As e-commerce and online pharmacies (OPs) arose, the potential impact of the Internet on the world of health shifted from merely the spread of information to a real opportunity to acquire health services directly. Aim of the study was to investigate the offer of prescription drugs in OPs, analysing their characteristics, using the content analysis method. The research performed using the Google search engine led to an analysis of 118 online pharmacies. Only 51 (43.2%) of them stated their precise location. Ninety-six (81.4%) online pharmacies did not require a medical prescription from the customer's physician. Online pharmacies rise complex issues in terms of patient-doctor relationship, consumer empowerment, drug quality, regulation and public health implication

Caimi, Luigi

Domenighini, Serena

Gelatti, Umberto

Orizio, Grazia

Rosati, Cristina

Rubinelli, Sara

Schulz, Peter

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. . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . .. . . . . . . . . . . . . . .. . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . .Short Report. . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . .. . . . . . . . . . . . . . .. . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . .Cyberdrugs: a cross-sectional study of onlinepharmacies characteristicsGrazia Orizio1, Peter Schulz2, Serena Domenighini1, Luigi Caimi3,Cristina Rosati1, Sara Rubinelli2, Umberto Gelatti1As e-commerce and online pharmacies (OPs) arose, the potential impact of the Internet on the world ofhealth shifted from merely the spread of information to a real opportunity to acquire health servicesdirectly. Aim of the study was to investigate the offer of prescription drugs in OPs, analysing theircharacteristics, using the content analysis method. The research performed using the Google searchengine led to an analysis of 118 online pharmacies. Only 51 (43.2%) of them stated their preciselocation. Ninety-six (81.4%) online pharmacies did not require a medical prescription from thecustomer’s physician. Online pharmacies rise complex issues in terms of patient–doctor relationship,consumer empowerment, drug quality, regulation and public health implications.Keywords: internet, pharmaceutical preparations, public health.. . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . .. . . . . . . . . . . . . . . .. . . . . . . . . . . . . . .. . . . . . . . . . . . . . . .. . . . . . . . . . . . . . .IntroductionOnline pharmacies (OPs) are companies which sell drugs,including prescription-only drugs, through the Internet.This phenomenon started in the late nineties1 and has grownso much that the United States Food and Drug Administration(FDA) defines it as a ‘serious public health risk’, when itbecomes ‘the sale of unapproved drugs and the illegal saleof approved drugs over the Internet’.2 The World HealthOrganization (WHO) faces this issue in the context of coun-terfeit medicines, which are defined as ‘a global public healthcrisis’, stating that ‘medicines purchased over the Internetfrom sites that conceal their physical address are counterfeit inover 50% of cases’.3 In this context, it is very difficult toestimate the number of people buying online, the volumeof drugs traded and the economic extent of this business.4Anyway, the risk represented by a free market of prescriptiondrugs which transforms patients into consumers is clearlyexemplified by some clinical cases arising in association withmedication purchased via the Internet,5 and by surveys inwhich researchers successfully purchased prescription medica-tions by the internet.6 Until now, e-commerce of drugs doesnot yet seem to have spread much in Europe, but the Sentenceof the EU Court of Justice related to the ‘Doc Morris case’shows how living the matter can quickly become.1,7 In order toinvestigate the offer of online prescription drugs, we conducteda survey of OPs using a search engine and we analysed thecharacteristics of the websites found, focusing in particularon the geographical features of the companies, on theirprescription requirements and promotion strategies, on thekind of drugs offered and the declaration of side effects.MethodsThe search for OPs was conducted in August 2007 using theGoogle search engine and the entire web was searched using askeywords ‘online pharmacies’, ‘online drugstore’, ‘drugsonline’ and ‘medicines online’, according to the methodologyof previous OPs investigations.8 The first 30 references wereanalysed for each keyword. The inclusion language was atleast English, and the sampling frame comprised only OPsselling directly. The OPs websites were coded using an ad hocCodebook, according to the Content Analysis method,9 aboutaddress, extension, prescription requirements and sellingarguments. We investigated whether the OPs gave a detailedphysical location with a clear geographical reference or hadonly a virtual interface. We examined the offer of prescriptiondrugs, in particular of specific drugs with a high intrinsic riskof being dangerous or inappropriate: tramadol, alprazolam,amitriptyline, amphetamine or metamphetamine, codeineor hydrocodone, fluxetine, methylphenidate, phentermine,sidenafil, stanozolol, tramadol and valproic acid. An analysisof the declared side effects was conducted on the four mostfrequent drugs present in the OPs among the tracked oneslisted above. The data were analysed with STATA (StataStatistical Software Release 8.0, 2003; Stata Corporation,College Station, TX) using a descriptive approach andcalculating statistical significance using the 2 test, the Fisherexact test and the Mann–Whitney test, rejecting the nullhypothesis below a P-value of 0.05.ResultsWe found 118 websites fitting the inclusion criteria, of which51 (43.2%) with a specific address and 67 (56.8%) with avirtual interface only. The most frequent website extension was‘.com’, in 91 OPs (77.1%). Domains of registration weredistributed as follows in the world areas: 60 (50.9%) in theUnited States, 26 (22.0%) in Europe, 11 (9.3%) in Canada and15 (12.7%) in other countries; for six websites (5.0%) it wasnot possible to ascertain domain registration. Fifty-one(43.2%) of the OPs gave full details of the physical location:18 stated they were in the United States (35.3%), 18 in Europe(35.3%), 10 in Canada (19.6%) and five elsewhere (9.8%).Only in the 54.9% of OPs declaring their physical location, thelatter corresponded to the area of domain registration.Correspondence: Grazia Orizio, Sezione di Igiene Epidemiologia eSanita` Pubblica, Dipartimento di Medicina Sperimentale ed Applicata,Universita` degli Studi di Brescia, Viale Europa 11 - 25128 Brescia,Italy, tel: +39 030 3838611, fax: +39 030 3701404,e-mail: gorizio@med.unibs.it1 Section of Hygiene Epidemiology and Public Health, Department ofExperimental and Applied Medicine, University of Brescia, Italy2 Institute of Communication and Health, University of Lugano,Switzerland3 ‘Quality and Technology Assessment, Governance andCommunication Strategies in Health Systems’ Study and ResearchCentre, University of Brescia, ItalyEuropean Journal of Public Health, Vol. 19, No. 4, 375–377 The Author 2009. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.doi:10.1093/eurpub/ckn146 Advance Access published on 16 January 2009Forty-nine (41.5%) OPs declared the location of drug delivery,which was mostly Asia (23 OPs, 46.9%), followed by theUnited States (12 OPs, 24.5%). Agreement between declaredphysical location and delivery location was found in 31.4% ofOPs proving both details.Regarding prescription requirement, 22 (18.6%) OPs askedfor a medical prescription (prescription online pharmacies,POPs), made out by the consumer’s physician. The remaining96 OPs (81.4%) did not ask for a medical prescription(non-prescription online pharmacies, nPOPs); of these, 30(31.6%) did not ask for any kind of medical information,whereas 66 (68.8%) required the consumer to fill in a medicalquestionnaire. POPs declared their physical location moreoften (72.7%) compared with nPOPs (36.5%), with astatistically significant difference (Fisher exact test: p = 0.003).An analysis of the sales promotion strategies revealed thatthe most frequent were the safe use of personal data, shortdelivery times, high drug quality, and the suggestion to buymore to pay less. The selling argument regarding not having toundergo a doctor’s examination and avoiding costs, queuesand embarrassment was present in 72.9% of nPOPs. Wecompared the use of selling arguments in POPs and nPOPs,and we found more present in nPOPs than in POPs with astatistically significant difference the selling arguments aboutdiscreet packaging, the suggestion to buy more to pay less, andthe promotion of a affiliation policy; free shipping policy wasperformed more frequently in POPs (figure 1).When we investigated the drugs that we chose for trackingwideness of offering, on the 118 websites all of them wereavailable both in POPs and nPOPs; most frequently we foundsidenafil, fluoxetine, tramadol and amitriptyline.In about one-fourth of OPs, no side effects were declared forthe four most frequently sold tracked drugs. The number ofdeclared side effects was significantly higher in nPOPs than inPOPs for fluoxetine and amitriptyline and not significantly fortramadol, whereas the number of side effects for sidenafil wassignificantly lower in nPOPs than in POPs (Mann–Whitneytest).DiscussionThis results show that more than half of the OPs did notdeclared their physical location, and a great discordance wasdetected between domain of registration, compared withphysical and delivery location, when declared. More than80% of the OPs did not asked for a medical prescription, madeout by the consumer’s physician, in order to purchase drugs.Many selling arguments were used to promote drugs, includednon having to see a doctor in order to access drugs. One forthof OPs did not declared any side effect.There are no doubts that the Internet—through its world-wide network of computers allowing the global sharing ofinformation—has changed several aspects of our lives. In 1999,health information was already being reported as among thetop three reasons why people use the web.10 But the big issuewhich is arising now is that it is no longer merely a question ofinformation and knowledge: patients can now use the Internetto purchase health services directly, i.e. drugs, medical devicesand medical tests.About drugs, the chance to avoid prescription boundariescan be a potential disruptor at multiple levels, both at anindividual level, between doctor and patient, becoming aneasy way to overcome the health professional filter in orderto access drugs,11 and at a public health level, where nationalhealth services can be influenced by mixed accesses inregulated systems.1Besides, the characteristics of OPs could be associated withthe quality of the drugs and service. Indeed, there have beenreports of concern regarding the drugs storage and shippingconditions, fraudulent and dangerous practices.11As a final consideration, thinking about the reasons thatcould lead a European citizen to purchase drugs from OPs,it could be hypothesised that the opportunity to avoid doctorsand safeguard privacy are the main reasons, instead ofeconomic ones for people who live in a regulated drugsmarket where final drugs prices are negotiated.ConclusionIn conclusion, OPs are likely to become an important publichealth issue in the near future, as they are growing in volumeand controversy.12 The fairly strict controls on the sale of drugswhich health authorities have successfully implementedsince the late 1990s can now be avoided quite easily throughe-commerce, which takes place in a globalized world withvirtually no barriers, and legislation seems to be late inregulating this complex and dynamic issue.In our opinion, the problem should be studied andaddressed on different levels: from the regulation point ofview, by increasing control and facing the legal issues; from thepublic health point of view, by increasing awareness aboutthe risks associated with buying drugs on the Internet andreinforcing the trust-based relationship between patient andboth the Pharmacist and the General Practitioner.Acknowledgements‘Quality and Technology Assessment, Governance andCommunication Strategies in Health Systems’ Study andResearch Centre – University of Brescia (Italy).The results were previously presented as oral presentations at: Sixth Interdisciplinary Conference on Communication,Medicine and Ethics ‘COMET 2008’ – Cape Town,South Africa 2–4 July 2008.g A content analysis of websites offering prescription-only drugs; Orizio G, Schulz P, Domenighini S,Rosati C, Rubinelli S, Caimi L, Gelatti U. 43 Congresso Nazionale SItI ‘La promozione dellasalute per lo sviluppo sociale ed economico dell’Italia: ilcontributo dell’Igiene e della Sanita` Pubblica’ – Bari 1-4Ottobre 2008.g La vendita dei farmaci in internet: implicazioni intermini di salute pubblica; Orizio G, Schulz P,Domenighini S, Rosati C, Rubinelli S, Donato F,Caimi L, Gelatti U.Conflicts of interest: None declared.20 40 60 80 100 118* p < 0.05*****Selling ArgumentsWe safe guard your private dataYour drugs arrive in a discreet packageThe more you buy the less you payLow pricesAffiliation policyFree shippingAdvice to buy another drug together with the selected oneShort delivery timesPossibility of checking order onlinePresence of testimonialsGood drug qualityBuying drugs online is legalYou don’t need to go to the doctorNo Prescription OPs Prescription OPsNumber of OPs0Figure 1 Number of selling arguments present on the sampleframe of the 118 online pharmacies376 European Journal of Public HealthKey points A cross-sectional study was performed on websitesselling drugs, analysing 118 online pharmacies, and wefound that the majority of them did not ask for amedical prescription, made out by the consumer’sphysician, in order to purchase prescription drugs. Numerous selling arguments were present to promotedrugs selling, in particular about the chance topurchase prescription medications without prescrip-tion and avoiding to see a doctor. Direct access to drugs through the internet risescomplex issues in terms of patient–doctor andpatient–pharmacist relationship, drug quality, healthpolicy, still to be faced both at a national and at aninternational level.References1 Makinen MM, Rautava PT, Forsstrom JJ. Do OPs fit European internalmarkets? Health Policy 2005;72:245–52.2 FDA, Food and Drugs Administration. Frequently asked questions, 2007.http://www.fda.gov/oc/buyonline/faqs.html (10 September 2007, dateaccessed).3 WHO, Fact sheet no 275, revised 14 November 2006. http://www.who.int/mediacentre/factsheets/fs275/en/index.html. (10 September 2007, dateaccessed).4 Fox S. Prescription drugs online. Pew internet and American life project.2004. www.pewinternet.org. (10 September 2007, date accessed).5 Lineberry TW, Bostwick JM. Taking the physician out of ‘physicianshopping’: a case series of clinical problems associated with internetpurchases of medication. Mayo Clin Proc 2004;79:1031–4.6 Gernburd P, Jadad AR. Will spam overwhelm our defenses? Evaluatingofferings for drugs and natural health products? PLoS Med 2007;4:e274.7 EU Court of Justice judgement of 11/12/2003, case C-322/1 DeutscherApothekerverband versus 0800 Doc Morris NV. http://eur-lex.europa.eu(10 September 2007, date accessed).8 Bessel TL, Silagy CA, Anderson JN, et al. Quality of global e-pharmacies: canwe safeguard consumers? Eur J Clin Pharmacol 2002;58:567–72.9 Riffe D, Lacy S, Fico FG. Analyzing media messages. Using quantitativecontent analysis in research. Mahwah, New Jersey: Lawrence Erlbaum, 2005.10 Cochrane JD. Healthcare at the speed of thought. Integr Healthc Rep1999;1–14, 16–7.11 Weiss AM. Buying prescription drugs on the Internet: promises and pitfalls.Cleve Clin J Med 2006;73:282–8.12 Bostwick JM, Lineberry TW. Do cheap internet drugs threaten the safety ofthe doctor-patient relationship? Expert Opin Drug Saf 2007;6:9–13.Received 27 October 2008, accepted 22 December 2008Drugs on the web 377

Cyberdrugs: a cross-sectional study of online pharmacies characteristics

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