J01XC01):1, Fluconazole(J02AC01):1, Rifamycin(J04AB03):1, Aciclovir(J05AB01):1, Valaciclovir(J05AB11):1. L-Others(n = 1):Leflunamide(L04AA13):1 M-Others(n = 37):Acemetacin(M01AB11):7, Thiocolchicoside, combinations(M03BX55):7, Preparations with salicylic acid derivatives(M02AC):5, Colchicine(M04AC01):5, Phenprobamate, combinations excl. psycholeptics(M03BA51):2, Thiocolchicoside(M03BX05):2, Indomethacin(M01AB01):2, Meloxicam(M01AC06):2, Benzidamine(M02AA05):1, Etofenamate(M02AA06):1, Piroxicam(M02AA07):1, Methocarbamol, combinations excl. psycholeptics(M03BA53):1, Tizanidine(M03BX02):1. N-Others(n = 34):Paracetamol, combinations with psycholeptics(N02BE71):8, Sertraline(N06AB06):5, Eletriptan(N02CC06):3, Frovatriptan(N02CC07):2, Paroxetine(N06AB05):2, Methylphenidate(N06BA04):2, Flunarizine(N07CA03):2, Acetylsalicylic acid, combinations excl. psycholeptics(N02BA51):1, Ergotamine(N02CA02):1, Topiramate(N03AX11):1, Gabapentin(N0BF01):1, Lacosamide(N03AX18):1, Diazepam(N05BA01):1, Escitalopram(N06AB10):1, Trazodone(N06AX05):1, Duloxetine(N06AX21):1, Lamotrigine(N03AX09):1. R-Others(n = 52):Oxymetazoline(R01AA05):10, Salbutamol and sodium cromoglicate (R03AK04):7, Cyproheptadine(R06AX02):4, Oxolamine(R05DB07):3, Rupatadine(R06AX28):3, Diphenhydramine(R06AA2):2, Beclomethasone(R01AD01):2, Mometasone(R01AD09):2, Fluticasone(R03BA05):2, Theophylline(R03DA04):2, Montelukast(R03DC03):2, Ebastine(R06AX22):2, Fexofenadine(R06AX26):2, Levodropropizine(R05DB27):2, Xylometazoline(R01AA07):1, Azelastine(R01AC03):1, Pseudoephedrine(R01BA02):1, Formoterol and budesonide(R03AK07):1, Formoterol and beclometasone(R03AK08):1, Doxylamine(R06AA09):1, Bilastine(R06AX29):1. S-Others(n = 13):Fusidic acid(S01AA13):3, Ketotifen(S01GX08):3, Tobramycin(S01AA12):2, Artificial tears and other indifferent preparations(S01XA20):2, Gentamicin(S03AA06):2, Corticosteroids and antiinfectives in combination(S01CA01):1 (Table 3)

The findings of the second sample group (n = 115)

It was found that there were 265 boxes (6189 dosage forms in the boxes) of unused pharmaceuticals (3.8 ± 5 boxes/per capita) in in households of these participants. Of the 265 boxes medicines, 74(27.9%) were found to be expired. The most Pseudoephedrine combination (23 boxes) and Other cold preparation (23 boxes) and Dexketoprofen (20 boxes) drugs were found to be unused drugs. The percentage of unused drugs was highest in class D(79%), P(55.4%) and N(54.6%), while used drugs were in class G(76.9%), C(69.6%) and A(53.9%) (Table 4).

Among the prescribed pharmaceuticals, pharmaceuticals in “Class G” were the most commonly used (76.9%), while pharmaceuticals in “Class D” were the least used (21%). The highest number of unused pharmaceuticals was found to be in “Class R” (929 dosage forms), followed by “Class M” drugs (682 dosage forms). Of the pharmaceuticals prescribed to the participants (6189 dosage forms), 3132(50.6%) were used and 3057(49.4%) were unused (Table 4).

Table 4 An analysis of unused pharmaceuticals (Number of participants = 115)

Discussion

Many studies have been conducted on unused medicines and their disposal practices. According to the findings of these studies, there is a serious public health problem and lack of policy. This study presents the current situation in Türkiye. In our study, there was a statistical difference between the number of unused drugs and some sociodemographic characteristics such as marriage, education, economic status etc. In the literature search, studies researching socio-demographic characteristics and the number of pharmaceuticals are very limited. A previous study found that medication disposal practice was found to be associated with some sociodemographic variables such as gender, age, marital status, and residence [16]. In another study, it was reported that parameters such as gender, education level, and place of residence were associated with drug keeping at home [17]. Therefore, it is possible to say that some sociodemographic characteristics are effective on the dependent variables.

According to the findings obtained from the participants’ practices on unused pharmaceuticals, it was found that pharmaceuticals were generally stored in the kitchen and refrigerator, and most of the pharmaceuticals were prescribed by primary health care facilities and family physicians. Addition, it was found that the most important reason for having unused pharmaceuticals in their households was reuse (for treatment), 44.6% kept them in household until the expiration date, 72.1% checked the expiration date, 56.7% read the package insert, and 41.3% purchased pharmaceuticals without a prescription. The findings that expired pharmaceuticals were thrown away, that improper disposal of pharmaceuticals polluted the environment and that the awareness on pharmaceuticals should be raised by the Ministry of Health came to the forefront. In a study reported by Manocha et al. (2020), it was reported that a significant proportion of participants had unused pharmaceuticals in their households and threw away expired pharmaceuticals [18]. In a study conducted by Althagafi et al. (2022), it was shown that about half of the participants were found pharmaceuticals in their households and that these pharmaceuticals were mainly stored in the refrigerator [4]. In another study researching the storage conditions of pharmaceuticals, it was shown that pharmaceuticals were stored in many different places, but especially in the kitchen [19]. In a study conducted by Gidey et al. (2020), it was reported that improper disposal of pharmaceuticals might be harmful to the environment and 77.4% disposed of pharmaceuticals by throwing them in household garbage [20]. In another study on medication disposal, it was reported that participants mostly disposed of medicines by throwing them in household garbage [21]. The dominant view was that unused pharmaceuticals were generally accumulated in households, expired pharmaceuticals were thrown in household garbage, pharmaceuticals were stored in the kitchen, and improper disposal harmed the environment in literature. When we compare the findings in the literature with our study findings, it is possible to say that the findings are similar. We think that the variation in the findings of behaviors towards unused medicines (storage, disposal, etc.) may be related to the type of study, number of participants, participant characteristics, culture, region and development level of the country.

According to the findings of our study, there were unused drugs in almost all ATC classes. In addition, the most prominent drugs in the quantity of leftover drugs were analgesics (paracetamol, etc.), cold medicines, NSAIDs (dexketoprofen, etc.), antibiotics (amoxicillin, etc.) and proton pump inhibitors (lansoprazole, etc.). According to various studies conducted based on the classification of the mechanism of action, drugs such as analgesics and pain relievers [22], antipyretics, analgesics, antispasmodics, antibiotics, antacids, and vitamins [23], antibiotics and pain-spasm relievers [24], antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) [12], antibiotics and analgesics [2], NSAIDs, antibiotics, and vitamins [13], were reported. In studies conducted in Mexico and Saudi Arabia, which are located in two different geographies, NSAIDs came to the forefront [25, 26]. It is seen that the findings of studies based on the mechanism of action of unused pharmaceuticals in the literature are similar to each other. In our study, ATC classification was performed and it can be said that the Turkish context also supports the existing literature.

According to the findings of our study, 50.6% of the total number of dosage forms of pharmaceuticals were used but 49.4% were unused. Patients should follow the treatment procedure prescribed by the physician. However, in some cases, medication may be stopped early by the patient. Some studies have reported that the most important reason for having unused or expired pharmaceuticals in household is recovery [1, 27]. Other reported reasons were a change in treatment by the doctor and feeling well [28]. In our study, we showed that approximately half of the medicines were not used. The presence of unused medicines in households might be related to self-medication. In our study the prevalence of self-medication was 94.1%. Analgesics, common cold and muscle relaxants of the pharmaceuticals were found to be the most commonly used pharmaceuticals without consulting a physician. This finding was reported by Kumar et al. (2013) as 78.6% [29], by Niromand et al. (2020) as 72% [30], by Abdi et al. (2018) as 89.6% [31], and by Bahzadifar et al. (2020) as 70.1%. In the same study, it was reported as 97.2% in medical students and 44.7% in non-medical students [32]. According to the findings of a local study, the prevalence of self-medication was 64.3%, and it was found that analgesics, antibiotics and cold pharmaceuticals were mostly used in this way [33]. In another study, analgesics, antibiotics and antacid pharmaceuticals came to the forefront [34]. When we compare the findings of previous studies with our finding, it is possible to say that a finding similar to the literature has emerged when the number and quantity of unused pharmaceuticals at home are taken into consideration and that the prevalence related to self-medication is one of the highest findings in the literature.

Conclusion

According to findings, there is a significant quantity and number of unused pharmaceuticals with various active ingredients in households. It was observed that the unused pharmaceuticals were used without consulting a physician, were not disposed of properly, and some of them had expired. Considering the conditions associated with pharmaceuticals, this situation points to a significant public health problem for both people and environment. The public urgently needs to be informed about the use of pharmaceuticals. The accumulation resulting from any discontinuation of pharmaceutical therapy needs to be monitored and updated public health policies and legislation are required. In addition, a “drug take-back system” for unused pharmaceuticals may be useful in solving this problem.

Limits of the study

This study has some limitations. The limitations of this study included the fact that a significant portion of the study data was collected by online method, that it was based on the statements and practices of the participants, and that some pharmaceuticals might not be reported by the participants considering that they were related to privacy and research data were collected from a single center.