Cost of generic sildenafil

The ideal study for preference evaluation should: (i) be randomized, double?blind, crossover; (ii) not include bias by pre?selection of patients (e.g. only nonresponders to previous treatment); (iii) make fair comparisons, adopting equivalent doses of each drug and giving each drug for equal periods; (iv) be based on an intent?to?treat analysis. He also indicated several pitfalls: drug instructions might differ considerably, e.g. because of differences in duration of action, and invalidate the blinding, or might even condition patient preference; period effects might produce improvements over time that bias results in studies with medications that require an adaptation period cost of generic sildenafil or training; carry?over effects might produce an overlap in the effects of medications, jeopardizing their comparison, when the wash?out interval between periods is too short.

He also raised the issue of how patient preference should be assessed. A single question, such as ‘Which treatment did you prefer?’ is limited, as it does provides no context to the answer. A multi?question preference questionnaire, including questions that are related to putative contributing factors, such as time to onset of action, duration of action, quality of erection and side?effects, is preferable. Several published studies are available that evaluated patient preference for tadalafil or vardenafil vs sildenafil teva 100mg price sildenafil and that meet some, but not all, the requirements listed above.

The aim of this review is to establish whether current knowledge enables any conclusive judgement.

We electronically searched Medline (from 1966 to 2007 week 18) and EMBASE (from 1988 to 2007 week 18) using the search string ‘(tadalafil or vardenafil) AND Sildenafil AND clinical trial AND erectile dysfunction’ combined with ‘drug preference OR drug choice OR patient preference OR patient attitude OR patient satisfaction’ and limited to articles in English and referring to humans.

The studies identified were stringently assessed according to the Mulhall criteria.

We identified seven patient?preference studies (Table 1) [ 5-12 ], comprising six interventional trials [ 5-10, 12 ] and one observational trial [ 11 ].

All of them compared tadalafil with sildenafil, except two, i.e. a large double?blind study by Rubio?Aurioles et al. [ 10 ] that compared vardenafil with sildenafil, and a small open?label study by Tolra et al. [ 9 ] that compared sildenafil with vardenafil and tadalafil. Three of the studies were declared as sponsored by Lilly ICOS LLC [ 7, 8, 11 ] and one jointly by Bayer and Glaxo?SmithKline [ 10 ].

Ref Design Population, n inclusion criteria Treatment Questionnaires [ 5 ] Randomized, double?blind Crossover Fixed dose 1–2 week washout SIL vs TAD 191 completers 18–65 years ?3 months ED Heterosexual TAD naive SIL naive/insufficient therapy SIL 50 mg 30 min up to 4 h before sex TAD 20 mg 30 min up to 24 h before sex ?4 weeks TP question SEP diary TEAE [ 6 ] Open?label, fixed cost of generic sildenafil dose, 1?way cross over, 1?week screening3?week SIL assess 1 week treatment?free washout 6?week TAD initiation 3?week TAD assess 6?month extension 147 completers ?18 years ?3?month history of ED on SIL treatment at stable dose for 6–24 weeks Stable heterosexual relationship SIL continue 25–100 mg as before (100 mg max 35%) TAD 20 mg % choosing TAD for

extension

DIP

Three of the five interventional studies [ 6, 8, 9 ] were open?label studies because of the difficulty in conducting a blind study with these compounds, as there are major differences in their instructions on cost of generic sildenafil use.

[ 5 ] is reduced by several other shortcomings; it included patients who were not naive to PDE5 inhibitor use, and the comparison of the two compounds was unfair, as tadalafil was given at its regular dose, whereas only the starting dose of sildenafil (50 mg) was given to patients, without the option of titrating to the maximum dose of 100 mg; moreover, the duration of treatment was too short (4 weeks).

Thus, the two pivotal patient?preference studies are the double?blind studies by Keitz et al. [ 7 ], which compared tadalafil and sildenafil, and by Rubio?Aurioles et al. In these two studies elaborate measures were taken that put patients in conditions that differed considerably from usual clinical practice. [ 5 ] had an elaborate crossover design; patients were randomized to one of 4 arms (i) tadalafil + tadalafil instructions vs sildenafil + sildenafil instructions; (ii) sildenafil + sildenafil instructions vs tadalafil + tadalafil instructions; (iii) tadalafil + tadalafil instructions vs tadalafil + sildenafil instructions; (iv) tadalafil + sildenafil instructions vs tadalafil + tadalafil instructions. The comparison between arm 1 and 2 was between drugs, whereas the comparison between arm 3 and 4 was between instructions. This design enabled the study to also address the key issue of the difference in instruction sets by comparing these while always giving the same drug, tadalafil. The only pitfall of this study is that 66% of the patients were not naive to PDE5 inhibitor. Double?blind conditions were achieved in the study by Rubio?Aurioles et al. [ 10 ] by encapsulating sildenafil tablets, creating a formulation that does not exist on the market. This obliged them to carry out another trial to show the bioequivalence of the encapsulated formulation with the marketed one.

This appears to be the only flaw of the study, which met all the main Mulhall criteria for patient?preference studies.

However, the patient population only included a particular subgroup of PDE5 inhibitor users, those with cardiovascular risk factors, i.e. diabetes mellitus, hypertension and/or hyperlipidaemia [ 10 ], Particular populations were recruited also in the other studies by [ 6, 8, 9, 11 ], which are also important, notwithstanding the lack of blinding, for this very reason. Their patient populations included: all patients naive to PDE5 inhibitor [ 8, 9 ], the general population including the elderly [ 6, 8, 9 ], patients in a non?interventional clinical practice setting [ 11 ], different cultural settings in terms of country (USA/Canada and various European countries, including UK, Sweden, Italy, Spain, Germany) and different healthcare settings (general hospitals, University teaching hospitals, private practice). A non?interventional setting that closely resembled routine clinical practice is the main strength of the large observational study by Lee et al.

This study enrolled 2425 patients in Canada, and assessed some of the partners, using more detailed questionnaires, which provide more extensive information related to the reasons for preference: the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), the Psychological and Interpersonal Relationship Scale (PAIRS), the Drug Attribute Questionnaire, and preference questions put not only to the patient but also to the partner. Such questionnaires were also used in the studies by Eardley et al. All the studies comparing tadalafil and sildenafil showed a significant preference for tadalafil than sildenafil (Table 2). [ 7 ] was clear; 73% of patients preferred tadalafil to sildenafil ( P 9 ] to 90.5% in the study by Stroberg et al. However, the latter trial was conducted in patients who had taken sildenafil for 5, 8, 9, 11 ] was much more similar to the study of von Keitz et al. [ 7 ], as the proportion of patients who preferred tadalafil was 66–71%. [ 9 ] vardenafil was the least popular PDE5 inhibitor, as only 20% of patients preferred this drug.

However, the sample was too small to provide adequate power, so this preference rate should be considered as a preliminary finding. Its results were contradicted by the large, adequately powered, non?inferiority, double?blind study by Rubio?Aurioles et al.

[ 10 ], which documented a 38.9% preference rate for vardenafil vs 34.5% for sildenafil (26.6% of patients had no preference).

Some studies also addressed secondary preference objectives. [ 8 ], in which patients were asked to specify whether they preferred one drug to the other ‘strongly’ or ‘moderately’, 73% of the patients who preferred tadalafil had a strong preference, vs only 45% amongst those who preferred sildenafil.