AFT Pharmaceuticals (AU) Pty Ltd v Reckitt Benckiser [2020] FCA 672 | Case summary

AFT Pharmaceuticals (AU) Pty Ltd v Reckitt Benckiser [2020] FCA 672 | Case summary | Zoe

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Introduction 1 The applicant (AFT) seeks a declaration that there is an adequate scientific foundation for statements which appear in an advertisement for its analgesic product, marketed and sold in Australia, called "Maxigesic" (new advertisement). Maxigesic is an ibuprofen/paracetamol combination medicine, which contains 150mg of ibuprofen and 500mg of paracetamol in a single tablet. 2 In summary, the advertisement makes claims to the effect that Maxigesic provides "better and faster" pain relief than paracetamol or ibuprofen alone. AFT contends that a 2018 study published in Daniels et al., "Analgesic Efficacy of an Acetaminophen/Ibuprofen Fixed-dose Combination in Moderate to Severe Postoperative Dental Pain: A Randomized, Double-blind, Parallel-group, Placebo-controlled Trial" (2018) 40(10) Clinical Therapeutics 1765 (Daniels 2018 study), and a substantial body of scientific evidence consistent with the Daniels 2018 study, provide the scientific foundation for its claims. 3 The proceeding was commenced in February 2019, after a finding that AFT contravened the Australian Consumer Law, being Sch 2 to the Competition and Consumer Act 2010 (Cth), by publishing other different advertisements for Maxigesic: Reckitt Benckiser (Australia) Pty Limited v AFT Pharmaceuticals (AU) Pty Limited [2018] FCA 1552 (2018 judgment); decision upheld on appeal: AFT Pharmaceuticals (AU) Pty Limited v Reckitt Benckiser (Australia) Pty Limited [2020] FCAFC 45 (appeal judgment). The 2018 judgment was based on a conclusion that representations contained in those other advertisements lacked an adequate scientific foundation. 4 The 2018 judgment did not consider the Daniels 2018 study. 5 The 2018 judgment addressed claims which compared Maxigesic with paracetamol and ibuprofen as monotherapies (that is, in a product containing a single active ingredient, an example of which is an ibuprofen product marketed and sold by the respondent/cross-claimant (Reckitt) under the name "Nurofen"), as well as claims which compared Maxigesic with other combinations of paracetamol and ibuprofen (and, specifically, "Nuromol", another product marketed and sold by Reckitt). 6 The 2018 judgment principally concerned representations directed to comparative performance of the relevant drugs when taken at their respective maximum daily doses. The representations involving a comparison of Maxigesic with paracetamol and ibuprofen as monotherapies were: (1) when taken at their respective maximum recommended daily doses, Maxigesic provides stronger and more effective relief from pain than over the counter (OTC) doses of either paracetamol or ibuprofen alone (representation (3) in the 2018 judgment); and (2) Maxigesic reduces pain by at least 32% more than a full daily OTC dose of either paracetamol or ibuprofen alone throughout the period of administration of either drug (representation (4) in the 2018 judgment). 7 By order 12 of orders made on 29 November 2018, the Court imposed a permanent injunction on AFT restraining it from making the representation (among others) that, when taken at their respective maximum recommended daily doses, Maxigesic provides stronger and more effective relief from pain than OTC doses of either paracetamol or ibuprofen alone without an adequate scientific foundation for doing so (restrained representation). 8 Reckitt disputes AFT's entitlement to the declaration sought on the basis that the claims made in the new advertisement do not have an adequate scientific foundation. Further, by its cross-claim, Reckitt alleges that the new advertisement conveys the restrained representation. Reckitt also contends that the new advertisement, and other advertising materials making similar representations, contravene the Australian Consumer Law because those representations lack an adequate scientific foundation. 9 Accordingly, the principal issue for determination is whether or not there is an adequate scientific foundation for the claims now made and the representations conveyed by AFT's advertising materials.

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Footnote 13 AFT pleads that the reference denoted by "1" in both the new advertisement and the training aid reads as follows: (a) (in the middle of the page) "Daniels study results assessed on the intent-to-treat (ITT) population with adjustment for the use of rescue medication. Sensitivity analysis confirms primary endpoint independent of rescue medication adjustment1." (mid-page footnote); and (b) (at the foot of the page) "References: Daniels SE, Atkinson HC, Stanescu I, and Frampton C (2018), "Analgesic Efficacy of an Acetaminophen/Ibuprofen Fixed dose Combination in Moderate to Severe Postoperative Dental Pain: A Randomized, Double-blind, Parallel-group, Placebo-controlled Trial", Clinical Therapeutics 40 (10): 1765 - 1776. Result achieved in a trial of post-operative pain relief after removal of at least 2 impacted third molars using Maxigesic® fixed-dose combination (Paracetamol 975mg/Ibuprofen 292.5mg) compared with Paracetamol 975mg or Ibuprofen 292.5mg alone 4 times a day (Paracetamol 3900mg or Ibuprofen 1170mg per day). Maxigesic® 975/292.5mg combination is bioequivalent to Maxigesic® 1000/300mg Australian combination at full dose (Aitken et al, J Bioequiv Availab, 10:5). Research sponsored by AFT Pharmaceuticals…" (bottom page footnote) 14 For its part, Reckitt admits that the text set out above appears in "very small" font on the face of the new advertisement; and says that the text is so small of itself and/or by comparison to the surrounding text and/or is placed in such a position on the advertisement that it would not be read by a casual or reasonable observer of the advertisement and/or otherwise would not and does not operate to qualify the statements to which the reference denoted by "1" is affixed in the advertisement. 15 The font of the mid-page footnote is not so small as to be unreadable. The use of the reference denoted by "1" in connection with the descriptors "better", "faster" and "superior" draws attention to the mid-page footnote. A reasonable reader of the new advertisement would be likely to read out the mid-page footnote when considering the footnoted statements in the advertisement. 16 The font of the bottom page footnote is smaller. AFT submitted that the Court should approach the matter on the basis that some readers, likely the majority, would not read the footnotes (although some would read the footnotes). On that basis, I have considered the meaning of the new advertisement on the footing that the information in the footnotes would not necessarily form part of the context in which statements in the new advertisement are to be understood. 17 For those readers who would read the footnotes, AFT noted that the footnotes to all of the advertising materials contain: (a) a statement that in the Daniels 2018 study, the participants took the fixed dose combination medicine four times a day; (b) a statement based on the Aitken Study that a fixed dose combination of 975mg of paracetamol and 292.5mg of ibuprofen (Daniels FDC) is bioequivalent to a fixed dose combination of 1000mg of paracetamol and 300mg of ibuprofen (i.e. Maxigesic) at full dose; and (c) in the context of product safety, a direction not to exceed the daily recommended dose. 18 However, AFT submitted the footnoted content was of "little relevance to the identification of the representations conveyed", observing that the statements which convey the disputed representations are not found in the footnotes, but rather in the body of the various advertising materials.

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Legal framework 24 The relevant legal framework is set out in the 2018 judgment at [18] to [41], including the relevant provisions of the Australian Consumer Law and principles as to what is an adequate foundation for claims of a scientific nature. Of particular relevance is the following statement in Reckitt Benckiser (Australia) Pty Ltd v GlaxoSmithKline Australia Pty Ltd [2018] FCAFC 138 (GSK) at [41]: When evaluating whether there was an adequate foundation in the body of scientific knowledge to support the representations that were made, the primary judge did not err by taking into account the totality of the scientific evidence available at the relevant time. Further, the primary judge did not err by concluding that it would be misleading or deceptive, or likely to mislead or deceive, to make the impugned representations on the basis of the Schachtel Study alone, when the balance of the scientific evidence demonstrated no clear-cut superiority of ibuprofen over paracetamol in terms of faster and more effective relief from pain caused by common headaches including [tension-type headaches]. The body of scientific evidence, which took into account the findings of the Schachtel Study, but balanced them against the findings of other studies, did not support the making of simplistic comparisons of the kind found in Reckitt's comparative advertising material. It was misleading for Reckitt to make the representations it did-which carried with them an unqualified and definitive statement of scientific fact-when the overall conclusion to be drawn from the scientific evidence was that no authoritative comparisons between active treatments were possible in the then state of scientific knowledge. 25 AFT argues that in GSK, the Schachtel study (referred to in the passage above) was an outlier, in contrast to its case where, AFT contends, the Daniels 2018 study is consistent with a substantial body of scientific evidence. 26 In the appeal from the 2018 judgment, AFT accepted that the legal principles had been correctly stated but argued that they had been misapplied. In the appeal judgment, the Full Court summarised the case that Reckitt was required to make, on the basis of those principles, as follows (at [8]): Reckitt bore the onus of establishing that there was no adequate scientific foundation for the impugned representations and thus that they were misleading or likely to mislead. That did not require Reckitt to positively establish that, at their respective recommended daily doses, Maxigesic does not provide stronger and more effective relief from all pain than Nuromol and other OTC paracetamol/ibuprofen combinations. It was enough for Reckitt to establish that, taking into account the totality of the scientific evidence available at the relevant time, which included evidence going both ways, the balance of the scientific evidence did not provide an adequate scientific foundation for AFT's simplistic representation that Maxigesic provides stronger and more effective relief from all pain than Nuromol and other OTC paracetamol/ibuprofen combinations, carrying as it did a representation that was an unqualified statement of scientific fact.

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How advertising material should be interpreted 27 Reckitt made the following submissions, which were not contentious: (1) When considering whether advertising is misleading or deceptive, or likely to mislead of deceive, "the 'dominant message' of the material will be of crucial importance": Australian Competition and Consumer Commission v Coles Supermarkets Australia Pty Ltd [2014] FCA 634 (ACCC v Coles) at [42], citing Australian Competition and Consumer Commission v TPG Internet Pty Ltd [2013] HCA 54; (2013) 250 CLR 640 (TPG) at [45]. In ACCC v Coles at [160], Allsop CJ stated: … the courts should be astute and careful not to permit consumers to be misled on available meanings or connotations of phrases deliberately chosen to sell products on the basis that everyone takes advertising with a pinch of salt. To place emphasis on advertising licence that bends the truth will not only degrade the language, but lead to a culture of deception in the market. These matters do not elevate this case to a question of principle, but they should be borne in mind when broad laudatory language, intended to affect the buying decisions of members of the public, is such as to lead consumers into error and so to mislead or deceive, and the justification for such involves an intellectual shrug and a knowing nod to the effect that the public is cynical enough to look after itself… (2) While "[t]here may be occasions upon which the effect of otherwise misleading or deceptive conduct may be neutralised by an appropriate disclaimer", the general rule is that "a person engaging in misleading or deceptive conduct cannot use the device of a disclaimer to evade responsibility, unless that disclaimer erases the proscribed effect": iNova Pharmaceuticals (Australia) Pty Ltd v Reckitt Benckiser (Australia) Pty Ltd [2018] FCA 1209 at [25(1)]-[25(2)]. See also Australian Competition and Consumer Commission v Signature Security Group Pty Ltd [2003] FCA 3 at [26] and [27]; Medical Benefits Fund of Australia Ltd v Cassidy (2003) 135 FCR 1 at [37] ff and National Exchange Pty Ltd v Australian Securities and Investments Commission [2004] FCAFC 90 at [50], [51] and [55]. (3) In assessing whether "qualifying" or "additional" material is sufficiently prominent or conspicuous, "it is appropriate to consider not simply the words or images depicted but also their relative emphasis (whether by print size, location, colour or other manner of presentation)": Australian Competition and Consumer Commission v Harris Scarfe Australia Pty Ltd [2009] FCA 54 at [53]. Important matters will include "the way the asterisk is placed, the size of the footnote relative to the text in the body of the advertisement, and the terms of the footnote": ibid, citing Trade Practices Commission v QDSV Holdings Pty Ltd (t/as Bush Friends Australia) [1994] FCA 1562 at [37]-[40]. (4) As pointed out by Hill J in Tobacco Institute of Australia Ltd v Australian Federation of Consumer Organisations Inc [1992] FCA 630; (1992) 38 FCR 1 at 50: Where… the advertisement is capable of more than one meaning, the question of whether the conduct of placing the advertisement in a newspaper is misleading or deceptive conduct must be tested against each meaning which is reasonably open. This is perhaps but another way of saying that the advertisement will be misleading or likely to mislead or deceive if any reasonable interpretation of it would lead a member of the class, who can be expected to read it, into error. …

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Res judicata/Issue estoppel 28 Reckitt contended that the 2018 judgment considered "the body of scientific evidence in the context of the alleged superiority of Maxigesic over the monotherapies and found that it did not support the claims made." Reckitt submitted that AFT was bound by that finding and precluded from re-opening that question by the operation of the doctrine of res judicata and or issue estoppel. 29 I do not accept the premise of this argument because it mis-states the case that was determined in the earlier proceeding. Relevantly, that case was not simply the alleged superiority of Maxigesic over the monotherapies, but the narrower issue of whether there was an adequate scientific foundation for the restrained representation, which concerned the superiority of Maxigesic over the monotherapies "when taken at their respective maximum recommended daily doses". 30 In contrast, as appears below, and although Reckitt does contend that the restrained representation is made by the advertising materials now in issue, AFT is bringing a case about claims that are different from the restrained representation. In turn, Reckitt's cross-claim pleads representations apart from the restrained representation. For example, the agreed representation, that Maxigesic is more efficacious than paracetamol or ibuprofen alone, is broader than the restrained representation in that it is not confined by any dose or dosage period. 31 The concepts of res judicata and issue estoppel were explained by the High Court in Tomlinson v Ramsey Food Processing Pty Ltd [2015] HCA 28; (2015) 256 CLR 507 (Tomlinson) at [20]-[23]. 32 In summary, the doctrine of res judicata provides that where judgment has been entered on a cause of action, no proceeding can thereafter be maintained on the same cause of action: Jackson v Goldsmith [1950] HCA 22; (1950) 81 CLR 446 at 466. The doctrine requires focus on the substance of the two proceedings: Trawl Industries of Australia Pty Ltd v Effem Food Pty Ltd [1992] FCA 272 at [51], [53]; that is, whether the controversy in the proceeding was determined in the first proceeding: Re Twenty-First Larena Pty Ltd; Maximova v Goodwin & Ors [2010] VSC 84 at [23]. 33 In this case, having been unsuccessful in the 2018 judgment, AFT now seeks to argue that there is an adequate scientific foundation for claims made in a new and different advertisement that had not been published at the time of the 2018 judgment. AFT also seeks to argue that there is an adequate scientific foundation for new and different representations upon which Reckitt founds new claims for relief. 34 This proceeding can be characterised as a further iteration of a single controversy between AFT and Reckitt about whether AFT has an adequate scientific basis for its advertising of Maxigesic. However, once it is accepted that AFT's disputed advertising materials contain materially different claims and representations, it is impossible to conclude that the 2018 judgment disposed of the issues raised by those materials or that the current proceeding involves a re-litigation of the earlier proceeding. In that sense, this proceeding concerns a new controversy. 35 Accordingly, AFT is not now seeking to rely on a cause of action that has merged in the 2018 judgment and is not precluded by the doctrine of res judicata from either bringing its primary claim or defending Reckitt's cross-claim by reason of the earlier judgment. 36 Issue estoppel operates to preclude the raising in a subsequent proceeding of an ultimate issue of fact or law which was necessarily resolved as a step in reaching the determination made in an earlier judgment (Tomlinson at [22]). In Blair v Curran [1939] HCA 23; (1939) 62 CLR 464 at 532, Dixon J explained: The distinction between res judicata and issue estoppel is that in the first the very right or cause of action claimed or put in suit has in the former proceedings passed into judgment, so that it is merged and has no longer an independent existence, while in the second, for the purpose of some other claim or cause of action, a state of fact or law is alleged or denied the existence of which is a matter necessarily decided by the prior judgment, decree or order. Nothing but what is legally indispensable to the conclusion is thus finally closed or precluded. In matters of fact the issue estoppel is confined to those ultimate facts which form the ingredients in the cause of action, that is, the title to the right established. 37 The 2018 judgment resolved the factual issue of whether there was an adequate scientific foundation for, relevantly, the restrained representation. It did not resolve, for example, the factual question whether there is an adequate scientific foundation for the representation that Maxigesic is more efficacious than paracetamol or ibuprofen alone. Nor did it resolve the factual issue of whether there is now an adequate scientific foundation for the restrained representation because the science has evolved and, specifically, now includes the Daniels 2018 study. 38 In particular, I do not accept Reckitt's argument that all of the representations the subject of this proceeding are relevantly identical to the restrained representation. If that were the case, Reckitt's cross-claim would lack utility to the extent that it pleads other representations, to say the least. However, I do not consider that Reckitt's cross-claim lacks utility because I accept that it pleads new causes of action based on new and different representations.

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Restrained representation 46 Reckitt contended that the advertising material uses the same language as provided a basis for the finding that the restrained representation was made in the 2018 judgment (namely "GET BETTER PAIN RELIEF than Paracetamol or Ibuprofen alone": see 2018 judgment at [85]). Reckitt noted that the words "and faster" are interposed between "better" and "pain relief" in the new advertisement and the training aid, but submitted that this makes no difference of substance. 47 It was not clear whether AFT disputed that a reasonable reader could understand the advertising materials to make a comparison between the relevant drugs "when taken at their respective maximum recommended daily doses". 48 In my view, at least a reasonable reader who was able to read the bottom page footnote could understand the materials in that way because of the description of the trial dosages on a daily basis (that is "Maxigesic® fixed-dose combination (Paracetamol 975mg/Ibuprofen 292.5mg) compared with Paracetamol 975mg or Ibuprofen 292.5mg alone 4 times a day (Paracetamol 3900mg or Ibuprofen 1170mg per day)". 49 Further, Professor Anthony Keech, an expert in relation to the conduct of clinical trials, gave uncontested evidence on behalf of Reckitt that the packaging of Maxigesic refers to dosage over a 24 hour period only. Dr Marc Russo, a specialist pain medicine physician who gave evidence on behalf of AFT, also said that there is "one concept of [sic] Maxigesic can be taken as a maximum of two tablets every six hours, not exceeding eight in a 24-hour period". Accepting that at least some readers of the advertisement are likely to be familiar with the packaging or the concept described by Dr Russo, that provides another basis for a reasonable reader to understand the words "at maximum dosage" to refer to the maximum recommended daily doses. 50 In saying this, I note that Dr Russo's evidence was that a reasonable pharmacist would not understand that the asserted benefits of Maxigesic would apply after taking the drug at its maximum dosage for 24 hours. Dr Russo said that such a reader would necessarily conclude that the maximum dosage would be related to the time periods specified in the study, because it is obvious from the advertising materials that they are to be understood in the context of the Daniels 2018 study. 51 Although I generally found Dr Russo to be a very impressive witness, I do not accept his evidence on this point which goes beyond his expertise as a pain physician. As his evidence revealed, maximum dosage of Maxigesic is generally measured on a six hourly basis and a daily basis. By not being more specific, AFT left it open to a reasonable reader of the relevant class of readers (noting that this class varies as between the different advertising materials) to conclude that "maximum dosage" referred to the maximum recommended doses. 52 AFT noted that, in contrast with the promotional materials addressed by the 2018 judgment, the word "stronger" is not used in the advertising materials under consideration in this proceeding. AFT submitted that the 2018 judgment was made on evidence that included evidence about the meaning of the word "stronger" in the context of the relevant promotional materials, and that no such evidence was adduced in this proceeding. 53 In my view, a reasonable interpretation of each of the advertising materials includes a claim in the terms of the restrained representation. In the cases of the new advertisement and the training aids, the interpretation arises from the references to "better" pain relief, "superior analgesic efficacy" and "more effective pain relief" because "stronger … pain relief" is one of the things that a reasonable reader might think would be entailed in those claims, since pain can be experienced in degrees of severity that might be thought to be alleviated by "stronger" pain relief. In the case of the POS materials, the interpretation arises from the reference to "better pain relief".

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Daniels 2018 study 60 The Daniels 2018 study was a clinical trial which compared: (a) a fixed dose combination of 975mg paracetamol/ 292.5mg ibuprofen (comprising three tablets) (that is, the Daniels FDC); (b) paracetamol; (c) ibuprofen; and (d) placebo. 61 The study publication concludes (at p 1774) that the Daniels FDC: ...provided significantly superior analgesia over equivalent monotherapy doses of either ingredient alone in the treatment of moderate to severe pain in the 48 hour period after the extraction of at least 2 impacted third molars. Compared with both monotherapies and placebo, the fixed-dose combination provided a significantly shorter onset of meaningful pain relief, reduced the consumption of opioid rescue medication, and reduced maximum pain scores... 62 Under the heading "Discussion", the study publication states: Acetaminophen and ibuprofen are well-known, commonly used, and well-established analgesic agents for the treatment of mild to moderate pain, and they target pain through separate pathways. The present study adds to the existing literature that shows the additive analgesic effect of combined acetaminophen and ibuprofen over either monotherapy after third molar removal, over ibuprofen monotherapy after root canal, and over acetaminophen monotherapy in other pain models. Several of pain studies in emergency department patients have not shown the superiority of combined therapy over monotherapy, possibly due to differences in study populations, baseline pain levels, indications, study duration, and dosing regiments. This study is the first to show the superiority of a fixed-dose combination that provides doses of both active ingredients at the recommended OTC levels and adheres to the FDA [US Food and Drug Administration] request for the dose of acetaminophen to be limited to 325mg per unit. This study reinforces previous research by showing that when co-administered, acetaminophen and ibuprofen combine to deliver a superior analgesic effect over either active ingredient alone. This study reinforces previous research by showing that when co-administered, acetaminophen and ibuprofen combine to deliver a superior analgesic effect over either active ingredient alone. With comparisons versus equivalent doses of each drug, it is evident that both active ingredients contribute to the superior analgesic effect of the fixed-dose combination. 63 The study publication also states: "The findings of the present study are limited to adults and to a dental pain model." 64 As appears from the study publication conclusion set out above, the primary end point of the Daniels 2018 study was the time-adjusted sum of pain intensity difference over 48 hours (SPID48). The authors of the Daniels 2018 study concluded (at p 1768) that analysis of the time-adjusted SPID48 "... showed that [Daniels] FDC 975/292.5 provided more effective pain relief than placebo, acetaminophen or ibuprofen". 65 The abstract of the study publication sets out the following implications of the study: Overall, the fixed-dose combination of acetaminophen and ibuprofen provided greater and more rapid analgesia than comparable doses of either agent alone or placebo in adults after removal of impacted third molars. 66 AFT also contended that it was important to note the post hoc additional analysis showing that over the first six hours of treatment (that, is, during the first dosing period), the Daniels 2018 study found that the SPID6 was 151% greater for Daniels FDC 975/292.5 than for paracetamol monotherapy (25.61 vs 10.20) and was 52% greater for FDC 975/292.5 than for ibuprofen monotherapy (25.61 vs 16.82) (at p 1771). In each case, these improvements were statistically significant. 67 The Daniels 2018 study also analysed several pre-determined secondary end points. The study publication identified the secondary end points as follows: Secondary end points of the study included the following: time to perceptible and meaningful pain relief using the two-stopwatch method; maximum VAS [visual analogue scale] pain intensity score after the first dose of study medication; percentage of patients requiring rescue medication, time to first doses of rescue medication, and cumulative consumption (milligrams) of rescue medication; percentage of patients that achieved 50% maximum pain relief over six hours post-surgery, than those receiving 400mg ibuprofen or 1000mg paracetamol". That finding is not recorded on p 21 of the study publication. 147 Reckitt noted the following matters concerning the review: (1) The review analysed the "proportion of patients with at least 50% pain relief (based on total pain relief (TOTPAR) and summed pain intensity difference (SPID) data) … at both two and six hours postdosing". (2) Insofar as the combination analgesic was concerned, the review analysed the results of only one study: the Mehlisch No. 1 Study, as Dr Russo agreed in cross-examination. (3) Concerning the quality of the evidence review, the Bailey review notes that "when comparing the combined versus single drugs, the body of evidence for the proportion of patients with >50% maximum pain relief ... over two and six hours was assessed as of moderate quality due to imprecise estimates based on single studies. This means that further research is likely to have an important impact on our confidence in the estimate of the effect". (4) One of the stated "key results" was that "[o]n limited evidence, the combination of ibuprofen and paracetamol appeared to be no more effective than the single drugs when measured two hours after surgery. However, again on limited evidence, it was found to be more effective than the drugs taken singly when measured at six hours after surgery. Participants taking the combined drug also had a smaller chance of requiring rescue medication". (5) The review did not analyse time to onset of pain relief.

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Derry review (2013) 148 The Derry review, entitled "Single dose oral ibuprofen plus paracetamol (acetaminophen) for acute postoperative pain (Review)" was a Cochrane review of the three studies addressed below: the Daniels 2011 study, the Mehlisch No. 1 study and the Mehlisch No. 2 study. The review assessed the efficacy and safety of a single dose of a paracetamol/ibuprofen combination analgesic (with varying amounts of paracetamol and ibuprofen) as against either the same amount of ibuprofen or placebo. 149 The authors concluded (at p 2): Ibuprofen plus paracetamol combinations provided better analgesia than either drug alone (at the same dose), with a smaller chance of needing additional analgesia over about eight hours, and with a smaller chance of experiencing an adverse event. 150 Dr Russo stated that the following findings of this review are particularly relevant: (1) 1000 mg paracetamol/400 mg ibuprofen provided better pain relief over six hours than 400mg ibuprofen with the combination giving an NNT of 1.6 (1.5 to 1.8 with confidence intervals), and NNT of 5.4 (3.5 to 12 with confidence intervals) for 400mg ibuprofen compared with the combination. (2) The relative benefit of the combination treatment compared with ibuprofen alone was 1.3 (1.1 to 1.3). 151 Reckitt noted the following matters concerning this review: (1) The study tested combination analgesics that contained different amounts of paracetamol and ibuprofen as compared to Maxigesic. The three combination analgesics in question contained: (a) ibuprofen 200mg and paracetamol 500mg (compared against placebo); (b) ibuprofen 400mg and paracetamol 1000mg (compared against placebo); and (c) ibuprofen 400mg and paracetamol 1000mg (compared against ibuprofen 400mg). (2) The "primary outcome" for the review was "[p]articipants achieving at least 50% of maximum pain relief over 4 to 6 hours". (3) The review did not analyse time to onset of pain relief. 152 Reckitt relied on Dr Russo's acceptance in cross-examination that the Derry review "is not a review that includes data for paracetamol as a monotherapy" and that the "focus there is on ibuprofen monotherapy but not paracetamol" to submit that the conclusion reached in the Derry review, that "ibuprofen plus paracetamol combinations provided better analgesia than either drug alone (at the same dose)" must be understood as a conclusion relating only to ibuprofen, and not paracetamol. 153 AFT contended that the fact that there was no single study in the Derry Review comparing the combination to paracetamol misunderstands the methods employed to prepare a Cochrane review such as the Derry review. AFT noted that Dr Russo was not asked whether this impacted on his ability to rely on the Derry review.

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Daniels 2011 study 154 In the 2018 judgment, I made the following findings concerning the study: [116] The Daniels study assessed the efficacy of single doses of 1000mg paracetamol/400mg ibuprofen and 500mg paracetamol/200mg ibuprofen against 400mg ibuprofen/25.6mg codeine, 1000mg paracetamol/30mg codeine and placebo in a dental pain model of removal of at least three impacted teeth. [117] Under the heading "Discussion", the authors concluded: In conclusion, 1 or 2 tablets of a single-tablet combination of ibuprofen 200mg/paracetamol 500mg provided highly effective analgesia that was comparable with, or superior to, other combination analgesics marketed for strong pain. Paracetamol combined with ibuprofen, at the dose range studied, is a more effective analgesic than codeine combined with ibuprofen. The novel single-tablet combination of ibuprofen/paracetamol would provide a useful alternative analgesic option for people not wishing to take codeine. [118] As AFT contended, the Daniels Study concluded that: (1) 1000mg paracetamol/400mg ibuprofen was significantly more efficacious than 500mg paracetamol/200mg ibuprofen. The precise finding was that "[t]wo tablets of the single-tablet combination of ibuprofen 200mg/paracetamol 500mg were statistically significantly more efficacious than 1 tablet of the single-tablet combination". (2) "The pain relief scores over time curves ... illustrate that the peak pain relief was higher and sustained for longer with 2 tablets of the single tablet combination of ibuprofen/paracetamol compared with all other treatments". [119] Reckitt contended that the Daniels study made no comparative finding as to a statistically significant difference between 500mg paracetamol/200mg ibuprofen and 1000mg paracetamol/400mg ibuprofen over a single 8 hour dose. Under the heading "primary efficacy endpoint', the authors states: The results of all 5 planned primary comparisons were positive for both 1 and 2 tablets of the single-tablet combination of ibuprofen 200mg/paracetamol 500mg compared with the other treatments. [120] However, the statements identified by AFT do appear to me to be comparative findings. There is also a finding that "2 tablets of the single-tablet combination of ibuprofen 200mg/paracetamol 500mg provided significantly more pain relief than 1 tablet from 5 hours onwards". [121] Thus, in my view, the Daniels study provides scientific evidence that a combination of 1000mg paracetamol/400mg ibuprofen is a more effective dose than 500mg paracetamol/200mg ibuprofen. It does not provide scientific evidence that a combination of 1000mg paracetamol/300mg ibuprofen (that is, a combination containing less ibuprofen) is a more effective dose than 500mg paracetamol/200mg ibuprofen, because it did not test that comparison. 155 AFT submitted that the Daniels 2011 study concluded that: (1) 1000mg paracetamol/400mg ibuprofen was significantly more efficacious than 500mg paracetamol/200mg ibuprofen and the monotherapies in combination with codeine; (2) a combination of 1000mg paracetamol/400mg ibuprofen provided faster onset of pain relief than a combination of 500mg paracetamol/200mg ibuprofen and the monotherapies in combination with codeine. 156 As Reckitt noted, this study compared two paracetamol/ibuprofen combinations as against other combination analgesics, rather than against paracetamol or ibuprofen alone. 157 AFT's written submissions did not explain how this study supported the statements and representations at issue in this proceeding, which involve comparisons between Maxigesic and two monotherapies. 158 Dr Russo expressed the view that the Daniels 2011 study demonstrated that: [I]n the 12 hour study period the combination of 1000mg paracetamol/400mg ibuprofen provides: … (c) faster onset of pain relief (measured by the secondary endpoint of median time to pain half gone of 30 minutes), compared to: (i) 44 minutes for 500mg paracetamol/200mg ibuprofen; (ii) 45 minutes for two tablets of 200mg ibuprofen/12.8mg codeine; (iii) 45 minutes for two tablets of 500mg paracetamol/15mg codeine; and (iv) 300 minutes for placebo. 159 I do not accept Dr Russo's evidence, set out at [132] above, that the Daniels 2011 study "demonstrated that faster onset of meaningful pain relief is more likely to be achieved with the combination as against the monotherapies, as determined using the two-stopwatch method to measure time to meaningful pain relief" without more explanation, for the following two reasons: (1) the study did not test the performance of either paracetamol or ibuprofen as a monotherapy; and (2) the study publication's description of the study does not refer to testing for meaningful pain relief using the two-stopwatch method. 160 However, I do accept Dr Russo's evidence that the Daniels 2011 study was one of several studies that "contribute to the wider body of scientific literature relating to combination analgesics".

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Mehlisch No. 1 study 162 In the 2018 judgment, I made the following findings concerning the study: [128] The Mehlisch No. 1 study compared the pain relief provided to patients undergoing the removal of three to four impacted molars by a single dose of paracetamol (1000mg and 500mg), a single dose of ibuprofen (400mg and 200mg) and combinations of the two monotherapies (1000mg paracetamol/400mg ibuprofen and 500mg paracetamol/200mg ibuprofen). [129] The authors noted: One of the main objectives of this proof-of-concept study was to test the hypothesis that combination therapy with ibuprofen and paracetamol would be more effective than either agent alone when used at their maximum licensed over-the-counter doses, as stipulated by regulatory authorities in the United States. [130] The authors also referred to the study as a "pilot study". There were 234 patients in the intent-to-treat population. [131] The authors noted that "doses of ibuprofen and paracetamol were selected to be at or near their analgesic ceiling in relation to their respective dose-response curves". [132] The study's conclusions included that: (1) 1000mg paracetamol/400mg ibuprofen provided significantly better mean pain relief than 500mg paracetamol/200mg ibuprofen, with the authors noting that "[a] dose-response effect for SPRID8 [Sum of Pain Relief and pain Intensity Differences from base line (0 hour) to 8 hours after dosing] was observed with combination therapy; (2) ibuprofen 400mg/paracetamol 1000mg was ~30% more effective than ibuprofen 200mg/paracetamol 500mg"; (3) 1000mg paracetamol/400mg ibuprofen provided a higher peak mean pain relief score than 500mg paracetamol/200mg ibuprofen, which was significant at 4 hours;"[at] most time points, patients in the ibuprofen 400mg/paracetamol 1000mg group achieved significantly better mean PID [Pain Intensity Difference] scores than ibuprofen alone, paracetamol alone, and ibuprofen 200mg/paracetamol 500mg"; and (4) 1000mg paracetamol/400mg ibuprofen provided superior pain relief to 400mg ibuprofen whereas 500mg paracetamol/200mg ibuprofen did not. [133] Reckitt noted that 1000mg paracetamol/400mg ibuprofen was found to be no different in efficacy between zero and four hours, compared to the 200mg/500mg combination. Accordingly, Reckitt submitted, there was no better pain relief, at all, over that four hours, between 500mg paracetamol/200mg ibuprofen and 1000mg paracetamol/400mg ibuprofen. As such, Reckitt argued, the Mehlisch No. 1 study provides no basis for any comparison between Maxigesic and any other combination analgesic and furthermore provides no basis for any assertion of superiority of Maxigesic (single dose duration six hours) over one tablet of Nuromol (single dose duration eight hours) in circumstances where there was no difference in efficacy between 500mg paracetamol/200mg ibuprofen and 1000mg paracetamol/400mg ibuprofen over the first four hours. [134] Accepting Reckitt's qualifications set out above, the Mehlisch No. 1 study provides scientific evidence that a combination of 1000mg paracetamol/400mg ibuprofen is a more effective dose than 500mg paracetamol/200mg ibuprofen. 163 AFT noted the observation, in the discussion of the Mehlisch No. 1 study, that: The results indicated that of the 4 active treatment arms, ibuprofen 400 mg/paracetamol 1000 mg provided significantly better analgesic efficacy than ibuprofen 400 mg alone and paracetamol 1000 mg alone on virtually every outcome measure, including the primary end point. Although ibuprofen 400 mg/paracetamol 1000 mg was also significantly better than ibuprofen 200 mg/paracetamol 500 mg on a number of efficacy end points, the lower-dose combination was nonetheless often more effective than both ibuprofen 400 mg alone and paracetamol 1000 mg alone. 164 Dr Russo expressed his own opinion as to what was demonstrated by the study "in the eight hour study period", including that: (1) 500mg paracetamol/200mg ibuprofen provided superior analgesic efficacy than 1000mg paracetamol alone and possible superior analgesic efficacy than 400mg ibuprofen alone; and (2) 1000mg paracetamol/400mg ibuprofen likely provided superior analgesic efficacy than 500mg paracetamol/200mg ibuprofen. 165 Dr Russo also expressed the following opinion based on his review of a summary table of the secondary end points used in the study to test comparative speed of onset: Based on my review of these results, I consider that the secondary endpoints of "time to first meaningful pain relief' and "time to pain half gone" are most relevant to assessing speed of analgesia. In this regard, I note that participants in both 1000mg paracetamol/400mg ibuprofen and 500mg paracetamol/200mg ibuprofen arms achieved faster times to first meaningful pain relief and pain half gone than ibuprofen 400mg, paracetamol 1000mg and placebo. Accordingly, I consider that the combination treatments will likely provide faster pain relief than either paracetamol or ibuprofen. 166 Reckitt made the following observations concerning the study: The Mehlisch No 1 Study was a "proof of concept" study for the Mehlisch No 2 Study. A proof of concept study is conducted to test whether the next cycle of investment is justified. Thus the Mehlisch No 1 Study had only 234 patients, whereas the later Mehlisch No 2 Study had 735 patients. Neither study analysed Maxigesic or a combination analgesic with the same formulation as Maxigesic. Neither study analysed any comparison between a combination analgesic and the monotherapies beyond eight hours. Neither study provides any data about Maxigesic or any data about analgesic efficacy after eight hours. … AFT claim that Mehlisch No 1 concluded that 1000mg paracetamol/400mg ibuprofen and 500mg paracetamol/200mg ibuprofen achieved faster times to meaningful pain relief than ibuprofen and paracetamol alone. However they failed to mention the results for the 1000mg paracetamol/400mg ibuprofen comparison to the monotherapies were not statistically significant and neither was the 500mg paracetamol/200mg ibuprofen comparison for ibuprofen alone.

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Mehlisch No. 2 study 167 In the 2018 judgment, I made the following relevant findings: [135] The Mehlisch No. 2 study was two stage clinical trial that was designed to confirm and extend the findings of the Mehlisch No. 1 study and to generate data for regulatory purposes. A total of 735 patients were randomly assigned in stage one and 715 entered and 678 completed stage two. [136] The report of the study described its objectives as follows: This study was a 2-stage clinical trial that was designed to confirm and extend the findings of the earlier study in the same dental plain model and to generate data for regulatory purposes. The objective of stage 1 was to compare the efficacy and tolerability of 3 doses of a single-tablet fixed-dose combination (FDC) of ibuprofen and paracetamol (ibuprofen 100 mg/paracetamol 250 mg, ibuprofen 200 mg/paracetamol 500 mg, and ibuprofen 400 mg/paracetamol 10000 mg) with comparable doses of ibuprofen monotherapy, paracetamol monotherapy, and placebo. In addition, and from a clinical dosing standpoint, it was of interest to compare results for the FDC ibuprofen 200 mg/paracetamol 500 mg with ibuprofen 400 mg alone and paracetamol 1000 mg alone. The objective of stage 2 was to compare the efficacy and tolerability of the same 3 doses of the FDC with each other and with placebo over the 72 hour postoperative period following stage 1. [137] The stated conclusion of the report was: FDC ibuprofen 200 mg/paracetamol 500mg and ibuprofen 400 mg/paracetamol 1000 mg were significantly more effective in this population than were comparable doses of ibuprofen or paracetamol alone in moderate to severe acute dental pain and were significantly more effective than placebo in providing sustained pain relief. [138] The Mehlisch No. 2 study (a) did not find a statistically significant difference between 1000mg paracetamol/400mg ibuprofen and 500mg paracetamol/200mg ibuprofen, and (b) found that 1000mg paracetamol/400mg ibuprofen was superior to 400mg ibuprofen but that 500mg paracetamol/200mg ibuprofen was not. [139] AFT noted the following observations of the report's authors: The dental pain model is widely used to evaluate the efficacy of analgesic agents such as NSAIDs [Nonsteroidal Anti-inflammatory Drugs] and paracetamol ... The dental pain model has a proven record of assay sensitivity in separating active drugs from each other and from placebo and has the potential to demonstrate additional pain relief with combination therapy (ie, upside model sensitivity). 168 AFT referred to the conclusion set out at [137] of the 2018 judgment. AFT also referred to the following statement in the study: Overall, analgesia had a faster onset, was more effective, and had a longer duration with the FDC regimens than with monotherapy or placebo in the immediate post-operative period (stage 1). 169 Based on his review of the secondary end points result in the study, and relevant discussion in the study publication, Dr Russo's opinion was as follows: I consider that the study provides evidence that 500mg paracetamol/200mg ibuprofen provides faster pain relief than 250mg paracetamol/100mg ibuprofen, 1000mg paracetamol, 400mg ibuprofen and 200mg ibuprofen. This is because the time to meaningful pain relief (based on a Kaplan-Meier median) was the lowest for the 500mg paracetamol/200mg ibuprofen (39.3 minutes) compared with the lower dose combination (45.9 minutes), ibuprofen (70.5 minutes for 400mg and 80.0 minutes for 200mg) and 1000mg paracetamol (45.6 minutes). 170 Reckitt submitted that AFT did not dispute that of the six time to pain relief measurements reported, none of the results were statistically significant in respect of the combination versus paracetamol except for time to meaningful pain relief.

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Ong review (2010) 171 The Ong review, entitled "Combining paracetamol (Acetaminophen) with Nonsteroidal Antiinflammatory Drugs: A Qualitative Systematic Review of Analgesic Efficacy for Acute Postoperative Pain", was a systematic review of literature from 1988 to 2009 of 32 randomised controlled trials that compared combinations of paracetamol with various NSAIDs versus at least one of these constituent drugs. The review states the following conclusion: "Current evidence suggests that a combination of paracetamol and an NSAID may offer superior analgesic compared with either drug alone." 172 Dr Russo stated that the Ong review reported the following: (a) In 17 out of 20 studies (~85%) comparing NSAIDs / paracetamol combinations against paracetamol alone, the combination "was more effective than paracetamol alone in terms of lower pain scores, lower supplemental analgesic requirements, or better globally assessed pain relief (positive studies)." (see page 1171 ). (b) NSAID / paracetamol combinations were more effective than paracetamol in 4 out of 5 studies involving the dental pain model (see page 1171). (c) In 9 out of 14 studies (~64%) comparing NSAIDs / paracetamol combinations against NSAID alone, the combination "more effective than an NSAID alone in terms of lower pain scores, lower supplemental analgesic requirements, or better globally assessed pain relief for the combination group" (see page 1174). (d) NSAID / paracetamol combinations were more effective than NSAID alone in 3 out of 4 studies involving the dental pain model (see page 1171). 173 Dr Russo expressed the view that the Ong review "indicates … that there is highly likely a "class response" in terms of the superior analgesic efficacy of NSAIDs (as a class of drugs) when combined with paracetamol, over their individual constituents. 174 Reckitt noted the following concerning the review: (1) The review was a literature review and the authors noted that its "limitations" included: (a) its "qualitative approach"; (b) "the wide range of acute pain models included in the studies reviewed"; and (c) the fact that "[a] quantitative meta-analysis" was not possible for the studies reviewed "because of heterogeneity of study design". Dr Russo acknowledged these matters in cross-examination. (2) Only three of three trials considered by the review compared a paracetamol/ibuprofen combination to ibuprofen alone: the Dahl, Menhinick and Viitanen studies. Of these: (a) the Dahl Study showed "no difference in outcome measures" (i.e. pain scores and supplemental analgesic requirements) as between the combination analgesic and ibuprofen alone; (b) the Menhinick study is not relied upon by AFT except as "early research" indicating that combination analgesics are likely to provide better analgesia than individual drugs; and (c) the Viitanen study considered single rectal doses of the study drugs in relation to paediatric tonsillectomy.

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Maxigesic provides better pain relief 176 AFT argued that there is an adequate scientific foundation for its claims about better pain relief for the following three reasons: (1) The primary end point of the Daniels 2018 study (SPID48) provides a foundation for these claims. Ultimately, there appeared to be little dispute about this among the experts. The SPID6 results reported in the Daniels 2018 study also provide support these claims. Further, several of the secondary end points of the Daniels 2018 study, including mean consumption of rescue medication (mg) and percentage of patients requiring rescue medication, provide further support for the claims. The results of the Daniels 2018 study can be read directly on to Maxigesic. There is common ground between the experts that, to the extent that the fasted Cmax difference is of any relevance, its relevance would bear upon to the time to perceptible pain relief, rather than the extent of relief. That does not concern the primary end point or AFT's claims in the new advertisement insofar as they claim "better" relief. (2) The wider body of scientific literature provides strong support for the conclusion that the combination of 400mg ibuprofen/1000mg paracetamol will provide better pain relief than 400mg ibuprofen or 1000mg paracetamol as monotherapies. (3) Insofar as the claims refer to Maxigesic being 36% more effective than ibuprofen and 78% more effective than paracetamol, those claims are based on the primary end point of the Daniels 2018 study and the derivation of the percentages is a matter of mathematics. The percentages are not to be understood as absolute figures, but rather the percentages achieved in the Daniels 2018 study itself. It can be recognised that a different study may achieve different percentages, but that is not the point. 177 As to the first point, the experts' agreement is more specific than AFT acknowledges. The agreed statement was: 45. We agree that the Daniels Study demonstrated better pain relief, as measured by the SPID48, for the Daniels FDC as compared to equivalent amounts of each of the monotherapies, each delivered as three tablets every 6 hours. The Daniels FDC produced greater cumulative pain relief by 6 hours (SPID6) than either paracetamol or ibuprofen produced by 48 hours (SPID48). 178 The new advertisement can be read as a set of claims about the results of the Daniels 2018 study. As I understood the evidence of Dr Russo and Professor Thisted, each of them read the advertisement in that manner. I accept that a reasonable reader may read the new advertisement in that way, particularly because of the extensive use of footnotes and the reference, in the body of the advertisement, to a "new clinical study of moderate to severe dental pain" which "shows that Maxigesic provides better and faster pain relief …". On that reading of the new advertisement, I accept, for example, that the primary end point of the Daniels 2018 study (SPID48) provides a foundation for the claim that Maxigesic provides better pain relief than paracetamol or ibuprofen alone. On that reading, it is implicit that the claim of better pain relief is limited to better pain relief as measured by the Daniels 2018 study, extrapolated onto Maxigesic on the basis of the Aitken study. 179 However, the case proceeded on the basis that the advertising materials conveyed much broader representations. For example, the first agreed representation, that Maxigesic is more efficacious than paracetamol or ibuprofen alone, is unrestricted as to the nature of the pain treated, the dosage of the drugs taken and the duration of treatment. There was no expert evidence that the results of the Daniels 2018 study could be extrapolated to an unqualified statement that Maxigesic is more efficacious than paracetamol or ibuprofen alone in all contexts. To the contrary, the experts agreed that the Daniels 2018 study is not directly informative concerning degree of pain relief in contexts other than the acute pain dental impaction setting. The experts also agreed that one cannot extrapolate effectiveness in pain control from acute pain models, such as was used in the Daniels 2018 study, to chronic pain settings. 180 Similarly, neither the experts collectively, nor Dr Russo individually, gave evidence that the implications of the wider body of scientific literature are as far reaching as AFT now contends. The broadest statement is in the Acute Pain Management text but, on closer examination, that does not support an unqualified claim that Maxigesic provides better pain relief than either paracetamol or ibuprofen alone. 181 As to the claims referring to Maxigesic being 36% more effective than ibuprofen and 78% more effective than paracetamol, I accept that those claims are based on the primary end point of the Daniels 2018 study and the derivation of the percentages is a matter of mathematics. 182 However, since the Daniels FDC contained different quantities of paracetamol and ibuprofen from Maxigesic, the relative effectiveness of Maxigesic to corresponding treatment with ibuprofen and paracetamol separately cannot be assumed to match the figures for the Daniels FDC. Professor Keech's view that the true numbers would be different by an unknown amount, even though we would expect them to be very similar. Professor Thisted agreed that the results would not be identical if the Daniels 2018 study was replicated using Maxigesic, but held "that the percentage differences in pain relief should be substantially similar and the 36% and 78% figures would not misrepresent them".

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Maxigesic provides faster pain relief 183 AFT relied on the following two matters to support its contention that there is an adequate scientific foundation for its claims about faster pain relief: (1) the secondary end point of the Daniels 2018 study of median time to meaningful pain relief; and (2) the wider body of scientific literature, in particular, the Mehlisch studies and the Daniels 2011 study. 184 AFT relied on Dr Russo's evidence that, from a clinical perspective, time to meaningful pain relief is relevant rather than time to perceptible pain relief. The significance of this observation was that the Daniels 2018 study did not report statistically significant results in favour of the Daniels FDC for the following end points: (a) time to perceptible pain relief; (b) time to peak response; (c) time to perceptible pain relief confirmed by meaningful pain relief; and (d) time to requirement of rescue medication in the first dosing interval. 185 In particular, Dr Russo said: … I disagree that time to perceptible pain relief is the appropriate measure for determining "better and faster"' analgesia. In my view, as I stated above, from a clinical perspective, I am more interested in faster onset of analgesia, meaning that a patient's pain has decreased by a meaningful (and not trivial) amount. This is measured in the Daniels Study by "median time to meaningful pain relief", where [Daniels] FDC outperformed the monotherapies. By contrast, time to perceptible pain relief is merely marking the point at which any differences in the patient's perceptible pain was reported. In my view, this does not provide an accurate picture of the onset or degree of analgesia, and is less clinically significant. 186 AFT also relied upon the following passage of the oral evidence of Dr Russo: MR MURRAY: No. And do you agree that quicker perceptible relief is likely to be desirable? DR RUSSO: Not really, no. MR MURRAY: And that's because in your opinion, it's meaningful relief that's the relevant measure. DR RUSSO: Yes. I mean, when you talk about perceptible pain relief, the instructions - how that's defined is press this button on the stopwatch as soon as you think you can detect any sort of change downwards in your pain at all. MR MURRAY: Yes. DR RUSSO: So typically we've seen in studies that that represents a three per cent to a five per cent reduction that people typically will press the button at. MR MURRAY: Yes. DR RUSSO: So if your pain is eight out of 10 and it then goes to 7.84 out of 10, that is not a meaningful difference that makes any difference to the patient's suffering, for example. You're still in severe pain. So there's a concept of minimum clinically important difference and that is typically defined by a .5 or more reduction on a VAS scale or - or a 30 per cent reduction global pain levels and that is what appears to be significant to patients when you ask their opinion. Doctors typically use 50 per cent, but that turns out to be a conservative measure. And you won't find that with perceptible; you will find that with - when asking people to record their meaningful pain relief or their maximum pain relief. 187 Reckitt submitted that, even without adjustment for multiple hypotheses testing, four of the six secondary end points in the Daniels study that measured the speed of efficacy of the Daniels FDC did not reach statistical significance for one or both of the monotherapies. These secondary end points were: (a) median time to perceptible pain relief; (b) median time to peak response; (c) median time to perceptible pain relief confirmed by meaningful pain relief; and (d) median time to the requirement of rescue medication within the first dosing interval. 188 Reckitt also argued that, having regard to the identification in the Daniels 2018 study of the "key secondary endpoint" which included time to perceptible pain relief, and the references to the testing of time to perceptible pain relief in the SAP and the study protocol, it is not tenable to dismiss the results on that end point as irrelevant. As Professor Keech put it: … [T]o the extent that a patient is given an analgesic product after a wisdom tooth extraction and asks the question, "When is this going to work", then it's obviously relevant as the designers of the study indicated themselves in designing it as a secondary [end point]. 189 I am satisfied that the Daniels 2018 study secondary end point of median time to meaningful pain relief provides an adequate scientific foundation for the statement that Maxigesic provides "Faster onset of meaningful pain relief than for paracetamol or ibuprofen alone", where it is implicit that the statement is limited to speed of onset as measured by the Daniels 2018 study, extrapolated onto Maxigesic on the basis of the Aitken study. 190 Otherwise, I am not satisfied that the single secondary end point provides an adequate scientific foundation for a claim of faster pain relief because the Daniels FDC results did not achieve statistical significance for all secondary end points related to time to pain relief. 191 As to the wider body of scientific literature, I am not satisfied that the Daniels 2011 study supports a claim that Maxigesic provides faster pain relief than either paracetamol or ibuprofen because that study did not assess the comparative efficacy of either paracetamol or ibuprofen as a monotherapy. 192 I am not satisfied that the Mehlisch No. 1 study supports a claim to this effect for the reasons identified by Reckitt, that is, it studies different formulations of the combination analgesic (1000mg paracetamol/400mg ibuprofen and 500mg paracetamol/200mg ibuprofen) and the results for time to pain relief included results that lacked statistical significance. 193 I am also not satisfied that the Mehlisch No. 2 study supports a claim to this effect because it studies different formulations of the combination analgesic and again because the results for time to pain relief included results that lacked statistical significance.

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Conclusions about representations 197 On the basis of the findings set out above, the following unqualified representations do not have an adequate scientific foundation: (1) Maxigesic is more efficacious than paracetamol or ibuprofen alone; (2) Maxigesic provides better and faster pain relief than both paracetamol or ibuprofen alone; (3) Maxigesic provides better and faster pain relief than both paracetamol or ibuprofen alone at maximum dosage; (4) Maxigesic provides 36% more effective pain relief than ibuprofen and 78% more effective pain relief than paracetamol; and (5) Maxigesic provides better pain relief than paracetamol and ibuprofen alone. 198 The reason for these conclusions is that each of the representations is unlimited as to nature of pain, dosage and treatment duration. As explained above, the scientific evidence is addressed to much more specific comparisons and the expert evidence does not support a conclusion that there is an adequate scientific basis for extrapolating from the Daniels 2018 study and the wider body of scientific evidence to the unqualified representations. Even the evidence of Dr Russo and Professor Thisted, that the Daniels 2018 study provides an adequate scientific foundation for the statements in the new advertisement, must be understood in the context of their agreement that the study is not directly informative concerning degree of pain relief in contexts other than the acute pain dental impaction setting. As I understood their evidence on this point, it was predicated upon an assumption that the claims in the advertisement are addressed to the treatment of acute pain. 199 Further, there is no adequate scientific foundation for making the restrained representation. 200 It follows that the five representations listed above are misleading or deceptive or likely to mislead or deceive. By making those representations in the new advertisement, and to the extent that there has been any publication of the training aid or the POS materials, AFT has engaged in conduct in contravention of ss 18, 29(1)(g) and 33 of the Australian Consumer Law. 201 By making the restrained representation in the new advertisement, AFT has breached order 12 of the orders made on 29 November 2018.

AFT Pharmaceuticals (AU) Pty Ltd v Reckitt Benckiser

At a glance

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Judgment (44 paragraphs)

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Cases Cited (23)

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